Section IV - Metabolic Liver Disease

Eminoglu, TF, et al. Very long-chain acyl CoA dehydrogenase deficiency which was accepted as infanticide. Forensic Sci Int 2011;210(1–3):e1–3.CrossRefGoogle ScholarPubMed

Saudubray, JM,(2016). Clinical approach to inborn errors of metabolism in pediatrics. In Saudubray, JM, Walter, JH (Eds.), Inborn Metabolic Diseases: Diagnosis and Treatment (pp. 3–69). New York: Springer Berlin Heidelberg.CrossRefGoogle Scholar

Blau, N, Duran, M, Gibson, KM. (2008). Laboratory Guide to the Methods in Biochemical Genetics (pp. xxvi, 860). Berlin: Springer.CrossRefGoogle Scholar

Crushell, E, et al. Negative screening tests in classical galactosaemia caused by S135L homozygosity. J Inherit Metab Dis 2009;32(3):412–15.CrossRefGoogle ScholarPubMed

Vilarinho, S, Mistry, PK. Exome sequencing in clinical hepatology. Hepatology 2019;70(6):2185–92.CrossRefGoogle ScholarPubMed

Hegarty, R, et al. Inherited metabolic disorders presenting as acute liver failure in newborns and young children: King’s College Hospital experience. Eur J Pediatr 2015;174(10):1387–92.CrossRefGoogle Scholar

Li, H, et al. Acute liver failure in neonates with undiagnosed hereditary fructose intolerance due to exposure from widely available infant formulas. Mol Genet Metab 2018;123(4):428–32.CrossRefGoogle ScholarPubMed

Chinsky, JM, et al. Diagnosis and treatment of tyrosinemia type I: a US and Canadian consensus group review and recommendations. Genet Med 2017;19(12). Doi: 10.1038/gim.2017.101CrossRefGoogle Scholar

Heissat, S, et al. Neonatal hemochromatosis: diagnostic work-up based on a series of 56 cases of fetal death and neonatal liver failure. J Pediatr 2015;166(1):66–73.CrossRefGoogle ScholarPubMed

Salen, G, Steiner, RD. Epidemiology, diagnosis, and treatment of cerebrotendinous xanthomatosis (CTX). J Inherit Metab Dis 2017;40(6):771–81.CrossRefGoogle Scholar

Bull, LN, Thompson, RJ. Progressive familial intrahepatic cholestasis. Clin Liver Dis 2018;22(4):657–69.CrossRefGoogle ScholarPubMed

Gheldof, A, et al. Clinical implementation of gene panel testing for lysosomal storage diseases. Mol Genet Genomic Med 2019;7(2):e00527.CrossRefGoogle ScholarPubMed

Walter, J, Laforêt, L.P. (2016). The glycogen storage diseases and related disorders. In Saudubray, BM, Walter, J (Eds.), Inborn Metabolic Diseases: Diagnosis and Treatment (pp. 121–37). New York: Springer Berlin Heidelberg.Google Scholar

Frazier, DM, et al. The tandem mass spectrometry newborn screening experience in North Carolina: 1997–2005. J Inherit Metab Dis 2006;29(1):76–85.CrossRefGoogle ScholarPubMed

Matern, D. (2008). Acylcarnitines, including in vitro loading tests. In Blau, N (Ed.), Laboratory Guide to the Methods in Biochemical Genetics (pp. 171–206). Berlin: Springer-Verlag.CrossRefGoogle Scholar

Rinaldo, P. (2008). Organic acids. In Blau, DM, Gibson, KM (Eds.), Laboratory Guide to the Methods in Biochemical Genetics pp. (137–70). Berlin: Springer-Verlag.Google Scholar

Vassault, A. (2008). Lactate, pyruvate, acetoacetate and 3-hydroxybutyrate. In Blau, DM, Gibson, KM (Eds.), Laboratory Guide to the Methods in Biochemical Genetics (pp. 35–51). Berlin: Springer-Verlag.CrossRefGoogle Scholar

Coude, FX, et al. Secondary citrullinemia with hyperammonemia in four neonatal cases of pyruvate carboxylase deficiency. Pediatrics 1981;68(6):914.Google ScholarPubMed

Munnich, A, et al. Congenital lactic acidosis, alpha-ketoglutaric aciduria and variant form of maple syrup urine disease due to a single enzyme defect: dihydrolipoyl dehydrogenase deficiency. Acta Paediatr Scand 1982;71(1):167–71.CrossRefGoogle ScholarPubMed

Bonnefont, JP, et al. Alpha-ketoglutarate dehydrogenase deficiency presenting as congenital lactic acidosis. J Pediatr 1992;121(2):255–8.CrossRefGoogle ScholarPubMed

da Fonseca-Wollheim, F. Deamidation of glutamine by increased plasma gamma-glutamyltransferase is a source of rapid ammonia formation in blood and plasma specimens. Clin Chem 1990;36(8 Pt 1):1479–82.CrossRefGoogle ScholarPubMed

Tein, I. Neonatal metabolic myopathies. Semin Perinatol 1999;23(2):125–51.CrossRefGoogle ScholarPubMed

Chalmers, RA. Organic acids in urine of patients with congenital lactic acidoses: an aid to differential diagnosis. J Inherit Metab Dis 1984;7(Suppl 1):79–89.CrossRefGoogle ScholarPubMed

Cowan, TM, et al. Technical standards and guidelines for the diagnosis of biotinidase deficiency. Genet Med 2010;12(7):464–70.CrossRefGoogle Scholar

Bourgeron, T, et al. Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency. Nat Genet 1995;11(2):144–9.CrossRefGoogle ScholarPubMed

Bennett, MJ, et al. Secondary inhibition of multiple NAD-requiring dehydrogenases in respiratory chain complex I deficiency: possible metabolic markers for the primary defect. J Inherit Metab Dis 1993;16(3):560–2.CrossRefGoogle ScholarPubMed

Kerner, J, Hoppel, C. Fatty acid import into mitochondria. Biochim Biophys Acta 2000;1486(1):1–17.CrossRefGoogle ScholarPubMed

Rinaldo, P, et al. Sudden neonatal death in carnitine transporter deficiency. J Pediatr 1997;131(2):304–5.CrossRefGoogle ScholarPubMed

Raymond, K, et al. Medium-chain acyl-CoA dehydrogenase deficiency: sudden and unexpected death of a 45 year old woman. Genet Med 1999;1(6):293–4.CrossRefGoogle ScholarPubMed

Patel, JS, Leonard, JV. Ketonuria and medium-chain acyl-CoA dehydrogenase deficiency. J Inherit Metab Dis 1995;18(1):98–9.CrossRefGoogle ScholarPubMed

Rinaldo, P, et al. Clinical and biochemical features of fatty acid oxidation disorders. Curr Opin Pediatr 1998;10(6):615–21.CrossRefGoogle ScholarPubMed

Burrage, LC, et al. Elevations of C14:1 and C14:2 plasma acylcarnitines in fasted children: a diagnostic dilemma. J Pediatr 2016;169:208–13 e2.CrossRefGoogle ScholarPubMed

Costa, CC, et al. Dynamic changes of plasma acylcarnitine levels induced by fasting and sunflower oil challenge test in children. Pediatr Res 1999;46(4):440–4.CrossRefGoogle ScholarPubMed

Drousiotou, A, et al. Ethylmalonic encephalopathy: application of improved biochemical and molecular diagnostic approaches. Clin Genet 2011;79(4):385–90.CrossRefGoogle ScholarPubMed

Stanley, CA, et al. Chronic cardiomyopathy and weakness or acute coma in children with a defect in carnitine uptake. Ann Neurol 1991;30(5):709–16.CrossRefGoogle ScholarPubMed

Minkler, PE, et al. Quantification of carnitine and acylcarnitines in biological matrices by HPLC electrospray ionization-mass spectrometry. Clin Chem 2008;54(9):1451–62.CrossRefGoogle ScholarPubMed

Boles, RG, et al. Retrospective biochemical screening of fatty acid oxidation disorders in postmortem livers of 418 cases of sudden death in the first year of life. J Pediatr 1998;132(6):924–33.CrossRefGoogle ScholarPubMed

Dietzen, DJ, et al. National academy of clinical biochemistry laboratory medicine practice guidelines: follow-up testing for metabolic disease identified by expanded newborn screening using tandem mass spectrometry; executive summary. Clin Chem 2009;55(9):1615–26.CrossRefGoogle ScholarPubMed

Ohura, T, et al. Clinical pictures of 75 patients with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). J Inherit Metab Dis 2007;30(2):139–44.CrossRefGoogle Scholar

Saheki, T, Song, YZ. (1993). Citrin deficiency. In Adam, MP et al. (Eds.), GeneReviews((R)). Seattle, WA.Google Scholar

Matthews, DE, et al. Alloisoleucine formation in maple syrup urine disease: isotopic evidence for the mechanism. Pediatr Res 1980;14(7):854–7.Google ScholarPubMed

Oglesbee, D, et al. Second-tier test for quantification of alloisoleucine and branched-chain amino acids in dried blood spots to improve newborn screening for maple syrup urine disease (MSUD). Clin Chem 2008;54(3):542–9.CrossRefGoogle Scholar

Van Hove, JLK, et al. (1993). Nonketotic hyperglycinemia. In Adam, MP et al. (Eds.), GeneReviews. Seattle, WA.Google ScholarPubMed

Watson, MS, Lloyd-Puryear, MA, Rinaldo, P, Howell, RR. Newborn screening: toward a uniform screening panel and system. Genet Med 2006;8(Suppl 1):1S–252S.CrossRefGoogle Scholar

Turgeon, C, et al. Combined newborn screening for succinylacetone, amino acids, and acylcarnitines in dried blood spots. Clin Chem 2008;54(4):657–64.CrossRefGoogle ScholarPubMed

Tortorelli, S, et al. Two-tier approach to the newborn screening of methylenetetrahydrofolate reductase deficiency and other remethylation disorders with tandem mass spectrometry. J Pediatr 2010;157(2):271–5.CrossRefGoogle ScholarPubMed

Turgeon, CT, et al. Determination of total homocysteine, methylmalonic acid, and 2-methylcitric acid in dried blood spots by tandem mass spectrometry. Clin Chem 2010;56(11):1686–95.CrossRefGoogle ScholarPubMed

McHugh, D, et al. Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: a worldwide collaborative project. Genet Med 2011;13(3):230–54.CrossRefGoogle ScholarPubMed

Marquardt, G, et al. Enhanced interpretation of newborn screening results without analyte cutoff values. Genet Med 2012;14(7):648–55.CrossRefGoogle ScholarPubMed

Calonge, N, et al. Committee report: method for evaluating conditions nominated for population-based screening of newborns and children. Genet Med 2010;12(3):153–9.CrossRefGoogle ScholarPubMed

Sveger, T. Liver disease in alpha1-antitrypsin deficiency detected by screening of 200,000 infants. N Engl J Med 1976;294:1316–21.CrossRefGoogle ScholarPubMed

Silverman, EK, Sandhaus, RA. Clinical practice. Alpha1-antitrypsin deficiency. N Engl J Med 2009;360: 2749–57.CrossRefGoogle ScholarPubMed

Perlmutter, DH. (2011). Alpha-1-antitrypsin deficiency. In Schiff, ER SM, Maddrey, WC (Eds.), Schiff’s Diseases of the Liver, 11th edn., (pp. 835–67). Oxford: Wiley-Blackwell.Google Scholar

Crystal, RG. Alpha 1-antitrypsin deficiency, emphysema, and liver disease. Genetic basis and strategies for therapy. J Clin Invest 1990;85:1343–52.Google ScholarPubMed

Carlson, JA, Rogers, BB, Sifers, RN, Finegold, MJ, Clift, SM, DeMayo, FJ, Bullock, DW, et al. Accumulation of PiZ alpha 1-antitrypsin causes liver damage in transgenic mice. J Clin Invest 1989;83:1183–90.CrossRefGoogle ScholarPubMed

Dycaico, MJ, Grant, SG, Felts, K, Nichols, WS, Geller, SA, Hager, JH, Pollard, AJ, et al. Neonatal hepatitis induced by alpha 1-antitrypsin: a transgenic mouse model. Science 1988;242:1409–12.CrossRefGoogle ScholarPubMed

Hidvegi, T, Ewing, M, Hale, P, Dippold, C, Beckett, C, Kemp, C, Maurice, N, et al. An autophagy-enhancing drug promotes degradation of mutant alpha1-antitrypsin Z and reduces hepatic fibrosis. Science 2010;329:229–32.CrossRefGoogle Scholar

Marcus, NY, Brunt, EM, Blomenkamp, K, Ali, F, Rudnick, DA, Ahmad, M, Teckman, JH. Characteristics of hepatocellular carcinoma in a murine model of alpha-1-antitrypsin deficiency. Hepatol Res 2010;40:641–53.CrossRefGoogle Scholar

Janus, ED, Phillips, NT, Carrell, RW. Smoking, lung function, and alpha 1-antitrypsin deficiency. Lancet 1985;1:152–4.Google ScholarPubMed

Silverman, EK, Province, MA, Rao, DC, Pierce, JA, Campbell, EJ. A family study of the variability of pulmonary function in alpha 1-antitrypsin deficiency. Quantitative phenotypes. Am Rev Respir Dis 1990;142:1015–21.Google ScholarPubMed

Crystal, RG. Augmentation treatment for alpha1 antitrypsin deficiency. Lancet 2015;386:318–20.CrossRefGoogle ScholarPubMed

McElvaney, NG, Burdon, J, Holmes, M, Glanville, A, Wark, PA, Thompson, PJ, Hernandez, P, et al. Long-term efficacy and safety of alpha1 proteinase inhibitor treatment for emphysema caused by severe alpha1 antitrypsin deficiency: an open-label extension trial (RAPID-OLE). Lancet Respir Med 2017;5:51–60.CrossRefGoogle Scholar

Wang, Y, Perlmutter, DH. Targeting intracellular degradation pathways for treatment of liver disease caused by alpha1-antitrypsin deficiency. Pediatr Res 2014;75:133–9.CrossRefGoogle ScholarPubMed

Teckman, JH, Qu, D, Perlmutter, DH. Molecular pathogenesis of liver disease in alpha1-antitrypsin deficiency.Hepatology 1996;24:1504–16.Google ScholarPubMed

Eriksson, S, Carlson, J, Velez, R. Risk of cirrhosis and primary liver cancer in alpha 1-antitrypsin deficiency. N Engl J Med 1986;314:736–9.CrossRefGoogle ScholarPubMed

Zhou, H, Fischer, HP. Liver carcinoma in PiZ alpha-1-antitrypsin deficiency. Am J Surg Pathol 1998;22:742–8.CrossRefGoogle ScholarPubMed

Mostafavi, B, Diaz, S, Tanash, HA, Piitulainen, E. Liver function in alpha-1-antitrypsin deficient individuals at 37 to 40 years of age. Medicine 2017;96:e6180.CrossRefGoogle ScholarPubMed

Sveger, T. The natural history of liver disease in alpha 1-antitrypsin deficient children. Acta Paediatr Scand 1988;77:847–51.CrossRefGoogle ScholarPubMed

Chu, AS, Chopra, KB, Perlmutter, DH. Is severe progressive liver disease caused by alpha-1-antitrypsin deficiency more common in children or adults? Liver Transpl 2016;22:886–94.CrossRefGoogle ScholarPubMed

Volpert, D, Molleston, JP, Perlmutter, DH. Alpha1-antitrypsin deficiency-associated liver disease progresses slowly in some children. J Pediatr Gastroenterol Nutr 2000;31:258–63.CrossRefGoogle ScholarPubMed

Schaefer, B, Mandorfer, M, Viveiros, A, Finkenstedt, A, Ferenci, P, Schneeberger, S, Tilg, H, et al. Heterozygosity for the alpha-1-antitrypsin Z allele in cirrhosis is associated with more advanced disease. Liver Transpl 2018;24:744–51.CrossRefGoogle Scholar

Piitulainen, E, Carlson, J, Ohlsson, K, Alpha, Sveger T. 1-antitrypsin deficiency in 26-year-old subjects: lung, liver, and protease/protease inhibitor studies. Chest 2005;128:2076–81.CrossRefGoogle ScholarPubMed

Teckman, JH, Perlmutter, DH. Retention of mutant alpha(1)-antitrypsin Z in endoplasmic reticulum is associated with an autophagic response. Am J Physiol Gastrointest Liver Physiol 2000;279:G961–74.CrossRefGoogle Scholar

von Schonfeld, J, Breuer, N, Zotz, R, Liedmann, H, Wencker, M, Beste, M, Konietzko, N, et al. Liver function in patients with pulmonary emphysema due to severe alpha-1-antitrypsin deficiency (Pi ZZ). Digestion 1996;57:165–9.Google Scholar

Tomashefski, JF Jr., Crystal, RG, Wiedemann, HP, Mascha, E, Stoller, JK. Alpha 1-Antitrypsin Deficiency Registry Study Group. The bronchopulmonary pathology of alpha-1 antitrypsin (AAT) deficiency: findings of the Death Review Committee of the National Registry for Individuals with Severe Deficiency of Alpha-1 Antitrypsin. Hum Pathol 2004;35:1452–61.CrossRefGoogle Scholar

Corley, M, Solem, A, Phillips, G, Lackey, L, Ziehr, B, Vincent, HA, Mustoe, AM, et al. An RNA structure-mediated, posttranscriptional model of human alpha-1-antitrypsin expression. Proc Natl Acad Sci U S A 2017;114:E10244–E10253.CrossRefGoogle ScholarPubMed

Owen, MC, Brennan, SO, Lewis, JH, Carrell, RW. Mutation of antitrypsin to antithrombin. alpha 1-antitrypsin Pittsburgh (358 Met leads to Arg), a fatal bleeding disorder. N Engl J Med 1983;309:694–8.CrossRefGoogle Scholar

Mast, AE, Enghild, JJ, Nagase, H, Suzuki, K, Pizzo, SV, Salvesen, G. Kinetics and physiologic relevance of the inactivation of alpha 1-proteinase inhibitor, alpha 1-antichymotrypsin, and antithrombin III by matrix metalloproteinases-1 (tissue collagenase), -2 (72-kDa gelatinase/type IV collagenase), and -3 (stromelysin). J Biol Chem 1991;266:15810–16.CrossRefGoogle Scholar

Janoff, A. Elastases and emphysema. Current assessment of the protease-antiprotease hypothesis. Am Rev Respir Dis 1985;132:417–33.Google ScholarPubMed

Ni, K, Serban, KA, Batra, C, Petrache, I. Alpha-1 antitrypsin investigations using animal models of emphysema. Ann Am Thorac Soc 2016;13(Suppl4):S311–16.CrossRefGoogle ScholarPubMed

Borel, F, Sun, H, Zieger, M, Cox, A, Cardozo, B, Li, W, Oliveira, G, et al. Editing out five Serpina1 paralogs to create a mouse model of genetic emphysema. Proc Natl Acad Sci U S A 2018;115:2788–93.CrossRefGoogle ScholarPubMed

Munch, J, Standker, L, Adermann, K, Schulz, A, Schindler, M, Chinnadurai, R, Pohlmann, S, et al. Discovery and optimization of a natural HIV-1 entry inhibitor targeting the gp41 fusion peptide. Cell 2007;129:263–75.CrossRefGoogle ScholarPubMed

Forssmann, WG, The, YH, Stoll, M, Adermann, K, Albrecht, U, Tillmann, HC, Barlos, K, et al. Short-term monotherapy in HIV-infected patients with a virus entry inhibitor against the gp41 fusion peptide. Sci Transl Med 2010;2:63.CrossRefGoogle ScholarPubMed

Janciauskiene, SM, Bals, R, Koczulla, R, Vogelmeier, C, Kohnlein, T, Welte, T. The discovery of alpha1-antitrypsin and its role in health and disease. Respir Med 2011;105:1129–39.CrossRefGoogle ScholarPubMed

Perlmutter, DH, Cole, FS, Kilbridge, P, Rossing, TH, Colten, HR. Expression of the alpha 1-proteinase inhibitor gene in human monocytes and macrophages. Proc Natl Acad Sci U S A 1985;82:795–9.CrossRefGoogle ScholarPubMed

Koopman, P, Povey, S, Lovell-Badge, RH. Widespread expression of human alpha 1-antitrypsin in transgenic mice revealed by in situ hybridization. Genes Dev 1989;3:16–25.CrossRefGoogle ScholarPubMed

Carlson, JA, Rogers, BB, Sifers, RN, Hawkins, HK, Finegold, MJ, Woo, SL. Multiple tissues express alpha 1-antitrypsin in transgenic mice and man. J Clin Invest 1988;82:26–36.CrossRefGoogle ScholarPubMed

Sidhar, SK, Lomas, DA, Carrell, RW, Foreman, RC. Mutations which impede loop/sheet polymerization enhance the secretion of human alpha 1-antitrypsin deficiency variants. J Biol Chem 1995;270:8393–6.CrossRefGoogle ScholarPubMed

Carrell, RW, Lomas, DA. Conformational disease. Lancet 1997;350:134–8.CrossRefGoogle ScholarPubMed

Lomas, DA, Evans, DL, Finch, JT, Carrell, RW. The mechanism of Z alpha 1-antitrypsin accumulation in the liver. Nature 1992;357:605–7.CrossRefGoogle Scholar

Lomas, DA, Elliott, PR, Sidhar, SK, Foreman, RC, Finch, JT, Cox, DW, Whisstock, JC, et al. alpha 1-Antitrypsin Mmalton (Phe52-deleted) forms loop-sheet polymers in vivo. Evidence for the C sheet mechanism of polymerization. J Biol Chem 1995;270:16864–70.Google ScholarPubMed

Lomas, DA, Finch, JT, Seyama, K, Nukiwa, T, Carrell, RW. Alpha 1-antitrypsin Siiyama (Ser53–>Phe). Further evidence for intracellular loop-sheet polymerization. J Biol Chem 1993;268:15333–5.Google Scholar

Curiel, DT, Holmes, MD, Okayama, H, Brantly, ML, Vogelmeier, C, Travis, WD, Stier, LE, et al. Molecular basis of the liver and lung disease associated with the alpha 1-antitrypsin deficiency allele Mmalton. J Biol Chem 1989;264:13938–45.CrossRefGoogle ScholarPubMed

Mahadeva, R, Chang, WS, Dafforn, TR, Oakley, DJ, Foreman, RC, Calvin, J, Wight, DG, et al. Heteropolymerization of S, I, and Z alpha1-antitrypsin and liver cirrhosis. J Clin Invest 1999;103:999–1006.CrossRefGoogle Scholar

Dafforn, TR, Mahadeva, R, Elliott, PR, Sivasothy, P, Lomas, DA. A kinetic mechanism for the polymerization of alpha1-antitrypsin. J Biol Chem 1999;274:9548–55.CrossRefGoogle ScholarPubMed

Yamasaki, M, Li, W, Johnson, DJ, Huntington, JA. Crystal structure of a stable dimer reveals the molecular basis of serpin polymerization. Nature 2008;455:1255–8.CrossRefGoogle ScholarPubMed

Whisstock, JC, Silverman, GA, Bird, PI, Bottomley, SP, Kaiserman, D, Luke, CJ, Pak, SC, et al. Serpins flex their muscle: II. Structural insights into target peptidase recognition, polymerization, and transport functions. J Biol Chem 2010;285:24307–12.Google ScholarPubMed

Yamasaki, M, Sendall, TJ, Pearce, MC, Whisstock, JC, Huntington, JA. Molecular basis of alpha1-antitrypsin deficiency revealed by the structure of a domain-swapped trimer. EMBO Rep 2011;12:1011–17.CrossRefGoogle ScholarPubMed

Huang, X, Zheng, Y, Zhang, F, Wei, Z, Wang, Y, Carrell, RW, Read, RJ, et al. Molecular mechanism of Z alpha1-antitrypsin deficiency. J Biol Chem 2016;291:15674–86.CrossRefGoogle ScholarPubMed

Lin, L, Schmidt, B, Teckman, J, Perlmutter, DH. A naturally occurring nonpolymerogenic mutant of alpha 1-antitrypsin characterized by prolonged retention in the endoplasmic reticulum. J Biol Chem 2001;276:33893–8.CrossRefGoogle ScholarPubMed

Schmidt, BZ, Perlmutter, DH. Grp78, Grp94, and Grp170 interact with alpha1-antitrypsin mutants that are retained in the endoplasmic reticulum. Am J Physiol Gastrointest Liver Physiol 2005;289:G444–55.CrossRefGoogle ScholarPubMed

Kuznetsov, G, Nigam, SK. Folding of secretory and membrane proteins. N Engl J Med 1998;339:1688–95.CrossRefGoogle ScholarPubMed

Davis, RL, Shrimpton, AE, Holohan, PD, Bradshaw, C, Feiglin, D, Collins, GH, Sonderegger, P, et al. Familial dementia caused by polymerization of mutant neuroserpin. Nature 1999;401:376–9.CrossRefGoogle ScholarPubMed

Perlmutter DH. Alpha-1-antitrypsin deficiency: importance of proteasomal and autophagic degradative pathways in disposal of liver disease-associated protein aggregates. Annu Rev Med 2011;62:333–45.Google Scholar

Wu, Y, Whitman, I, Molmenti, E, Moore, K, Hippenmeyer, P, Perlmutter, DH. A lag in intracellular degradation of mutant alpha 1-antitrypsin correlates with the liver disease phenotype in homozygous PiZZ alpha 1-antitrypsin deficiency. Proc Natl Acad Sci U S A 1994;91:9014–18.CrossRefGoogle ScholarPubMed

Kamimoto, T, Shoji, S, Hidvegi, T, Mizushima, N, Umebayashi, K, Perlmutter, DH, Yoshimori, T. Intracellular inclusions containing mutant alpha1-antitrypsin Z are propagated in the absence of autophagic activity. J Biol Chem 2006;281:4467–76.CrossRefGoogle Scholar

Kruse, KB, Brodsky, JL, McCracken, AA. Characterization of an ERAD gene as VPS30/ATG6 reveals two alternative and functionally distinct protein quality control pathways: one for soluble Z variant of human alpha-1 proteinase inhibitor (A1PiZ) and another for aggregates of A1PiZ. Mol Biol Cell 2006;17:203–12.CrossRefGoogle Scholar

Kruse, KB, Dear, A, Kaltenbrun, ER, Crum, BE, George, PM, Brennan, SO, McCracken, AA. Mutant fibrinogen cleared from the endoplasmic reticulum via endoplasmic reticulum-associated protein degradation and autophagy: an explanation for liver disease. Am J Pathol 2006;168:1299–308.CrossRefGoogle ScholarPubMed

Cabral, CM, Choudhury, P, Liu, Y, Sifers, RN. Processing by endoplasmic reticulum mannosidases partitions a secretion-impaired glycoprotein into distinct disposal pathways. J Biol Chem 2000;275:25015–22.CrossRefGoogle ScholarPubMed

Gelling, CL, Dawes, IW, Perlmutter, DH, Fisher, EA, Brodsky, JL. The endosomal protein-sorting receptor sortilin has a role in trafficking alpha-1 antitrypsin. Genetics 2012;192:889–903.CrossRefGoogle Scholar

Long, OS, Benson, JA, Kwak, JH, Luke, CJ, Gosai, SJ, O’Reilly, LP, Wang, Y, et al. A C. elegans model of human alpha1-antitrypsin deficiency links components of the RNAi pathway to misfolded protein turnover. Hum Mol Genet 2014;23:5109–22.CrossRefGoogle Scholar

Mizushima, N, Yamamoto, A, Matsui, M, Yoshimori, T, Ohsumi, Y. In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol Biol Cell 2004;15:1101–11.CrossRefGoogle ScholarPubMed

Hidvegi, T, Mirnics, K, Hale, P, Ewing, M, Beckett, C, Perlmutter, DH. Regulator of G signaling 16 is a marker for the distinct endoplasmic reticulum stress state associated with aggregated mutant alpha1-antitrypsin Z in the classical form of alpha1-antitrypsin deficiency. J Biol Chem 2007;282:27769–80.CrossRefGoogle Scholar

Hidvegi, T, Schmidt, BZ, Hale, P, Perlmutter, DH. Accumulation of mutant alpha1-antitrypsin Z in the endoplasmic reticulum activates caspases-4 and -12, NFkappaB, and BAP31 but not the unfolded protein response. J Biol Chem 2005;280:39002–15.CrossRefGoogle Scholar

Mukherjee, A, Hidvegi, T, Araya, P, Ewing, M, Stolz, DB, Perlmutter, DH. NFkappaB mitigates the pathological effects of misfolded alpha1-antitrypsin by activating autophagy and an integrated program of proteostasis mechanisms. Cell Death Differ 2019;26(3):455–69.CrossRefGoogle Scholar

Liao, Y, Shikapwashya, ON, Shteyer, E, Dieckgraefe, BK, Hruz, PW, Rudnick, DA. Delayed hepatocellular mitotic progression and impaired liver regeneration in early growth response-1-deficient mice. J Biol Chem 2004;279:43107–16.CrossRefGoogle ScholarPubMed

Teckman, JH, An, JK, Blomenkamp, K, Schmidt, B, Perlmutter, D. Mitochondrial autophagy and injury in the liver in alpha 1-antitrypsin deficiency. Am J Physiol Gastrointest Liver Physiol 2004;286:G851–62.CrossRefGoogle ScholarPubMed

Hidvegi, T, Stolz, DB, Alcorn, JF, Yousem, SA, Wang, J, Leme, AS, Houghton, AM, et al. Enhancing autophagy with drugs or lung-directed gene therapy reverses the pathological effects of respiratory epithelial cell proteinopathy. J Biol Chem 2015;290:29742–57.CrossRefGoogle ScholarPubMed

Pastore, N, Attanasio, S, Granese, B, Castello, R, Teckman, J, Wilson, AA, Ballabio, A, et al. Activation of the c-Jun N-terminal kinase pathway aggravates proteotoxicity of hepatic mutant Z alpha1-antitrypsin. Hepatology 2017;65:1865–74.CrossRefGoogle ScholarPubMed

Pan, S, Huang, L, McPherson, J, Muzny, D, Rouhani, F, Brantly, M, Gibbs, R, et al. Single nucleotide polymorphism-mediated translational suppression of endoplasmic reticulum mannosidase I modifies the onset of end-stage liver disease in alpha1-antitrypsin deficiency. Hepatology 2009;50:275–81.CrossRefGoogle ScholarPubMed

Pan, S, Wang, S, Utama, B, Huang, L, Blok, N, Estes, MK, Moremen, KW, et al. Golgi localization of ERManI defines spatial separation of the mammalian glycoprotein quality control system. Mol Biol Cell 2011;22:2810–22.CrossRefGoogle ScholarPubMed

Iannotti, MJ, Figard, L, Sokac, AM, Sifers, RN. A Golgi-localized mannosidase (MAN1B1) plays a non-enzymatic gatekeeper role in protein biosynthetic quality control. J Biol Chem 2014;289:11844–58.CrossRefGoogle Scholar

Chappell, S, Guetta-Baranes, T, Hadzic, N, Stockley, R, Kalsheker, N. Polymorphism in the endoplasmic reticulum mannosidase I (MAN1B1) gene is not associated with liver disease in individuals homozygous for the Z variant of the alpha1-antitrypsin protease inhibitor (PiZZ individuals). Hepatology 2009;50:1315, author reply 1315–16.CrossRefGoogle Scholar

Joly, P, Lachaux, A, Ruiz, M, Restier, L, Belmalih, A, Chapuis-Cellier, C, Francina, A, et al. SERPINA1 and MAN1B1 polymorphisms are not linked to severe liver disease in a French cohort of alpha-1 antitrypsin deficiency children. Liver Int 2017;37:1608–11.CrossRefGoogle ScholarPubMed

Chappell, S, Hadzic, N, Stockley, R, Guetta-Baranes, T, Morgan, K, Kalsheker, N. A polymorphism of the alpha1-antitrypsin gene represents a risk factor for liver disease. Hepatology 2008;47:127–32.Google ScholarPubMed

Hubner, RH, Leopold, PL, Kiuru, M, De, BP, Krause, A, Crystal, RG. Dysfunctional glycogen storage in a mouse model of alpha1-antitrypsin deficiency. Am J Respir Cell Mol Biol 2009;40:239–47.CrossRefGoogle Scholar

Piccolo, P, Annunziata, P, Soria, LR, Attanasio, S, Barbato, A, Castello, R, Carissimo, A, et al. Down-regulation of hepatocyte nuclear factor-4alpha and defective zonation in livers expressing mutant Z alpha1-antitrypsin. Hepatology 2017;66:124–35.CrossRefGoogle ScholarPubMed

Teckman, J, Perlmutter, DH. Conceptual advances in the pathogenesis and treatment of childhood metabolic liver disease.Gastroenterology 1995;108:1263–79.CrossRefGoogle ScholarPubMed

Tafaleng, EN, Chakraborty, S, Han, B, Hale, P, Wu, W, Soto-Gutierrez, A, Feghali-Bostwick, CA, et al. Induced pluripotent stem cells model personalized variations in liver disease resulting from alpha1-antitrypsin deficiency. Hepatology 2015;62:147–57.Google ScholarPubMed

Lindblad, D, Blomenkamp, K, Teckman, J. Alpha-1-antitrypsin mutant Z protein content in individual hepatocytes correlates with cell death in a mouse model. Hepatology 2007;46:1228–35.CrossRefGoogle Scholar

Dooley, S, Hamzavi, J, Ciuclan, L, Godoy, P, Ilkavets, I, Ehnert, S, Ueberham, E, et al. Hepatocyte-specific Smad7 expression attenuates TGF-beta-mediated fibrogenesis and protects against liver damage. Gastroenterology 2008;135:642–59.CrossRefGoogle ScholarPubMed

Bridges, JP, Wert, SE, Nogee, LM, Weaver, TE. Expression of a human surfactant protein C mutation associated with interstitial lung disease disrupts lung development in transgenic mice. J Biol Chem 2003;278:52739–46.CrossRefGoogle ScholarPubMed

Young, LR, Gulleman, PM, Bridges, JP, Weaver, TE, Deutsch, GH, Blackwell, TS, McCormack, FX. The alveolar epithelium determines susceptibility to lung fibrosis in Hermansky-Pudlak syndrome. Am J Respir Crit Care Med 2012;186:1014–24.CrossRefGoogle ScholarPubMed

Bhuiyan, MS, Pattison, JS, Osinska, H, James, J, Gulick, J, McLendon, PM, Hill, JA, et al. Enhanced autophagy ameliorates cardiac proteinopathy. J Clin Invest 2013;123:5284–97.CrossRefGoogle ScholarPubMed

Doppler, K, Mittelbronn, M, Lindner, A, Bornemann, A. Basement membrane remodelling and segmental fibrosis in sporadic inclusion body myositis. Neuromuscul Disord 2009;19:406–11.CrossRefGoogle ScholarPubMed

Nogalska, A, D’Agostino, C, Terracciano, C, Engel, WK, Askanas, V. Impaired autophagy in sporadic inclusion-body myositis and in endoplasmic reticulum stress-provoked cultured human muscle fibers. Am J Pathol 2010;177:1377–87.CrossRefGoogle ScholarPubMed

Rudnick, DA, Liao, Y, An, JK, Muglia, LJ, Perlmutter, DH, Teckman, JH. Analyses of hepatocellular proliferation in a mouse model of alpha-1-antitrypsin deficiency. Hepatology 2004;39:1048–55.CrossRefGoogle Scholar

Rudnick, DA, Perlmutter, DH. Alpha-1-antitrypsin deficiency: a new paradigm for hepatocellular carcinoma in genetic liver disease. Hepatology 2005;42:514–21.CrossRefGoogle ScholarPubMed

Ding, J, Yannam, GR, Roy-Chowdhury, N, Hidvegi, T, Basma, H, Rennard, SI, Wong, RJ, et al. Spontaneous hepatic repopulation in transgenic mice expressing mutant human alpha1-antitrypsin by wild-type donor hepatocytes. J Clin Invest 2011;121:1930–4.CrossRefGoogle ScholarPubMed

Kemmer, N, Kaiser, T, Zacharias, V, Neff, GW. Alpha-1-antitrypsin deficiency: outcomes after liver transplantation. Transplant Proc 2008;40:1492–4.CrossRefGoogle ScholarPubMed

Tannuri, AC, Gibelli, NE, Ricardi, LR, Santos, MM, Maksoud-Filho, JG, Pinho-Apezzato, ML, Silva, MM, et al. Living related donor liver transplantation in children. Transplant Proc 2011;43:161–4.CrossRefGoogle ScholarPubMed

Sarkar, S, Perlstein, EO, Imarisio, S, Pineau, S, Cordenier, A, Maglathlin, RL, Webster, JA, et al. Small molecules enhance autophagy and reduce toxicity in Huntington’s disease models. Nat Chem Biol 2007;3:331–8.CrossRefGoogle ScholarPubMed

Li, C, Xiao, P, Gray, SJ, Weinberg, MS, Samulski, RJ. Combination therapy utilizing shRNA knockdown and an optimized resistant transgene for rescue of diseases caused by misfolded proteins. Proc Natl Acad Sci U S A 2011;108:14258–63.CrossRefGoogle Scholar

Mueller, C, Tang, Q, Gruntman, A, Blomenkamp, K, Teckman, J, Song, L, Zamore, PD, et al. Sustained miRNA-mediated knockdown of mutant AAT with simultaneous augmentation of wild-type AAT has minimal effect on global liver miRNA profiles. Mol Ther 2012;20:590–600.CrossRefGoogle ScholarPubMed

Guo, S, Booten, SL, Aghajan, M, Hung, G, Zhao, C, Blomenkamp, K, Gattis, D, et al. Antisense oligonucleotide treatment ameliorates alpha-1 antitrypsin-related liver disease in mice. J Clin Invest 2014;124:251–61.CrossRefGoogle ScholarPubMed

Pastore, N, Blomenkamp, K, Annunziata, F, Piccolo, P, Mithbaokar, P, Maria Sepe, R, Vetrini, F, et al. Gene transfer of master autophagy regulator TFEB results in clearance of toxic protein and correction of hepatic disease in alpha-1-anti-trypsin deficiency. EMBO Mol Med 2013;5:397–412.CrossRefGoogle ScholarPubMed

Shen, S, Sanchez, ME, Blomenkamp, K, Corcoran, EM, Marco, E, Yudkoff, CJ, Jiang, H, et al. Amelioration of alpha-1 antitrypsin deficiency diseases with genome editing in transgenic mice. Hum Gene Ther 2018;29(8):861–73.CrossRefGoogle ScholarPubMed

Song, CQ, Wang, D, Jiang, T, O’Connor, K, Tang, Q, Cai, L, Li, X, et al. In vivo genome editing partially restores alpha1-antitrypsin in a murine model of AAT deficiency. Hum Gene Ther 2018;29(8):853–60.CrossRefGoogle Scholar

Mallya, M, Phillips, RL, Saldanha, SA, Gooptu, B, Brown, SC, Termine, DJ, Shirvani, AM, et al. Small molecules block the polymerization of Z alpha1-antitrypsin and increase the clearance of intracellular aggregates. J Med Chem 2007;50:5357–63.CrossRefGoogle Scholar

Alam, S, Wang, J, Janciauskiene, S, Mahadeva, R. Preventing and reversing the cellular consequences of Z alpha-1 antitrypsin accumulation by targeting s4A. J Hepatol 2012;57:116–24.CrossRefGoogle Scholar

Burrows, JA, Willis, LK, Perlmutter, DH. Chemical chaperones mediate increased secretion of mutant alpha 1-antitrypsin (alpha 1-AT) Z: a potential pharmacological strategy for prevention of liver injury and emphysema in alpha 1-AT deficiency. Proc Natl Acad Sci U S A 2000;97:1796–801.CrossRefGoogle Scholar

Teckman, JH. Lack of effect of oral 4-phenylbutyrate on serum alpha-1-antitrypsin in patients with alpha-1-antitrypsin deficiency: a preliminary study. J Pediatr Gastroenterol Nutr 2004;39:34–7.CrossRefGoogle ScholarPubMed

Bouchecareilh, M, Hutt, DM, Szajner, P, Flotte, TR, Balch, WE. Histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA)-mediated correction of alpha1-antitrypsin deficiency. J Biol Chem 2012;287:38265–78.CrossRefGoogle ScholarPubMed

Fox, IJ, Chowdhury, JR, Kaufman, SS, Goertzen, TC, Chowdhury, NR, Warkentin, PI, Dorko, K, et al. Treatment of the Crigler-Najjar syndrome type I with hepatocyte transplantation. N Engl J Med 1998;338:1422–6.CrossRefGoogle ScholarPubMed

Yusa, K, Rashid, ST, Strick-Marchand, H, Varela, I, Liu, PQ, Paschon, DE, Miranda, E, et al. Targeted gene correction of alpha1-antitrypsin deficiency in induced pluripotent stem cells. Nature 2011;478:391–4.CrossRefGoogle ScholarPubMed

Kosorok, MR, Wei, WH, Farrell, PM. The incidence of cystic fibrosis. Stat Med 1996;15:449–62.3.0.CO;2-X>CrossRefGoogle ScholarPubMed

Dodge, JA, Morison, S, Lewis, PA, et al. Incidence, population, and survival of cystic fibrosis in the UK, 1968–95. UK Cystic Fibrosis Survey Management Committee. Arch Dis Child 1997;77:493–6.Google Scholar

Anderson, D. Cystic fibrosis of the pancreas and its relation to celiac disease: a clinical and pathological study. Am J Dis Child 1938;56(2):344–99.Google Scholar

Quinton, PM. Chloride impermeability in cystic fibrosis. Nature 1983;301 (5899):421–2.CrossRefGoogle ScholarPubMed

Riordan, JR, Rommens, JM, Kerem, B, et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 1989;245 (4922):1066–73.CrossRefGoogle ScholarPubMed

Schwiebert, EM, Benos, DJ, Egan, ME, Stutts, MJ, Guggino, WB. CFTR is a conductance regulator as well as a chloride channel. Physiol Rev 1999;79(1 Suppl):S145–S166.CrossRefGoogle ScholarPubMed

Gabriel, SE, Clarke, LL, Boucher, RC, Stutts, MJ. CFT R and outward rectifying chloride channels are distinct proteins with a regulatory relationship. Nature 1993;363(6426):263–8.CrossRefGoogle Scholar

Dutta, AK, Khimji, AK, Kresge, C, et al. Identification and functional characterization of TMEM16A, a Ca²⁺-activated Cl^– channel activated by extracellular nucleotides in biliary epithelium. J Biol Chem 2011;286: 766–76.CrossRefGoogle ScholarPubMed

Li, Q, Kresge, C, Bugde, A, Lamphere, M, Park, JY, Feranchak, AP. Regulation of mechanosensitive biliary epithelial transport by the epithelial Na(+) channel. Hepatology 2016;63(2):538–49. doi:10.1002/hep.28301CrossRefGoogle ScholarPubMed

Braunstein, GM, Roman, RM, Clancy, JP, et al. Cystic fibrosis transmembrane conductance regulator facilitates ATP release by stimulating a separate ATP release channel for autocrine control of cell volume regulation. J Biol Chem 2001;276:6621–30.CrossRefGoogle ScholarPubMed

Fouassier, L, Duan, CY, Feranchak, AP, et al. Ezrin-radixin-moesin-binding phosphoprotein 50 is expressed at the apical membrane of rat liver epithelia. Hepatology 2001;33:166–76.CrossRefGoogle ScholarPubMed

Cohn, JA, Strong, TV, Picciotto, MR, et al. Localization of the cystic fibrosis transmembrane conductance regulator in human bile duct epithelial cells. Gastroenterology 1993;105:1857–64.CrossRefGoogle ScholarPubMed

Fitz, JG, Basavappa, S, McGill, J, Melhus, O, Cohn, JA. Regulation of membrane chloride currents in rat bile duct epithelial cells. J Clin Invest 1993;91:319–28.CrossRefGoogle ScholarPubMed

Fitz, JG. (1996). Cellular mechanisms of bile secretion. In Zakim, D, Boyer, TD (Eds.), Hepatology, 3rd edn (pp. 362–76). Philadelphia, PA: Saunders.Google Scholar

Dutta, AK, Khimji, AK, Sathe, M, et al. Identification and functional characterization of the intermediate-conductance Ca(²⁺)-activated K(+) channel (IK-1) in biliary epithelium. Am J Physiol Gastrointest Liver Physiol 2009;297:G1009–G1018.CrossRefGoogle Scholar

Feranchak, AP, Sokol, RJ. Cholangiocyte biology and cystic fibrosis liver disease. Sem Liv Disease 2001;21:471–88.Google ScholarPubMed

Clarke, LL, Grubb, BR, Yankaskas, JR, et al. Relationship of a non-cystic fibrosis transmembrane conductance regulator-mediated chloride conductance to organ-level disease in Cftr(–/–) mice. Proc Natl Acad Sci USA 1994;91:479–83.CrossRefGoogle ScholarPubMed

Dutta, AK, Khimji, AK, Kresge, C, Bugde, A, Dougherty, M, Esser, V, Ueno, Y, Glaser, SS, Alpini, G, Rockey, DC, Feranchak, AP. Identification and functional characterization of TMEM16A, a Ca²⁺-activated Cl^– channel activated by extracellular nucleotides, in biliary epithelium. J Biol Chem. 2011 Jan 7;286(1):766–76. doi: 10.1074/jbc.M110.164970. Epub 2010 Nov 1. https://pubmed.ncbi.nlm.nih.gov/21041307/CrossRefGoogle Scholar

Feranchak, AP, Fitz, JG. Adenosine triphosphate release and purinergic regulation of cholangiocyte transport. Semin Liver Dis 2002;22:251–62.CrossRefGoogle ScholarPubMed

Dutta, AK, Woo, K, Doctor, RB, Fitz, JG, Feranchak, AP. Extracellular nucleotides stimulate Cl^– currents in biliary epithelia through receptor-mediated IP3 and Ca²⁺ release. Am J Physiol Gastrointest Liver Physiol 2008;295:G1004–G1015.CrossRefGoogle ScholarPubMed

Woo, K, Dutta, AK, Patel, V, Kresge, C, Feranchak, AP. Fluid flow induces mechanosensitive ATP release, calcium signalling and Cl^– transport in biliary epithelial cells through a PKCzeta-dependent pathway. J Physiol 2008;586(Pt 11):2779–98.CrossRefGoogle ScholarPubMed

Fiorotto, R, Scirpo, R, Trauner, M, et al. Loss of CFTR affects biliary epithelium innate immunity and causes TLR4–NF-κB: mediated inflammatory response in mice. Gastroenterology 2011;141(4):1498–508.e5. doi:10.1053/j.gastro.2011.06.052CrossRefGoogle ScholarPubMed

Fiorotto, R, Villani, A, Kourtidis, A, et al. The cystic fibrosis transmembrane conductance regulator controls biliary epithelial inflammation and permeability by regulating Src tyrosine kinase activity. Hepatology 2016;64(6):2118–34. doi:10.1002/hep.28817CrossRefGoogle ScholarPubMed

Gabriel, SE, Brigman, KN, Koller, BH, Boucher, RC, Stutts, MJ. Cystic fibrosis heterozygote resistance to cholera toxin in the cystic fibrosis mouse model. Science 1994;266(5182):107–9.CrossRefGoogle ScholarPubMed

Quinton, PM. Role of epithelial HCO3 transport in mucin secretion: lessons from cystic fibrosis. Am J Physiol Cell Physiol 2010;299:C1222–C1233.CrossRefGoogle ScholarPubMed

Debray, D, El Mourabit, H, Merabtene, F, et al. Diet-induced dysbiosis and genetic background synergize with cystic fibrosis transmembrane conductance regulator deficiency to promote cholangiopathy in mice. Hepatol Commun 2018;2(12):1533–49. doi:10.1002/hep4.1266CrossRefGoogle ScholarPubMed

Scanlan, PD, Buckling, A, Kong, W, Wild, Y, Lynch, S V, Harrison, F. Gut dysbiosis in cystic fibrosis. J Cyst Fibros 2012;11(5):454–5. doi:10.1016/j.jcf.2012.03.007CrossRefGoogle ScholarPubMed

Parisi, GF, Papale, M, Rotolo, N, et al. Severe disease in cystic fibrosis and fecal calprotectin levels. Immunobiology 2017;222(3):582–6. doi:10.1016/j.imbio.2016.11.005CrossRefGoogle ScholarPubMed

Blanco, PG, Zaman, MM, Junaidi, O, et al. Induction of colitis in cftr −/− mice results in bile duct injury. Am J Physiol Liver Physiol. 2004;287(2):G491–G496. doi:10.1152/ajpgi.00452.2003Google ScholarPubMed

Flass, T, Tong, S, Frank, DN, et al. Intestinal lesions are associated with altered intestinal microbiome and are more frequent in children and young adults with cystic fibrosis and cirrhosis. PLoS One. 2015;10(2):e0116967. doi:10.1371/journal.pone.0116967CrossRefGoogle Scholar

Smith, JL, Lewindon, PJ, Hoskins, AC, et al. Endogenous ursodeoxycholic acid and cholic acid in liver disease due to cystic fibrosis. Hepatology 2004;39:1673–82.CrossRefGoogle ScholarPubMed

Brazova, J, Sediva, A, Pospisilova, D, et al. Differential cytokine profile in children with cystic fibrosis. Clin Immunol. 2005;115(2):210–15. doi:10.1016/j.clim.2005.01.013CrossRefGoogle ScholarPubMed

Jacquot, J, Tabary, O, Le Rouzic, P, Clement, A. Airway epithelial cell inflammatory signalling in cystic fibrosis. Int J Biochem Cell Biol. 2008;40(9):1703–15. doi:10.1016/j.biocel.2008.02.002CrossRefGoogle ScholarPubMed

Paats, MS, Bergen, IM, Bakker, M, et al. Cytokines in nasal lavages and plasma and their correlation with clinical parameters in cystic fibrosis. J Cyst Fibros. 2013;12(6):623–9. doi:10.1016/j.jcf.2013.05.002CrossRefGoogle ScholarPubMed

McGill, JM, Yen, MS, Cummings, OW, et al. Interleukin-5 inhibition of biliary cell chloride currents and bile flow. Am J Physiol Gastrointest Liver Physiol 2001;280(4):G738–45. doi:10.1152/ajpgi.2001.280.4.G738CrossRefGoogle ScholarPubMed

Spirlì, C, Fabris, L, Duner, E, et al. Cytokine-stimulated nitric oxide production inhibits adenylyl cyclase and cAMP-dependent secretion in cholangiocytes. Gastroenterology 2003;124(3):737–53. doi:10.1053/gast.2003.50100CrossRefGoogle ScholarPubMed

Spirlì, C, Nathanson, MH, Fiorotto, R, et al. Proinflammatory cytokines inhibit secretion in rat bile duct epithelium. Gastroenterology 2001;121(1):156–69. doi:10.1053/gast.2001.25516CrossRefGoogle ScholarPubMed

Sun, H, Harris, WT, Kortyka, S, et al. Tgf-beta downregulation of distinct chloride channels in cystic fibrosis-affected epithelia. PLoS One. 2014;9(9):e106842. doi:10.1371/journal.pone.0106842CrossRefGoogle ScholarPubMed

Lewindon, PJ, Pereira, TN, Hoskins, AC, et al. The role of hepatic stellate cells and transforming growth factor-beta(1) in cystic fibrosis liver disease. Am J Pathol 2002;160:1705–15.CrossRefGoogle Scholar

Fiorotto, R, Amenduni, M, Mariotti, V, et al. Animal models for cystic fibrosis liver disease. Biochim Biophys Acta – Mol Basis Dis 2019;1865(5):965–9. doi:10.1016/j.bbadis.2018.07.026CrossRefGoogle ScholarPubMed

Bartlett, JR, Friedman, KJ, Ling, SC, et al. Genetic modifiers of liver disease in cystic fibrosis. JAMA 2009;302:1076–83.CrossRefGoogle ScholarPubMed

Duthie, A, Doherty, DG, Donaldson, PT, et al. The major histocompatibility complex influences the development of chronic liver disease in male children and young adults with cystic fibrosis. J Hepatol 1995;23:532–7.CrossRefGoogle Scholar

Cystic Fibrosis Foundation (CFF). 2017 Patient Registry: Annual Data Report. Cyst Fibros Found Patient Regist. 2017:92.Google Scholar

Vawter, GF, Shwachman, H. Cystic fibrosis in adults: an autopsy study. Pathol Annu 1979;14:357–82.Google Scholar

Debray, D, Kelly, D, Houwen, R, Strandvik, B, Colombo, C. Best practice guidance for the diagnosis and management of cystic fibrosis-associated liver disease. J Cyst Fibros 2011;10:S29–S36.CrossRefGoogle ScholarPubMed

Boëlle, P, Debray, D, Guillot, L, et al. Cystic fibrosis liver disease: outcomes and risk factors in a large cohort of French patients. Hepatology 2019;69(4):1648–56. doi:http://dx.doi.org/10.1002/hep.30148CrossRefGoogle Scholar

Koh, C, Sakiani, S, Surana, P, et al. Adult-onset cystic fibrosis liver disease: diagnosis and characterization of an underappreciated entity. Hepatology 2017;66(2):591–601. doi:https://dx.doi.org/10.1002/hep.29217CrossRefGoogle ScholarPubMed

Colombo, C, Apostolo, MG, Ferrari, M, et al. Analysis of risk factors for the development of liver disease associated with cystic fibrosis. J Pediatr 1994;124:393–9.CrossRefGoogle ScholarPubMed

Sokol, RJ, Durie, PR. Recommendations for management of liver and biliary tract disease in cystic fibrosis. Cystic Fibrosis Foundation Hepatobiliary Disease Consensus Group. J Pediatr Gastroenterol Nutr 1999;28(Suppl1):S1–S13.Google ScholarPubMed

Flass, T, Narkewicz, MR. Cirrhosis and other liver disease in cystic fibrosis. J Cyst Fibros. 2013;12(2):116–24. doi:https://dx.doi.org/10.1016/j.jcf.2012.11.010CrossRefGoogle ScholarPubMed

Sokol, RJ, Carroll, NM, Narkewicz, MR, et al. Liver blood tests during the first decade of life in children with cystic fibrosis identified by newborn screening. Pediatr Pulm 1994;10:275.Google Scholar

Woodruff, SA, Sontag, MK, Accurso, FJ, Sokol, RJ, Narkewicz, MR. Prevalence of elevated liver enzymes in children with cystic fibrosis diagnosed by newborn screen. J Cyst Fibros 2017;16(1):139–45. doi:https://dx.doi.org/10.1016/j.jcf.2016.08.002CrossRefGoogle ScholarPubMed

Loverdos, I, Gonska, T, Ling, SC. Platelet count enables early diagnosis of cystic fibrosis liver disease (Conference Workshop WS17.3). J Cyst Fibros. 2016;15:S28.CrossRefGoogle Scholar

Patriquin, H, Lenaerts, C, Smith, L, et al. Liver disease in children with cystic fibrosis: US-biochemical comparison in 195 patients. Radiology 1999;211: 229–32.CrossRefGoogle ScholarPubMed

Lenaerts, C, Lapierre, C, Patriquin, H, et al. Surveillance for cystic fibrosis- associated hepatobiliary disease: early ultrasound changes and predisposing factors. J Pediatr 2003;143:343–50.CrossRefGoogle ScholarPubMed

Narkewicz, MR. Cystic fibrosis liver disease: what is it and what happens as a result. Pediatr Pulmonol 2018;53(Supplement2):81–2. doi:http://dx.doi.org/10.1002/ppul.24151Google Scholar

Ling, SC, Ye, W, Leung, DH, et al. Liver ultrasound patterns in children with cystic fibrosis correlate with non-invasive tests of liver disease. J Pediatr Gastroenterol Nutr 2019;69:351. doi:10.1097/mpg.0000000000002413CrossRefGoogle Scholar

Ling, SC. The use of serum biomarkers and imaging in the diagnosis and prediction of outcomes in CF liver disease. Pediatr Pulmonol 2018;53(Supplement2):85–86. doi:http://dx.doi.org/10.1002/ppul.24151Google Scholar

Sathe, MN, Freeman, AJ. Gastrointestinal, pancreatic, and hepatobiliary manifestations of cystic fibrosis. Pediatr Clin North Am 2016;63(4):679–98. doi:https://dx.doi.org/10.1016/j.pcl.2016.04.008CrossRefGoogle ScholarPubMed

Aqul, A, Jonas, MM, Harney, S, et al. Correlation of transient elastography with severity of cystic fibrosis-related liver disease. J Pediatr Gastroenterol Nutr 2017;64(4):505–11. doi:https://dx.doi.org/10.1097/MPG.0000000000001448CrossRefGoogle ScholarPubMed

Gominon, A-L, Frison, E, Hiriart, J-B, et al. Assessment of liver disease progression in cystic fibrosis using transient elastography. J Pediatr Gastroenterol Nutr 2018;66(3):455–60. doi:https://dx.doi.org/10.1097/MPG.0000000000001822CrossRefGoogle ScholarPubMed

Lewindon, PJ, Puertolas-Lopez, MV. , Ramm, LE, et al. Accuracy of transient elastography data combined with APRI in detection and staging of liver disease in pediatric patients with cystic fibrosis. Clin Gastroenterol Hepatol 2019. doi:10.1016/j.cgh.2019.03.015CrossRefGoogle Scholar

Leung, DH, Khan, M, Minard, CG, et al. Aspartate aminotransferase to platelet ratio and fibrosis-4 as biomarkers in biopsy-validated pediatric cystic fibrosis liver disease. Hepatology 2015;62(5):1576–83. doi:https://dx.doi.org/10.1002/hep.28016CrossRefGoogle ScholarPubMed

Ling, SC, Ye, W, Leung, DH, et al. Baseline liver echotexture in children with cystic fibrosis predicts changes over time in non-invasive biomarkers of fibrosis and portal hypertension. J Pediatr Gastroenterol Nutr 2017;65(Supplement 1):77A-78A. doi:http://dx.doi.org/10.1097/MPG.0000000000001805Google Scholar

Cook, NL, Pereira, TN, Lewindon, PJ, Shepherd, RW, Ramm, GA. Circulating microRNAs as noninvasive diagnostic biomarkers of liver disease in children with cystic fibrosis. J Pediatr Gastroenterol Nutr 2015;60(2):247–54. doi:10.1097/MPG.0000000000000600CrossRefGoogle ScholarPubMed

Heuman, DM. Hepatoprotective properties of ursodeoxycholic acid. Gastroenterology 1993;104:1865–70.CrossRefGoogle ScholarPubMed

Shimokura, GH, McGill, JM, Schlenker, T, Fitz, JG. Ursodeoxycholate increases cytosolic calcium concentration and activates Cl^– currents in a biliary cell line. Gastroenterology 1995;109:965–72.CrossRefGoogle Scholar

Colombo, C, Crosignani, A, Assaisso, M, et al. Ursodeoxycholic acid therapy in cystic fibrosis-associated liver disease: a dose-response study. Hepatology 1992;16:924–30.CrossRefGoogle ScholarPubMed

Lindblad, A, Glaumann, H, Strandvik, B. A two-year prospective study of the effect of ursodeoxycholic acid on urinary bile acid excretion and liver morphology in cystic fibrosis-associated liver disease. Hepatology 1998;27:166–74.CrossRefGoogle ScholarPubMed

Nousia-Arvanitakis, S, Fotoulaki, M, Economou, H, Xefteri, M, Galli-Tsinopoulou, A. Long-term prospective study of the effect of ursodeoxycholic acid on cystic fibrosis-related liver disease. J Clin Gastroenterol 2001;32:324–8.CrossRefGoogle ScholarPubMed

Lindor, KD, Kowdley, KV, Luketic, VA, et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology 2009;50:808–14.CrossRefGoogle ScholarPubMed

Gong, Y, Huang, ZB, Christensen, E, Gluud, C. Ursodeoxycholic acid for primary biliary cirrhosis. Cochrane Database Syst Rev 2008;8:CD000551.Google Scholar

Ooi, CY, Nightingale, S, Durie, PR, Freedman, SD. Ursodeoxycholic acid in cystic fibrosis-associated liver disease. J Cyst Fibros 2012;11:72–3.CrossRefGoogle ScholarPubMed

Cheng, K, Ashby, D, Smyth, RL. Ursodeoxycholic acid for cystic fibrosis-related liver disease. Cochrane Database Syst Rev 2017;9:CD000222. doi:https://dx.doi.org/10.1002/14651858.CD000222.pub4Google ScholarPubMed

Ye, W, Narkewicz, MR, Leung, DH, et al. Variceal hemorrhage and adverse liver outcomes in patients with cystic fibrosis cirrhosis. J Pediatr Gastroenterol Nutr 2018;66(1):122–7. doi:https://dx.doi.org/10.1097/MPG.0000000000001728CrossRefGoogle ScholarPubMed

Lemoine, C, Lokar, J, McColley, SA, Alonso, EM, Superina, R. Cystic fibrosis and portal hypertension: Distal splenorenal shunt can prevent the need for future liver transplant. J Pediatr Surg 2019. doi:http://dx.doi.org/10.1016/j.jpedsurg.2019.01.035CrossRefGoogle Scholar

Molleston, J. Medical and surgical management of complication of portal hypertension in CF. Pediatr Pulmonol 2018;53:S84–5.Google Scholar

Gridelli, B. Liver: benefit of liver transplantation in patients with cystic fibrosis. Nat Rev Gastroenterol Hepatol 2011;8:187–8.CrossRefGoogle ScholarPubMed

Yang, Y, Raper, SE, Cohn, JA, Engelhardt, JF, Wilson, JM. An approach for treating the hepatobiliary disease of cystic fibrosis by somatic gene transfer. Proc Natl Acad Sci USA 1993;90:4601–5.CrossRefGoogle ScholarPubMed

Becq, F, Mall, MA, Sheppard, DN, Conese, M, Zegarra-Moran, O. Pharmacological therapy for cystic fibrosis: from bench to bedside.J Cyst Fibros 2011;10(Suppl2):S129–S145.CrossRefGoogle ScholarPubMed

Hayes, D, Warren, PS, McCoy, KS, Sheikh, SI. Improvement of hepatic steatosis in cystic fibrosis with ivacaftor therapy. J Pediatr Gastroenterol Nutr 2015;60(5):578–9. doi:10.1097/MPG.0000000000000765CrossRefGoogle ScholarPubMed

Chaudary, N. Triplet CFTR modulators: future prospects for treatment of cystic fibrosis. Ther Clin Risk Manag 2018;14:2375–83. doi:10.2147/TCRM.S147164CrossRefGoogle ScholarPubMed

Bodewes, FAJA, van der Wulp, MYM, Beharry, S, et al. Altered intestinal bile salt biotransformation in a cystic fibrosis (Cftr−/−) mouse model with hepato-biliary pathology. J Cyst Fibros 2015;14(4):440–6. doi:10.1016/j.jcf.2014.12.010CrossRefGoogle Scholar

Van de Peppel, IP, Bodewes, FAJA, Verkade, HJ, Jonker, JW. Bile acid homeostasis in gastrointestinal and metabolic complications of cystic fibrosis. J Cyst Fibros. 2019;18(3):313–20. doi:10.1016/j.jcf.2018.08.009CrossRefGoogle ScholarPubMed

Wiest, R, Albillos, A, Trauner, M, Bajaj, JS, Jalan, R. Targeting the gut-liver axis in liver disease. J Hepatol 2017;67(5):1084–103. doi:10.1016/j.jhep.2017.05.007CrossRefGoogle ScholarPubMed

Mason, HH, Turner, ME. Chronic galactosemia. Am J Dis Child 1935;50:359.CrossRefGoogle Scholar

Wada, Y, Kikuchi, A, Arai-Ichinoi, N, Sakamoto, O, Takezawa, Y, Iwasawa, S, Niihori, T Nyuzuki, H. U. A.: biallelic GALM pathogenic variants cause a novel type of galactosemia. Genet Med 2019;6:1286–94.Google Scholar

Donnell, GN, Bergren, WR, Cleland, RS. Galactosemia. Pediatr Clin North Am 1960;7:315–32.CrossRefGoogle ScholarPubMed

Gitzelmann, R. Hereditary galactokinase deficiency, a newly recognized cause of juvenile cataracts. Pediatr Res 1967;1:14–23.CrossRefGoogle Scholar

Gitzelmann, R, Steinmann, B, Mitchell, B, et al. Uridine diphosphate galactose-4- epimerase deficiency. IV. Report of eight cases in three families. Helv Paediatr Acta 1977;31:441–52.Google ScholarPubMed

Holton, JB, Gillett, MG, MacFaul, R, et al. Galactosemia: a new severe variant due to uridine diphosphate galactose-4-epimerase deficiency.Arch Dis Child 1981;56: 885–7.CrossRefGoogle ScholarPubMed

Holton, JB. Galactosaemia: pathogenesis and treatment. J Inherit Metab Dis 1996;19:3–7.CrossRefGoogle ScholarPubMed

Hopfer, U. (1987). Membrane transport mechanisms for hexoses and amino acids in the small intestine. In Johnson, LR, Christensen, J, Jackson, MJ (Eds.) Physiology of the Gastrointestinal Tract, 2nd edn. (pp. 1499–526). New York: Raven Press.Google Scholar

Timson, DJ. Type IV galactosemia. Genet Med 2019;21(6):1283–5.CrossRefGoogle ScholarPubMed

Shin-Buehring, YS, Beier, T, Tan, A, et al. Galactokinase and galactose-1-phosphate uridyltransferase (transferase) and galactokinase in human fetal organs. Pediatr Res 1977;11:1012.CrossRefGoogle ScholarPubMed

Coelho, AI, Rubio-Gozalbo, ME, Vicente, JB, Rivera, I. Sweet and sour: an update on classic galactosemia. J Inherit Metab Dis 2017;40(3):325–42.CrossRefGoogle ScholarPubMed

Segal, S, Blair, A. Some observations on the metabolism of d-galactose in normal man. J Clin Invest 1961;40:2016–25.CrossRefGoogle Scholar

Tygstrup, N. Determination of the hepatic elimination capacity (LM) of galactose by single injection. ScandJ Clin Lab Invest 1966;92(Suppl. 18):118–25.Google Scholar

Lemaire, HG, Muller-Hill, B. Nucleotide sequences of the gal E gene and the gal T gene of E. coli. Nucleic Acids Res 1986;14:7705–11.CrossRefGoogle Scholar

Flach, JE, Reichardt, TKV, Elsas, LJ. Sequence of a cDNA encoding human galactose-1-phosphate uridyl transferase. Mol Biol Med 1990;7:365–9.Google ScholarPubMed

Field, TL, Reznikoff, WS, Frey, PA. Galactose-1-phosphate uridylyltransferase: identification of histidine-164 and histidine-166 as critical residues by site-directed mutagenesis. Biochemistry 1989;28:2094–9.CrossRefGoogle ScholarPubMed

Reichardt, JKV, Woo, SLC. Molecular basis of galactosemia: mutations and polymorphisms in the gene encoding human galactose-1-phosphate uridyl transferase. Proc Natl Acad Sci USA 1991;88:2633–7.CrossRefGoogle Scholar

Calderon, FR, Pharsalker, AR, Crockett, DK, et al. Mutation database for the galactose-1-phosphate uridyltransferase (GALT) gene. Hum Mutat 2007;28:939–43.CrossRefGoogle ScholarPubMed

Tyfield, L, Reichardt, J, Fridovich-Keil, J, et al. Classical galactosemia and mutations at the galactose-1-phosphate uridyl transferase (GALT) gene. Hum Mutat 1999;13:417–30.3.0.CO;2-0>CrossRefGoogle ScholarPubMed

Reichardt, JK, Levy, HL, Woo, SL. Molecular characterization of two galactosemia mutations and one polymorphism: implications for structure–function analysis of human galactose-1-phosphate uridyltransferase. Biochemistry 1992;31:5430–3.CrossRefGoogle ScholarPubMed

Berry, GT. (1993). Classic galactosemia and clinical variant galactosemia. In Adam, MP, Ardinger, HH, Pagon, RA, Wallace, SE, Bean, LJ, Stephens, K, Amemiya, A. GeneReviews®. Seattle: University of Washington.Google Scholar

Wang, BB, Xu, YK, Ng, WG, et al. Molecular and biochemical basis of galactosemia. Mol Genet Metab 1998;63:263–9.CrossRefGoogle ScholarPubMed

Welling, L, Bernstein, LE, Berry, GT, Burlina, AB, Eyskens, F, Gautschi, M, Grünewald, S, Gubbels, CS. International clinical guideline for the management of classical galactosemia: diagnosis, treatment, and follow-up. J Inherit Metab Dis 2017;40(2):171–6.CrossRefGoogle Scholar

Levy, HL, Sepe, SJ, Shih, VE, et al. Sepsis due to Escherichia coli in neonates with galactosemia. N Engl J Med 1977;297:823–5.CrossRefGoogle ScholarPubMed

Litchfield, WJ, Wells, WW. Effects of galactose on free radical reactions of polymorphonuclear leukocytes. Arch Biochem Biophys 1978;188:26–30.CrossRefGoogle ScholarPubMed

Segal, S, Blair, A, Roth, H. The metabolism of galactose by patients with congenital galactosemia. Am J Med 1965;38:62–70.CrossRefGoogle Scholar

Segal, S. (1989). Disorders of galactose metabolism. In Stanbury, JB, Wyngaarden, JB, Frederickson, DS (Eds.) The Metabolic Basis of Inherited Disease, 6th edn. (pp. 453–80). New York: McGraw- Hill.Google Scholar

Belman, AL, Moshe, SL, Zimmerman, RD. Computered tomographic demonstration of cerebral edema in a child with galactosemia. Pediatrics 1986;78:606–9.Google Scholar

Sidbury, JB Jr. (1960). The role of galactose-1-phosphate in the pathogenesis of galactosemia. In Gardner, LE (Ed.), Molecular Genetics and Human Disease (p. 61). Springfield, IL: Charles C Thomas.Google Scholar

Tada, K. Glycogenesis and glycolysis in the liver from congenital galactosemia. Tohoku J Exp Med 1964;82:168–71.CrossRefGoogle ScholarPubMed

Keppler, D, Decker, K. Studies on the mechanisms of galactosamine hepatitis: accumulation of galactosamine-1-phosphate and its inhibition of UDP-glucose pyrophosphorylase. EurJ Biochem 1969;10:219–25.CrossRefGoogle Scholar

Quan-Ma, R, Wells, W. The distribution of galactitol in tissues of rats fed galactose. Biochem Biophys Res Commun 1965;20:486–90.CrossRefGoogle ScholarPubMed

Schwarz, V. The value of galactose phosphate determinations in the treatment of galactosemia. Arch Dis Child 1960;35:428–32.CrossRefGoogle Scholar

Thier, S, Fox, M, Rosenberg, L, et al. Hexose inhibition of amino acid uptake in the rat kidney cortex slice. Biochim Biophys Acta 1964;93:106–15.Google ScholarPubMed

Saunders, S, Isselbacher, KJ. Inhibition of intestinal amino acid transport by hexoses. Biochim Biophys Acta 1965;102:397–409.CrossRefGoogle ScholarPubMed

van Heyningen, R. Formation of polyols by the lens of the rat with “sugar” cataract. Nature 1959;184:194–5.CrossRefGoogle Scholar

Kinoshita, JH, Dvornik, D, Krami, M, et al. The effect of aldose reductase inhibitor on the galactose-exposed rabbit lens. Biochim Biophys Acta 1968;158:472–5.Google ScholarPubMed

Dische, Z, Zelmenis, G, Youlous, J. Studies on protein and protein synthesis during the development of galactose cataract. Am J Ophthalmol 1957;44:332–40.CrossRefGoogle Scholar

Kinoshita, JH, Merola, LO, Tung, B. Changes in cation permeability in the galactose-exposed rabbit lens. Exp Eye Res 1968;7:80–90.CrossRefGoogle ScholarPubMed

Granett, SE, Kozak, LP, McIntyre, JP, et al. Studies on cerebral energy metabolism during the course of galactose neurotoxicity in chicks.J Neurochem 1972;19:1659–70.CrossRefGoogle ScholarPubMed

Malone, JI, Wells, HJ, Segal, S. Galactose toxicity in the chick: hyperosmolality. Science 1971;174:952–4.CrossRefGoogle ScholarPubMed

Knull, HR, Wells, WW. Recovery from galactose-induced neurotoxicity in the chick by the administration of glucose. J Neurochem 1973;20:415–22.CrossRefGoogle ScholarPubMed

Woolley, DW, Gommi, BW. Serotonin receptors, IV: specific deficiency of receptors in galactose poisoning and its possible relationship to the idiocy of galactosemia. Proc Natl Acad Sci USA 1964;52:14–19.CrossRefGoogle ScholarPubMed

Sanders, RD, Spencer, JB, Epstein, MP, et al. Biomarkers of ovarian function in girls and women with classic galactosemia. Fertil Steril 2009;92:344–51.CrossRefGoogle ScholarPubMed

Roe, TF, Hallat, JG, Donnell, GN, et al. Childbearing by a galactosemic woman. J Pediatr 1971;78:1026–30.CrossRefGoogle ScholarPubMed

Robbins, SL, Cotran, RS. (1979). Diseases of infancy and childhood. In Robbins, SL, Cotran, RS (Eds.), Pathologic Basis of Disease, 2nd edn. (p. 582). Philadelphia, PA: Saunders.Google Scholar

Smetana, HF, Olen, E. Hereditary galactose disease. Am J Clin Pathol 1962;38:3–25.CrossRefGoogle ScholarPubMed

Xu, YK, Kaufman, FR, Donnell, GN, et al. Radiochemical assay of minute quantities of galactose-1-phosphate uridyl transferase activity in erythrocytes and leukocytes of galactosemia patients. Clin Chim Acta 1995;235:125–36.CrossRefGoogle ScholarPubMed

Kliegman, RM, Sparks, JW. Perinatal galactose metabolism. J Pediatr 1985;107:831–41.CrossRefGoogle ScholarPubMed

Mellman, WJ, Tedesco, TA, Feige, P. Estimation of the gene frequency of the Duarte variant of galactose-1-phosphate uridyl transferase. Ann Hum Genet 1968;32:1.CrossRefGoogle Scholar

Brandt, NJ. Frequency of heterozygotes for hereditary galactosemia in a normal population. Acta Genet 1967;17:289.Google Scholar

Scriver, CR. Population screening: report of a workshop. Prog Clin Biol Res 1985;163B:89–152.Google ScholarPubMed

Pasquali, M, Yu, C, Coffee, B. Laboratory diagnosis of galactosemia: a technical standard and guideline of the American College of Medical Genetics and Genomics (ACMG). Genetics in Medicine 2018;1:3–11.CrossRefGoogle Scholar

Kleijer, WJ, Janse, HC, van Diggelen, OP, et al. First-trimester diagnosis of galactosaemia. Lancet 1986;i:748.CrossRefGoogle Scholar

Koch, R, Donnell, GN, Fishler, K, et al. Galactosemia. In Kelley, VC (ed.) Practice of Pediatrics. Hagerstown, MD: Harper & Row, 1979, p. 14.Google Scholar

Rubio-Gozalbo, ME, Haskovic, M, Bosch, AM, Burnyte, B, Coelho, AI, Cassiman, D, Couce, ML, Dawson, C. The natural history of classic galactosemia: lessons from the GalNet registry. Orphanet J Rare Dis 2019;1:86.CrossRefGoogle Scholar

Manis, FR, Cohn, LB, McBride-Chang, C, et al. A longitudinal study of cognitive functioning in patients with classical galactosaemia, including a cohort treated with oral uridine. J Inherit Metab Dis 1997;20:549–555.CrossRefGoogle ScholarPubMed

Berry, GT. The role of polyols in the pathophysiology of hypergalactosemia. Eur J Pediatr 1995;154(Suppl. 2):S53–S64.CrossRefGoogle ScholarPubMed

Boxer, MB, Shen, M, Tanega, C, et al. Toward improved therapy for classic galactosemia. Probe Reports from the NIH Molecular Libraries Program. Bethesda, MD: National Center for Biotechnology Information, 2010 (updated March 3, 2011).Google Scholar

Renner, C, Razeghi, S, Uberall, MA, et al. Hormone replacement therapy in galactosaemic twins with ovarian failure and severe osteoporosis. J Inherit Metab Dis 1999;22:194–5.CrossRefGoogle ScholarPubMed

Hennermann, JB, Schadewaldt, P, Vetter, B, et al. Features and outcome of galactokinase deficiency in children diagnosed by newborn screening. J Inherit Metab Dis 2011;34:399–407.CrossRefGoogle ScholarPubMed

Sangiuolo, F, Magnani, M, Stambolian, D, et al. Biochemical characterization of two GALK1 mutations in patients with galactokinase deficiency. Hum Mutat 2004;23:396.CrossRefGoogle ScholarPubMed

Sachs, B, Sternfeld, L, Kraus, G. Essential fructosuria: its pathophysiology. Am J Dis Child 1974;63:252.CrossRefGoogle Scholar

Steinmann, B, Gitzelmann, R, Van den Berghe, G. Disorders of fructose metabolism. In Scriver, C, Beaudet, A, Sly, W, et al. (eds.) The Metabolic and Molecular Bases of Inherited Disease, vol 1, 8th edn. New York: McGraw-Hill, 2000, pp. 1489–1520.Google Scholar

Chalmers, RA, Pratt, RTC. Idiosyncrasy to fructose. Lancet 1956;ii:340.Google Scholar

Froesch, ER, Prader, A, Labhart, A, et al. Hereditary fructose intolerance, a congenital metabolic disorder unknown until now.Schweiz Med Wochenschr 1957;87:1168–71.Google ScholarPubMed

Baker, L, Winegrad, AI. Fasting hypoglycemia and metabolic acidosis associated with deficiency of hepatic fructose-1,6-diphosphatase activity. Lancet 1970;ii:13–16.CrossRefGoogle Scholar

Thorens, B. Glucose transporters in the regulation of intestinal, renal, and liver glucose fluxes. Am J Physiol 1996;270:G541–53.Google ScholarPubMed

Rottmann, WH, Tolan, DR, Penhoet, EE. Complete amino acid sequence for human aldolase B derived from cDNA and genomic clones. Proc Natl Acad Sci USA 1984;81:2738–42.CrossRefGoogle ScholarPubMed