Laboratory Diagnosis of Inborn Errors of Liver Metabolism

doi:10.1017/9781108918978.024

Chapter 24 - Laboratory Diagnosis of Inborn Errors of Liver Metabolism

from Section IV - Metabolic Liver Disease

Published online by Cambridge University Press: 19 January 2021

Shawn McCandless

Edited by

Frederick J. Suchy ,

Ronald J. Sokol and

William F. Balistreri

Edited in association with

Jorge A. Bezerra ,

Cara L. Mack and

Benjamin L. Shneider

Show author details

Frederick J. Suchy: Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
Ronald J. Sokol: Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
William F. Balistreri: Affiliation:
Cincinnati Children’s Hospital Medical Center, Cincinnati
Jorge A. Bezerra: Affiliation:
Cincinnati Children’s Hospital Medical Center, Cincinnati
Cara L. Mack: Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
Benjamin L. Shneider: Affiliation:
Texas Children’s Hospital, Houston

Book contents

Get access

Summary

Liver disease due to inborn errors of metabolism (IEM) is relatively common, and this group of disorders is recognized with increasing frequency as a cause of disease at every life interval from the fetus to the geriatric patient. The specific patterns of disease, however, overlap with many other causes of liver disease. Specific testing for metabolites, or more recently through genomic sequencing, is required to appropriately diagnose these metabolic conditions, which increasingly have specific and effective treatments. The collective incidence of IEMs is often underestimated, and diagnostic errors often occur, leading to devastating consequences for patients and their families, including several historical examples of criminal charges against parents for child abuse and neglect [1].

Type: Chapter
Information: Liver Disease in Children , pp. 401 - 416

DOI: https://doi.org/10.1017/9781108918978.024 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2021

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

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.Google Scholar

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.Google Scholar

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

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

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

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.Google 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.CrossRef Google Scholar PubMed

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.2017.101CrossRef Google 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.CrossRef Google Scholar PubMed

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

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

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

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.Google Scholar

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.Google 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.CrossRef Google Scholar

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

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.CrossRef Google Scholar PubMed

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

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.Google Scholar

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

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.Google Scholar

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

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.Google Scholar

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

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

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.CrossRef Google Scholar PubMed

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

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

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.CrossRef Google Scholar PubMed

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.Google Scholar

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

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.Google Scholar

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.Google Scholar

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.Google Scholar

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.Google Scholar

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.Google 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 Scholar

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.Google Scholar

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

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.Google 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.Google Scholar

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.Google Scholar

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.Google Scholar

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.Google Scholar

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

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.Google Scholar

Book contents

Chapter 24 - Laboratory Diagnosis of Inborn Errors of Liver Metabolism

Summary

Access options

References

Save book to Kindle

Save book to Dropbox

Save book to Google Drive