Book contents
- Frontmatter
- Contents
- Contributors
- Foreword
- Preface
- 1 Introduction
- 2 Genetics of neurocutaneous disorders
- 3 Clinical recognition
- 4 Neurofibromatosis type 1
- 5 Neurofibromatosis type 2
- 6 Tuberous sclerosis complex
- 7 von Hippel–Lindau disease
- 8 Neurocutaneous melanosis
- 9 Nevoid basal cell carcinoma (Gorlin) syndrome
- 10 Epidermal nevus syndromes
- 11 Multiple endocrine neoplasia type 2
- 12 Ataxia–telangiectasia
- 13 Incontinentia pigmenti
- 14 Hypomelanosis of Ito
- 15 Cowden disease
- 16 Pseudoxanthoma elasticum
- 17 Ehlers–Danlos syndromes
- 18 Hutchinson–Gilford progeria syndrome
- 19 Blue rubber bleb nevus syndrome
- 20 Hereditary hemorrhagic telangiectasia (Osler–Weber–Rendu)
- 21 Hereditary neurocutaneous angiomatosis
- 22 Cutaneous hemangiomas: vascular anomaly complex
- 23 Sturge–Weber syndrome
- 24 Lesch–Nyhan syndrome
- 25 Multiple carboxylase deficiency
- 26 Homocystinuria due to cystathionine β-synthase (CBS) deficiency
- 27 Fucosidosis
- 28 Menkes disease
- 29 Xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy
- 30 Cerebrotendinous xanthomatosis
- 31 Adrenoleukodystrophy
- 32 Peroxisomal disorders
- 33 Familial dysautonomia
- 34 Fabry disease
- 35 Giant axonal neuropathy
- 36 Chediak–Higashi syndrome
- 37 Encephalocraniocutaneous lipomatosis
- 38 Cerebello-trigemino-dermal dysplasia
- 39 Coffin–Siris syndrome: clinical delineation; differential diagnosis and long-term evolution
- 40 Lipoid proteinosis
- 41 Macrodactyly–nerve fibrolipoma
- Index
- References
26 - Homocystinuria due to cystathionine β-synthase (CBS) deficiency
Published online by Cambridge University Press: 31 July 2009
- Frontmatter
- Contents
- Contributors
- Foreword
- Preface
- 1 Introduction
- 2 Genetics of neurocutaneous disorders
- 3 Clinical recognition
- 4 Neurofibromatosis type 1
- 5 Neurofibromatosis type 2
- 6 Tuberous sclerosis complex
- 7 von Hippel–Lindau disease
- 8 Neurocutaneous melanosis
- 9 Nevoid basal cell carcinoma (Gorlin) syndrome
- 10 Epidermal nevus syndromes
- 11 Multiple endocrine neoplasia type 2
- 12 Ataxia–telangiectasia
- 13 Incontinentia pigmenti
- 14 Hypomelanosis of Ito
- 15 Cowden disease
- 16 Pseudoxanthoma elasticum
- 17 Ehlers–Danlos syndromes
- 18 Hutchinson–Gilford progeria syndrome
- 19 Blue rubber bleb nevus syndrome
- 20 Hereditary hemorrhagic telangiectasia (Osler–Weber–Rendu)
- 21 Hereditary neurocutaneous angiomatosis
- 22 Cutaneous hemangiomas: vascular anomaly complex
- 23 Sturge–Weber syndrome
- 24 Lesch–Nyhan syndrome
- 25 Multiple carboxylase deficiency
- 26 Homocystinuria due to cystathionine β-synthase (CBS) deficiency
- 27 Fucosidosis
- 28 Menkes disease
- 29 Xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy
- 30 Cerebrotendinous xanthomatosis
- 31 Adrenoleukodystrophy
- 32 Peroxisomal disorders
- 33 Familial dysautonomia
- 34 Fabry disease
- 35 Giant axonal neuropathy
- 36 Chediak–Higashi syndrome
- 37 Encephalocraniocutaneous lipomatosis
- 38 Cerebello-trigemino-dermal dysplasia
- 39 Coffin–Siris syndrome: clinical delineation; differential diagnosis and long-term evolution
- 40 Lipoid proteinosis
- 41 Macrodactyly–nerve fibrolipoma
- Index
- References
Summary
Introduction
Homocystinuria due to cystathionine β-synthase (CBS) deficiency (MIM # 236200) is the most common inborn error of sulfur amino acid metabolism. It is inherited as an autosomal recessive trait. The frequency of the disease has been estimated between 1 in 200 000 and 1 in 335 000 (Mudd et al., 1989), though several lines of evidence indicate that this frequency might be higher (Mudd et al., 1995).
Sulfur-containing amino acids, homocysteine, methionine and cysteine are linked by the remethylation cycle and the trans-sulfuration pathway (Fig. 26.1). CBS (shape l-serine hydrolyase; EC 4.2.1.22) catalyzes the condensation of homocysteine with serine to form the thioether cystathionine, a reaction requiring pyridoxal-phosphate as cofactor (Fig. 26.1, enzyme 2). Cystathionine is cleaved to cysteine and α-ketobutyrate by another pyridoxal-phosphate-dependent enzyme, γ-cystathionase (enzyme 3). The trans-sulfuration pathway ends converting sulfite to sulfate and is catalyzed by sulfite oxidase (enzyme 4), requiring a molybdenum cofactor. Conversion of methionine into homocysteine proceeds via methionine adenosyltransferase (enzyme 1) yielding S-adenosylmethionine, a methyl-group donor used in several transmethylation reactions, and S-adenosylhomocystein e, which is cleaved to adenosine and homocysteine. About 50% of homocysteine, not entering the trans-sulfuration pathway, is recycled into methionine. This step involves methyl transfer either from 5-methyl-tetrahydrofolate (THF), catalyzed by cobalamin-requiring 5-methyl THF-homocystei ne methyltransferase (methionine synthase, MS, enzyme 5), or from betaine, catalyzed by betaine-homocysteine methyltransferase (enzyme 6).
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- Information
- Neurocutaneous Disorders , pp. 206 - 213Publisher: Cambridge University PressPrint publication year: 2004