Homocystinuria due to cystathionine β-synthase deficiency: Novel biochemical findings and treatment efficacy

M. Orendáč, J. Zeman, S. P. Stabler, R. H. Allen, J. P. Kraus, O. Bodamer, S. Stöckler-Ipsiroglu, J. Kvasnička, V. Kožich

Research output: Contribution to journalArticle

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Abstract

To explore the pathogenesis of cystathionine β-synthase (CBS) deficiency and to test the efficacy of pharmacological therapy we examined a panel of metabolites in nine homocystinuric patients under treated and/or untreated conditions. Off pharmacological treatment, the biochemical phenotype was characterized by accumulation of plasma total homocysteine (median 135 μmol/L) and blood S-adenosylhomocysteine (median 246 nmol/L), and by normal levels of guanidinoacetate and creatine. In addition, enhanced remethylation was demonstrated by low serine level (median 81 μmol/L), and by increased concentration of methionine (median 76 μmol/L) and N-methylglycine (median 6.8 μmol/L). Despite the substantially blocked transsulphuration, which was evidenced by undetectable cystathionine and severely decreased total cysteine levels (median 102 μmol/L), blood glutathione was surprisingly not depleted (median 1155 μmol/L). In 5 patients in whom pharmacological treatment was withdrawn, the differences of median plasma total homocysteine levels (125 μmol/L after withdrawal versus 33 μmol/L under treatment conditions), total cysteine levels (139 versus 211 μmol/L) and plasma serine levels (53 versus 103 μmol/L) on and off treatment demonstrated the efficacy of long-term pyridoxine/betaine administration (p < 0.05). The treatment also decreased blood S-adenosylhomocysteine level (133 versus 59 nmol/L) with a borderline significance. In summary, our study shows that conventional treatment of CBS deficiency by diet and pyridoxine/betaine normalizes many but not all metabolic abnormalities associated with CBS deficiency. We propose that the finding of low plasma serine concentration in untreated CBS-deficient patients merits further exploration since supplementation with serine might be a novel and safe component of treatment of homocystinuria.

Original languageEnglish
Pages (from-to)761-773
Number of pages13
JournalJournal of Inherited Metabolic Disease
Volume26
Issue number8
DOIs
StatePublished - Dec 1 2003

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Cystathionine
Homocystinuria
Serine
S-Adenosylhomocysteine
Betaine
Pyridoxine
Homocysteine
Pharmacology
Therapeutics
Cysteine
Sarcosine
Creatine
Methionine
Glutathione
Diet
Phenotype

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics
  • Endocrinology

Cite this

Homocystinuria due to cystathionine β-synthase deficiency : Novel biochemical findings and treatment efficacy. / Orendáč, M.; Zeman, J.; Stabler, S. P.; Allen, R. H.; Kraus, J. P.; Bodamer, O.; Stöckler-Ipsiroglu, S.; Kvasnička, J.; Kožich, V.

In: Journal of Inherited Metabolic Disease, Vol. 26, No. 8, 01.12.2003, p. 761-773.

Research output: Contribution to journalArticle

Orendáč, M, Zeman, J, Stabler, SP, Allen, RH, Kraus, JP, Bodamer, O, Stöckler-Ipsiroglu, S, Kvasnička, J & Kožich, V 2003, 'Homocystinuria due to cystathionine β-synthase deficiency: Novel biochemical findings and treatment efficacy', Journal of Inherited Metabolic Disease, vol. 26, no. 8, pp. 761-773. https://doi.org/10.1023/B:BOLI.0000009963.88420.c2
Orendáč, M. ; Zeman, J. ; Stabler, S. P. ; Allen, R. H. ; Kraus, J. P. ; Bodamer, O. ; Stöckler-Ipsiroglu, S. ; Kvasnička, J. ; Kožich, V. / Homocystinuria due to cystathionine β-synthase deficiency : Novel biochemical findings and treatment efficacy. In: Journal of Inherited Metabolic Disease. 2003 ; Vol. 26, No. 8. pp. 761-773.
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AU - Orendáč, M.

AU - Zeman, J.

AU - Stabler, S. P.

AU - Allen, R. H.

AU - Kraus, J. P.

AU - Bodamer, O.

AU - Stöckler-Ipsiroglu, S.

AU - Kvasnička, J.

AU - Kožich, V.

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