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

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39 Scopus citations


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 In 5 patients in whom pharmacological treatment was withdrawn, the differences of median plasma total homocysteine levels (125 μmol/L after withdrawal versus 33 μmol/L under treatment conditions), total cysteine levels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 (US)
Pages (from-to)761-773
Number of pages13
JournalJournal of Inherited Metabolic Disease
Issue number8
StatePublished - 2003
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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