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 In 5 patients in whom pharmacological treatment was withdrawn, the differences of median plasma total homocysteine levels (125 μmol/L after withdrawal versus 33 μmol/L under treatment conditions), total cysteine levels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 language | English |
|---|---|
| Pages (from-to) | 761-773 |
| Number of pages | 13 |
| Journal | Journal of Inherited Metabolic Disease |
| Volume | 26 |
| Issue number | 8 |
| DOIs | |
| State | Published - Dec 1 2003 |
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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 journal › Article
}
TY - JOUR
T1 - Homocystinuria due to cystathionine β-synthase deficiency
T2 - Novel biochemical findings and treatment efficacy
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.
PY - 2003/12/1
Y1 - 2003/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0942266395&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0942266395&partnerID=8YFLogxK
U2 - 10.1023/B:BOLI.0000009963.88420.c2
DO - 10.1023/B:BOLI.0000009963.88420.c2
M3 - Article
C2 - 14739681
AN - SCOPUS:0942266395
VL - 26
SP - 761
EP - 773
JO - Journal of Inherited Metabolic Disease
JF - Journal of Inherited Metabolic Disease
SN - 0141-8955
IS - 8
ER -