Are heterocygotes for classical homocystinuria at risk of vitamin B12 and folic acid deficiency?
OBJECTIVE
Comparative cross-sectional study to assess homocysteine and vitamin status in carriers of CBS gene mutations.


METHODS
Subjects included 34 parents (13 males, 21 females, age 27-59 years) of 30 patients with classical homocystinuria due to homozygous cystathionine beta-synthase deficiency. Control subjects were matched for gender and age (13 males, 21 females, age 25-59 years). All subjects were of Qatari origin, had normal liver and renal function tests and had not taken drugs or vitamin supplements prior to the study. The concentrations of homocysteine, folic acid and vitamins B6 and B12 in blood were determined after an overnight fast.


RESULTS
Heterozygous carriers had significantly increased fasting levels of homocysteine compared to controls (9.1 vs. 8.1 micromol/l, P=0.012). Both folic acid (328 vs. 478 pmol/l, P=0.002) and vitamin B12 concentrations (232 vs. 287 pmol/l, P=0.013) were reduced whilst there was no significant difference in vitamin B6 levels between the two groups (5.8 vs. 6.44 microg/l).


CONCLUSIONS
Increased homocysteine concentrations in CBS gene mutation carriers are associated with reduced concentrations of folic acid and vitamin B12 in blood. In view of the adverse effects of mild hyperhomocysteinemia, routine testing of vitamin status in parents of homocystinuria patients may be warranted. The causal relationship and pathophysiological consequences are uncertain; it is likely that CBS gene mutation carriers need higher doses of dietary vitamins.
Department of Pediatrics Neurology Unit, Hamad General Hospital, Hamad Medical Corporation, Qatar, and Department of Evidence for Population Health Unit, School of Epidemiology and Health Sciences, The University of Manchester, UK.
Mahmoud F
MF
Elsaid
Abdulbari
A
Bener
Martin
M
Lindner
Mahmoud
M
Alzyoud
Noora
N
Shahbek
Mohammed O
MO
Abdelrahman
Ghassan
G
Abdoh
Mohammed S
MS
Bessisso
Johannes
J
Zschocke
Georg F
GF
Hoffmann
D000328:Adult; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003541:Cystathionine beta-Synthase / Q000172:deficiency / Q000235:genetics; D005260:Female; D005492:Folic Acid / Q000097:blood; D005494:Folic Acid Deficiency / Q000097:blood / Q000235:genetics*; D006579:Heterozygote; D006710:Homocysteine / Q000097:blood; D006712:Homocystinuria / Q000097:blood / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D012307:Risk Factors; D014805:Vitamin B 12 / Q000097:blood; D014806:Vitamin B 12 Deficiency / Q000097:blood / Q000235:genetics*; D025101:Vitamin B 6 / Q000097:blood
D006710:Homocysteine; D025101:Vitamin B 6; D005492:Folic Acid; D003541:Cystathionine beta-Synthase; D014805:Vitamin B 12