Molecular and biochemical investigations of patients with intermediate or severe hyperhomocysteinemia

A discrepancy has been identified between numbers of expected and identified patients with homocystinuria due to cystathionine beta-synthase (CBS) deficiency. Patients homozygous for the frequent c.833T>C (p.I278T) are most often responsive to vitamin B6, and can present with a total-homocysteine...

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Bibliographic Details
Published in:Molecular genetics and metabolism 2016-03, Vol.117 (3), p.344-350
Main Authors: Sørensen, Jannie Tanderup, Gaustadnes, Mette, Stabler, Sally P., Allen, Robert H., Mudd, S. Harvey, Hvas, Anne-Mette
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Base Sequence
Bone Density
Cystathionine beta-Synthase - blood
Cystathionine beta-Synthase - deficiency
Cystathionine beta-Synthase - genetics
Denmark - epidemiology
Female
Follow-Up Studies
Genotype
Heterozygote
Homocysteine - blood
Homocystinuria
Homocystinuria - etiology
Homocystinuria - metabolism
Homozygote
Humans
Hyperhomocysteinemia
Hyperhomocysteinemia - blood
Hyperhomocysteinemia - epidemiology
Hyperhomocysteinemia - genetics
Hyperhomocysteinemia - metabolism
Male
Methylenetetrahydrofolate reductase
Methylenetetrahydrofolate Reductase (NADPH2) - genetics
Middle Aged
Mutation
Polymorphism, Genetic
Prevalence
Thromboembolism - etiology
Thrombosis
Young Adult
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Summary:A discrepancy has been identified between numbers of expected and identified patients with homocystinuria due to cystathionine beta-synthase (CBS) deficiency. Patients homozygous for the frequent c.833T>C (p.I278T) are most often responsive to vitamin B6, and can present with a total-homocysteine (tHcy) C (p.I278T), and four were compound heterozygous for c.833T>C. One c.833T>C (p.I278T) compound heterozygote was identified by lowering the threshold for sequencing from tHcy at 100μM to 50μM. The most prominent clinical presentation among patients with a CBS2 mutation was thrombosis presenting at a median age of 25years. In case of arterial or venous thrombosis without any explanation in individuals below 40years, tHcy should be part of the thrombophilia screening. When tHcy is between 50 and 100μM genotyping for the MTHFR3 c.677TT is relevant, and when tHcy >100μM CBS should be genotyped. •We studied genetic causes and clinical history of patients with homocysteine ≥50μM.•Eighty-seven patients (49%) had the MTHFR c.677TT genotype.•CBS mutations were present in seven (18%) of the patients with homocysteine ≥100μM.•One compound heterozygote patient was identified with homocysteine
ISSN:1096-7192
1096-7206
DOI:10.1016/j.ymgme.2015.12.010