OMIM ID:
Homocystinuria, MTHFR Deficiency
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
The ocular signs in MTHFR deficiency are likely similar to those found in beta-synthase deficiency (236200) but no comparative study has been reported. Ectopia lentis is common and the high mobility of the lens carries a significant risk of pupillary block glaucoma and migration into the anterior chamber.
Systemic Features
There is a wide range in clinical disease in MTHFR deficiency but the neurological signs and the progressive of disease seem to be more aggressive than in beta-synthase deficiency (236200) . Neonates may have seizures and failure to thrive but other affected patients may live to adulthood without symptoms. Early death from neurological complications is more common and the mental retardation is apparently more severe. There is a serious risk for thromboembolic events which may be life-threatening. Hyperhomocyteinemia and low plasma methionine are present as is increased homocystine in urine.
Genetics
Inheritance
Mutations in MTHFR (1p36.3) are responsible for this form of homocystinuria. Another form, beta-synthase deficiency (236200), is caused by a mutation in the CBS gene (21q22.3). This is an autosomal recessive disorder.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.