Homocystinuria

Inheritance:

Autosomal recessive

Prevalence:

Estimated at 1/50,000 to 1/200,000

Locus:

21q22.3

Natural History:

Homocytinuria is caused by a deficiency in cystathione synthase (classic form), leading to the accumulation of homocysteine in the serum.. This leads to disorders of the connective tissue, muscles, central nervous system, and cardiovascular system. The condition is congenital and complications may occur before the first year of life. Approximately 25% of affected individuals die before 30 years due to thrombotic complications. About 50% of affected individuals are responsive to vitamin B6; course of illness is often more severe in vitamin B6 non-responders.

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Defining Characteristics:

Ocular

Progressive ectopia lentis

Severe myopia is the first sign of ectopia lentis (between 3-5 years old).

Lens dislocation down and in (typically between 4-10 years), cataracts, atrophy of optic nerve, glaucoma

Musculoskeletal

Marfan-like appearance, thin and long extremities, arachnodactyly, kyphoscoliosis, dolichostenomelia, pectus carinatum or excavatum

Mouth

High-arched palate, crowded teeth

Skin

Atrophic cigarette paper-like scars (arms and hands), hypopigmentation due to tyrosinase inhibition, coarse hair

Neurologic

Mental retardation (in about 50%), seizures, failure to thrive, developmental delay

Vascular

Fatal arterial and venous thromboses may occur, thromboembolism, stroke, severe hypertension

Heterozygotes: increased risk of thrombotic disease

Abdomen

Fatty changes in the liver, pancreatitis

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Psychiatric Characteristics

Abbott (1987): 51% of affected individuals have psychiatric disorders, including episodic depression (10%), chronic disorders of behavior (17%), chronic obsessive-compulsive disorder (5%), and personality disorders (19%).

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References:

Abbott, M.H., Folstein, S.E., Abbey, H., Pyeritz, R.E. Psychiatric manifestations of homocystinuria due to cystathionine beta-synthase deficiency: prevalence, natural history, and relationship to neurologic impairment and vitamin B6-responsiveness. Am J Med Genet 26: 959-969 (1987).

eMedicine
http://www.emedicine.com/derm/topic708.htm

PEDBASE
http://www.icondata.com/health/pedbase/files/HOMOCYST.HTM

OMIM
http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?236200

 

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