homocystinuria

Definition: Homocystinuria is a autosomal recessive metabolic disorder due to cystathionine beta-synthase (EC 4.2.1.22) deficiency producing increased urinary homocystine and methionine. Major clinical manifestations involve the eyes and the central nervous, skeletal, and vascular systems.

Clinical synopsis

 normal to tall stature
 occasional failure to thrive in infancy
 ectopia lentis
 myopia
 glaucoma
 ectopia lentis (90%)
 high arched palate
 crowded teeth
 myocardial infarction
 mitral valve prolapse
 pectus excavatum
 pectus carinatum
 nearsightedness
 flush across the cheeks
 tall, thin build
 long limbs
 high-arched feet (pes cavus)
 knock-knees (genu valgum)
 mental retardation
 psychiatric disease
 myopia
 optic atrophy
 seizure
 extensive atheroma formation at young age which affects many arteries but not the coronary arteries
 inguinal hernia
 fatty changes in liver
 pancreatitis
 generalized osteoporosis
 biconcave ’codfish’ vertebrae
 kyphoscoliosis
 oolichostenomelia
 arachnodactyly
 limited joint mobility
 fine, brittle hair
 seizures
 cerebrovascular accident
 thromboembolism

LABORATORY

 homocystinuria
 methioninuria

Etiology

 cystathionine beta-synthase deficiency

Therapeutis and management

 Fifty-percent of individuals responsive to pyridoxine (vitamin B6)
 Pyridoxine responsive individuals often have milder manifestations than those not responsive
 Management of homocystinuria includes low methionine, cystine supplemented diet for pyridoxine nonresponders and pyridoxine supplementation for pyridoxine responders
 Treatment with betaine, especially for pyridoxine nonresponders.