Humpath.com - Human pathology

Home > D. General pathology > Genetic and developmental anomalies > Genetic metabolic diseases > homocystinuria

homocystinuria

MIM.236200 21q22.3

Friday 1 August 2008

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.