Homocystinuria
also see Marfan

• autosomal recessive
• rare disorder
• accumulation of homocysteine in the serum (cause of thrombotic events) and an increased excretion of homocysteine in the urine
• defect in methionine metabolism that is caused by a deficiency in cystathionine synthase (classic form). Other mechanisms include:
  • insufficient vitamin B-12 synthesis resulting from a defect in the remethylation of homocysteine to methionine; methylmalonic aciduria is present OR
  • deficiency in methylenetetrahydrofolate reductase. The methionine level is in the reference range.

Characteristics:

• (Phenotype in some ways similar to Marfan...)
• Developmental delay at age 2-3 years
• Ocular: downward lens subluxation (mnemonic: looking at urine), myopia
• Skeletal - slim, arachnodactyly (may appear late childhood, teenage years),  pectus excavatum, osteoporosis, tight joints
• Vascular - medial degeneration of aorta and elastic arteries; arterial and venous thromboses
• Derm: pale and pink skin
• Almost one fourth of patients die as a result of thrombotic complications (eg, heart attack) before they are aged 30 years.

Differences from Marfan syndrome:

• lax joints in Marfan; tight joints in homocystinuria
• lens dislocation - upward in Marfan, downward in homocystinuria
• aorta dilatation in Marfan
• thrombembolism, mental retardation, and psychiatric disturbance in homocystinuria
• inheritance (AD in Marfan, AR in homocystinuria)

CHLA Board Review 2005
Homocystinuria Last Updated: July 27, 2005  (Emedicine article)