Homocystinuria (classical)
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A tall teenager with intellectual disability has downward lens dislocation (ectopia lentis). He had a stroke at age 15. Homocysteine is markedly elevated.
AR; CBS (cystathionine beta-synthase)
- Ocular: Ectopia lentis (downward - opposite of Marfan)
- Skeletal: Marfanoid habitus, osteoporosis
- Vascular: Thromboembolism (stroke, PE)
- CNS: Intellectual disability, psychiatric symptoms
- On RUSP
- Newborn screening (RUSP) flags elevated methionine on tandem mass spectrometry (low sensitivity for B6-responsive disease)
- Plasma amino acids: elevated total homocysteine and methionine with low/normal cysteine; elevated urinary homocystine
- Reduced cystathionine beta-synthase activity in cultured fibroblasts
- Confirmatory CBS molecular testing
- B6 (pyridoxine) - some patients responsive; methionine-restricted diet, betaine
The methionine-to-cysteine pathway shows the role of cystathionine beta-synthase (CBS) and its cofactor vitamin B6 in homocysteine metabolism.
HOMOCY = increased Homocysteine in urine, Osteoporosis, Marfanoid habitus, Ocular changes (downward lens subluxation), Cardiovascular effects (thrombosis, atherosclerosis), kYphosis.
"Homer Simpson & Marge Simpson on CBS news": classical homocystinuria is caused by mutations in CBS (cystathionine beta-synthase).
Lens down in homocystinuria, lens up in Marfan: "look down at your homo(cysteine)" versus "look up toward Mars (Marfan)." VTE + intellectual disability = think homocystinuria.