Homocystinuria Flashcards
A 12-year-old boy presents with vision problems, frequent falls, and a history of delayed developmental milestones. On examination, he has long, slender limbs, kyphosis, and downward and inward dislocation of the lenses. Laboratory studies reveal elevated homocysteine levels in the urine. Which of the following treatments is most appropriate if the underlying defect is cystathionine synthase deficiency?
A) Increase methionine and folate in the diet
B) Supplement folate and vitamin B12, and restrict methionine intake
C) Increase cysteine in the diet and supplement vitamin B6
D) Supplement thiamine and avoid branched-chain amino acids
E) Restrict tyrosine and supplement phenylalanine
Answer: Increase cysteine in the diet and supplement vitamin B6
Explanation: Cystathionine synthase deficiency, the most common cause of homocystinuria, leads to the accumulation of homocysteine. Treatment involves increasing cysteine (which becomes an essential amino acid in this condition), reducing methionine intake, and supplementing pyridoxine (vitamin B6), a cofactor for the enzyme. This approach reduces homocysteine levels and mitigates the risk of complications such as thromboembolic events and lens dislocation.
Incorrect Answers:
A) Increasing methionine is appropriate for methionine synthase deficiency but would worsen cystathionine synthase deficiency.
B) Folate and vitamin B12 supplementation are needed for MTHFR or methionine synthase deficiencies, not cystathionine synthase deficiency.
D) Thiamine supplementation and branched-chain amino acid restriction are treatments for maple syrup urine disease, not homocystinuria.
E) Tyrosine restriction is used in tyrosinemia, and phenylalanine supplementation is used in tyrosine hydroxylase deficiency, not in homocystinuria.
What is the genetic inheritance pattern of Homocystinuria?
Autosomal recessive
What are the main enzymatic defects that cause Homocystinuria?
Deficiency of cystathionine synthase, methionine synthase, or MTHFR (methylene tetrahydrofolate reductase)
What is the most common cause of Homocystinuria?
Cystathionine synthase deficiency
What are the clinical features of Homocystinuria?
HOMOCYstinuria:
Homocysteine in urine.
Osteoporosis.
Marfanoid habitus.
Ocular changes (downward and inward lens subluxation).
Cardiovascular effects (thrombosis and atherosclerosis stroke and MI).
kYphosis and scoliosis.
intellectual disability.
hypopigmented skin (fair complexion).
Marfanoid habitus means that patients tend to have long limbs, with hypermobile joints, arachnodactyly, pectus deformity, high arched palates, and hyperelastic skin.
How does lens subluxation in Homocystinuria differ from Marfan syndrome?
Lens subluxes downward and inward in Homocystinuria.
upward and outward in Marfan syndrome.
What are the cardiovascular risks associated with Homocystinuria?
Increased risk of thrombosis and atherosclerosis leading to stroke and myocardial infarction
Patients require anticoagulation.
What is the diagnostic for Homocystinuria?
A deficiency in cystathionine synthase leads to excessive homocysteine in the blood and urine; the addition of sodium nitroprusside will turn these patients’ urine a deep red color, confirming the presence of homocysteine and will establish the diagnosis.
What dietary modifications are recommended for managing cystathionine synthase deficiency in Homocystinuria?
Homocystinuria due to cystathionine synthase deficiency is treated with a low methionine, high cysteine diet, and supplementation with vitamin B12 and folate (vitamin B9).
Some patients respond well to large doses of pyridoxine (vitamin B6).
What treatments are used for methionine synthase or MTHFR deficiencies in Homocystinuria?
Methionine supplementation for methionine synthase deficiency.
folate supplementation for MTHFR deficiency.
No matter what the underlying cause for a patient’s Homocystinuria, what intervention is needed for every patient of this disease?
Anticoagulation/Anti-platelets
