A 5-year-old boy with developmental delay is brought to the office due to difficulty "seeing the board" at school. Examination shows a boy with a tall, thin habitus with elongated limbs. Funduscopy shows bilateral lens subluxation. Four years later, the patient dies suddenly of a massive cerebrovascular accident. Autopsy shows middle cerebral artery thrombosis and old renal infarcts. His parents wish to know if anything could have been done to have prevented his death. Which of the following would have been the most appropriate supplementation for this patient?

Question

A 5-year-old boy with developmental delay is brought to the office due to difficulty "seeing the board" at school.  Examination shows a boy with a tall, thin habitus with elongated limbs.  Funduscopy shows bilateral lens subluxation.  Four years later, the patient dies suddenly of a massive cerebrovascular accident.  Autopsy shows middle cerebral artery thrombosis and old renal infarcts.  His parents wish to know if anything could have been done to have prevented his death.  Which of the following would have been the most appropriate supplementation for this patient?

Quizplus · Accepted Answer

11ec160b_36ca_6e26_9249_c9e148076af3_MD0001_00 This patient's presentation is most consistent with homocystinuria, the most common inborn error of methionine metabolism. Most patients present at age 3-10 with ectopia lentis (dislocated lens). About half of patients have intellectual disability. Other clinical manifestations include a Marfanoid habitus (eg, elongated limbs, arachnodactyly, scoliosis). Patients are at high risk for thromboembolic occlusion of both large and small vessels, especially those of the brain, heart, and kidneys. Thromboembolic complications are the major cause of morbidity and mortality in these patients. Homocystinuria is most frequently caused by an autosomal recessive deficiency of cystathionine beta-synthase, an enzyme that requires pyridoxine (vitamin B6) as a cofactor. Approximately 50% of affected patients respond to high doses of pyridoxine, which improves residual enzymatic activity and reduces plasma homocysteine levels. Additional treatment includes dietary restriction of methionine. (Choice A) Vitamin C is a necessary cofactor for the hydroxylation of proline and lysine residues in collagen. Vitamin C deficiency results in decreased strength of collagen fibers and causes scurvy. (Choice B) Carnitine assists with long-chain fatty acid transport into mitochondria. Deficiencies in carnitine (eg, primary systemic carnitine deficiency) lead to fatty acid oxidation defects in cardiac and skeletal muscle. (Choice D) Thiamine (vitamin B1) deficiency can cause dry and wet beriberi and Wernicke-Korsakoff syndrome. (Choice E) Tyrosine is a nonessential amino acid and the precursor for catecholamines such as dopamine, epinephrine, and norepinephrine. (Choice F) Vitamin K is involved in the post-translational conversion of glutamate to gamma-carboxyglutamic acid. This modification is necessary for the function of many clotting factors and regulatory proteins involved in the coagulation cascade. Educational objective: Homocystinuria is most commonly caused by cystathionine synthase deficiency. Affected individuals have marfanoid habitus, ectopia lentis, and developmental delay. Significant morbidity and mortality are due primarily to thromboembolism. Many patients with homocystinuria respond dramatically to pyridoxine (vitamin B6) supplementation. __________ References: Hypermethioninemias of genetic and non-genetic origin: A review. (http://www.ncbi.nlm.nih.gov/pubmed/21308989) Overview of homocysteine and folate metabolism. With special references to cardiovascular disease and neural tube defects. (http://www.ncbi.nlm.nih.gov/pubmed/20814827)

A 5-Year-Old Boy with Developmental Delay Is Brought to the Office