Clinical Scenario:
A 10-year-old girl is referred from the ophthalmology department for preoperative pediatric and anesthesia assessment before surgery for lens subluxation. On examination, the pediatrician notes that she has a fair complexion and light-colored hair. She is tall and slender with long fingers, and her school performance has been below average.
Ophthalmologic examination reveals inferonasal subluxation of the lens.
Which of the following is the most likely diagnosis?
A. Marfan syndrome
B. Homocystinuria
C. Weill–Marchesani syndrome
D. Ehlers–Danlos syndrome
E. Isolated sulfite oxidase deficiency
Correct Answer & Explanation:
Correct answer: B. Homocystinuria
Explanation:
Homocystinuria should be considered in a child presenting with ectopia lentis, particularly when it is accompanied by a marfanoid habitus, arachnodactyly and developmental or learning difficulties. Classic homocystinuria may involve the ocular, skeletal, neurologic and vascular systems.
A particularly useful ophthalmologic distinction from Marfan syndrome is the direction of lens displacement. In homocystinuria, ectopia lentis is characteristically inferonasal, whereas Marfan syndrome classically produces superotemporal displacement. The inferonasal displacement in this case therefore supports homocystinuria.
The fair complexion and light-colored/coarse hair are additional clinical clues that can occur in homocystinuria.
The underlying disorder is associated with markedly elevated plasma total homocysteine, often accompanied by increased methionine. Confirmation is made with biochemical testing and, when appropriate, molecular testing.
Why not Marfan syndrome?
Both conditions can produce a marfanoid habitus, arachnodactyly and ectopia lentis, making Marfan syndrome the closest clinical differential. However, the inferonasal direction of lens subluxation, together with the other clinical clues in this case, favors homocystinuria.
Important clinical point
Homocystinuria is particularly important to recognize because affected patients have a significant risk of venous and arterial thromboembolism. This is clinically relevant when a child is being assessed before an ophthalmologic procedure.
Find high yield board review MCQs on Pediatric Endocrinology, Metabolic disorders & Genetics.
External Resources
1. GeneReviews — Homocystinuria due to Cystathionine Beta-Synthase Deficiency Read the GeneReviews chapter — comprehensive reference for clinical features, diagnosis, biochemical testing, and thromboembolic complications.
2. Merck Manual Professional — Methionine Metabolism Disorders Read the clinical review — summarizes the clinical overlap with Marfan syndrome and the vascular complications of classic homocystinuria.
3. MedlinePlus Genetics — Homocystinuria Read the genetics overview — covers inheritance, skeletal and ocular features, developmental difficulties, and clotting risk.
References
Sacharow SJ, Levy HL. Homocystinuria due to cystathionine beta-synthase deficiency. In: Adam MP, Bick S, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2026. Updated 2025 Sep 25.
Merck Manual Professional Edition. Methionine metabolism disorders.
MedlinePlus Genetics. Homocystinuria. Bethesda (MD): National Library of Medicine. Available from: https://www.medlineplus.gov/genetics/condition/homocystinuria/
