Homocysteinemia due to MTHFR deficiency in a young adult presenting with bilateral lens subluxations

ABSTRACT

The most common cause of isolated inherited homocysteinemia is a deficiency of the enzyme cystathionine β-synthase (CBS). Clinical manifestations of CBS deficiency can include ectopia lentis, thromboembolism, marfanoid habits, and intellectual disability. CBS deficiency, which affects the transsulfuration pathway, is marked biochemically by elevated serum homocysteine and plasma methionine. We report a patient with homocysteinemia, low plasma methionine, and no significant neurological abnormalities who presented with bilateral subluxated crystalline lenses due to a 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency. MTHFR deficiency, a disorder in the remethylation pathway, can cause mild to severe disease, although most presentations include neurological involvement. MTHFR deficiency has not been previously associated with lens subluxation or complete dislocation. Prolonged exposure to elevated serum homocysteine levels is most likely the explanation for her ectopia lentis. This case expands the differential diagnosis of homocysteinemia and highlights the need for a correct diagnosis to optimize the clinical outcome of patients with this condition.

KEYWORDS:

• 5, 10-methylenetetrahydrofolate reductase (MTHFR) deficiency
• crystalline lens subluxation or complete dislocation
• ectopia lentis
• homocysteinemia
• remethylation pathway
• transsulfuration pathway

Acknowledgments

We would like to thank the patient, her family, and all of the other providers who have participated in her care.

Declaration of interest

Natario L. Couser, MD, MS is a Principal Investigator at the University of North Carolina site for Retrophin, Inc., Protocol Number 018CTXX15001; An Observational, Multicenter Study of the Prevalence of Cerebrotendinous Xanthomatosis (CTX) in Patient Populations Diagnosed with Early-Onset Idiopathic Bilateral Cataracts. Dr. Couser is also a Co-Investigator at the University of North Carolina site for the Pediatric Eye Disease Investigator Group (PEDIG), funded by the National Eye Institute (NEI). The remaining authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Funding

The authors acknowledge support from an unrestricted grant from Research to Prevent Blindness (RPB), New York, NY to the University of North Carolina, Department of Ophthalmology.