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

Ophthalmic Genet. 2017 Jan-Feb;38(1):91-94. doi: 10.3109/13816810.2016.1143017. Epub 2016 Apr 4.

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Betaine / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Homocysteine / blood
  • Homocystinuria / complications*
  • Homocystinuria / diagnosis
  • Homocystinuria / drug therapy
  • Humans
  • Hyperhomocysteinemia / diagnosis
  • Hyperhomocysteinemia / drug therapy
  • Hyperhomocysteinemia / etiology*
  • Lens Subluxation / diagnosis
  • Lens Subluxation / etiology*
  • Leucovorin / therapeutic use
  • Lipotropic Agents / therapeutic use
  • Methionine / blood
  • Methylenetetrahydrofolate Reductase (NADPH2) / deficiency*
  • Muscle Spasticity / complications*
  • Muscle Spasticity / diagnosis
  • Muscle Spasticity / drug therapy
  • Polymorphism, Single Nucleotide
  • Psychotic Disorders / complications
  • Psychotic Disorders / diagnosis
  • Psychotic Disorders / drug therapy
  • Tetrahydrofolates / deficiency*
  • Tetrahydrofolates / genetics
  • Vitamin B Complex / therapeutic use

Substances

  • Lipotropic Agents
  • Tetrahydrofolates
  • Homocysteine
  • 5,10-methylenetetrahydrofolic acid
  • Vitamin B Complex
  • Betaine
  • Methionine
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Leucovorin

Supplementary concepts

  • Homocysteinemia
  • Methylenetetrahydrofolate reductase deficiency