title: 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.
authors.affiliation: a Department of Ophthalmology , University of North Carolina School of Medicine , Chapel Hill , NC , USA.|b Department of Pediatrics, Division of Genetics and Metabolism , University of North Carolina School of Medicine , Chapel Hill , NC , USA.
authors.forename: Natario L
authors.initials: NL
authors.lastname: Couser
authors.affiliation: b Department of Pediatrics, Division of Genetics and Metabolism , University of North Carolina School of Medicine , Chapel Hill , NC , USA.
authors.forename: Julie
authors.initials: J
authors.lastname: McClure
authors.affiliation: c Cornerstone Eye Care, High Point , NC , USA.|d Department of Ophthalmology , Wake Forest University School of Medicine , Winston-Salem , NC , USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Evans
authors.affiliation: d Department of Ophthalmology , Wake Forest University School of Medicine , Winston-Salem , NC , USA.
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Haines
authors.affiliation: d Department of Ophthalmology , Wake Forest University School of Medicine , Winston-Salem , NC , USA.
authors.forename: Susan K
authors.initials: SK
authors.lastname: Burden
authors.affiliation: b Department of Pediatrics, Division of Genetics and Metabolism , University of North Carolina School of Medicine , Chapel Hill , NC , USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Muenzer
mesh_terms: D000328:Adult; D001622:Betaine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006710:Homocysteine / Q000097:blood; D006712:Homocystinuria / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy; D006801:Humans; D020138:Hyperhomocysteinemia / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology*; D007906:Lens Subluxation / Q000175:diagnosis / Q000209:etiology*; D002955:Leucovorin / Q000627:therapeutic use; D008082:Lipotropic Agents / Q000627:therapeutic use; D008715:Methionine / Q000097:blood; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000172:deficiency*; D009128:Muscle Spasticity / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy; D020641:Polymorphism, Single Nucleotide; D011618:Psychotic Disorders / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy; D013763:Tetrahydrofolates / Q000172:deficiency* / Q000235:genetics; D014803:Vitamin B Complex / Q000627:therapeutic use
chemical_list: D008082:Lipotropic Agents; D013763:Tetrahydrofolates; D006710:Homocysteine; C013123:5,10-methylenetetrahydrofolic acid; D014803:Vitamin B Complex; D001622:Betaine; D008715:Methionine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D002955:Leucovorin
keywords: 5, 10-methylenetetrahydrofolate reductase (MTHFR) deficiency; crystalline lens subluxation or complete dislocation; ectopia lentis; homocysteinemia; remethylation pathway; transsulfuration pathway