title: Severe scoliosis in a patient with severe methylenetetrahydrofolate reductase deficiency.
abstract: Severe methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessively inherited inborn error of folate metabolism. We report a new patient with severe MTHFR deficiency who presented at age 4 months with early onset severe scoliosis associated with severe hypotonia. Markedly decreased MTHFR enzyme activity (0.3 nmoles CHO/mg protein/h; reference range>9) and compound heterozygous mutations (c. 1304T>C; p.Phe435Ser and c.1539dup; p.Glu514Argfs∗24) in the MTHFR gene confirmed the diagnosis. She was treated with vitamin B12, folic acid and betaine supplementation and showed improvements in her developmental milestones and hypotonia. To the best of our knowledge, this is the first patient with MTHFR deficiency reported with severe early onset scoliosis. Despite the late diagnosis and treatment initiation, she showed favorable short-term neurodevelopmental outcome. This case suggests that homocysteine measurement should be included in the investigations of patients with developmental delay, hypotonia and scoliosis within first year of life prior to organizing genetic investigations.
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Munoz
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Jinesh
authors.initials: J
authors.lastname: Patel
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Ramses
authors.initials: R
authors.lastname: Badilla-Porras
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kronick
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada; Genetics and Genome Biology Program, Research Institute, The Hospital for Sick Children, Toronto, Canada. Electronic address: saadet.mahmutoglu@sickkids.ca.
authors.forename: Saadet
authors.initials: S
authors.lastname: Mercimek-Mahmutoglu
mesh_terms: D002675:Child, Preschool; D005260:Female; D006712:Homocystinuria / Q000150:complications*; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000172:deficiency*; D009128:Muscle Spasticity / Q000150:complications*; D011618:Psychotic Disorders / Q000150:complications; D012600:Scoliosis / Q000209:etiology*
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: Failure to thrive; Homocysteine; Hypotonia; Scoliosis; Severe methylenetetrahydrofolate reductase deficiency