Clinical pattern, mutations and in vitro residual activity in 33 patients with severe 5, 10 methylenetetrahydrofolate reductase (MTHFR) deficiency

Autor: Patrick F. Chinnery, Carlo Dionisi-Vici, Adrian C. Sewell, Barbara Plecko, Jose M. Trejo-Gabriel-Galán, Ute Spiekerkoetter, Jürgen Christoph von Kleist-Retzow, Eugen Mengel, Patricie Burda, Megumi Tsuji, Regina Mulder-Bleile, Maria Antonia Vilaseca, Beat Steinmann, Brian Fowler, Rossella Parini, Alexander Lossos, Gülden Gökçay, Valerie Walker, Mübeccel Demirkol, Johannes Häberle, D. Sean Froese, Dariusz Rokicki, Andrew A. M. Morris, Bruria Ben Zeev, Grazia Taddeucci, Dries Dobbelaere, Jiri Zeman, Terttu Suormala, Wolfgang Sperl, Friedrich K. Trefz, Matthias R. Baumgartner, Mareike Schimmel, K. E. Niezen-Koning, Manuel Schiff, Martina Huemer
Přispěvatelé: Center for Liver, Digestive and Metabolic Diseases (CLDM)
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Homocysteine
Methylenetetrahydrofolate reductase deficiency
MR SPECTROSCOPY
Gastroenterology
chemistry.chemical_compound
Myelopathy
0302 clinical medicine
Methionine
BRAIN
Child
Genetics (clinical)
biology
3. Good health
Vitamin B 12
Phenotype
Muscle Spasticity
Female
Homocystinuria
medicine.symptom
medicine.medical_specialty
Ataxia
S-ADENOSYLMETHIONINE
METABOLISM
Cobalamin
Spinal Cord Diseases
Article
03 medical and health sciences
Folic Acid
CEREBROSPINAL-FLUID
ADULT
Internal medicine
Intellectual Disability
Genetics
medicine
Humans
Genetic Association Studies
Methylenetetrahydrofolate Reductase (NADPH2)
Retrospective Studies
business.industry
PARAPLEGIA
medicine.disease
Surgery
Betaine
030104 developmental biology
chemistry
Psychotic Disorders
Methylenetetrahydrofolate reductase
Mutation
biology.protein
business
030217 neurology & neurosurgery
FOLATE
Zdroj: JOURNAL OF INHERITED METABOLIC DISEASE
r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname
r-FSJD: Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
Fundació Sant Joan de Déu
Journal of inherited metabolic disease
Journal of Inherited Metabolic Disease, 39(1), 115-124. SPRINGER
ISSN: 0141-8955
Popis: BACKGROUND: Severe methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare (1.5% control) in vitro residual enzyme activity had mainly psychiatric symptoms, mental retardation, myelopathy, ataxia and spasticity. Treatment with various combinations of betaine, folate and cobalamin improved the biochemical and clinical phenotype. During the disease course, patients with very low enzyme activity showed a progression of feeding problems, neurological symptoms, mental retardation, and psychiatric disease while in patients with higher residual enzyme activity frequencies of myelopathy, ataxia and spasticity increased. All other symptoms remained stable or improved in both groups upon treatment as did brain imaging in some cases. No clear genotype-phenotype correlation was obvious. DISCUSSION: MTHFR deficiency is a severe disease primarily affecting the central nervous system. Age at first presentation and clinical pattern are correlated with low / higher in vitro residual enzyme activity. Treatment alleviates biochemical abnormalities and clinical symptoms partially.
Databáze: OpenAIRE
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