Clinical pattern, mutations and in vitro residual activity in 33 patients with severe 5, 10 methylenetetrahydrofolate reductase (MTHFR) deficiency.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
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Huemer Martina, Mulder-Bleile Regina, Burda Patricie, Froese D Sean, Suormala Terttu, Zeev Bruria Ben, Chinnery Patrick F, Dionisi-Vici Carlo, Dobbelaere Dries, Gökcay Gülden, Demirkol Mübeccel, Häberle Johannes, Lossos Alexander, Mengel Eugen, Morris Andrew A, Niezen-Koning Klary E, Plecko Barbara, Parini Rossella, Rokicki Dariusz, Schiff Manuel, Schimmel Mareike, Sewell Adrian C, Sperl Wolfgang, Spiekerkoetter Ute, Steinmann Beat, Taddeucci Grazia, Trejo-Gabriel-Galán Jose M, Trefz Friedrich, Tsuji Megumi, Vilaseca María Antònia, von Kleist-Retzow Jürgen-Christoph, Walker Valerie, Zeman Jiri, Baumgartner Matthias R, Fowler Brian
Аннотация
METHODS: Clinical, biochemical and treatment data was obtained from physicians by using a questionnaire. MTHFR activity was measured in primary fibroblasts; genomic DNA was extracted from cultured fibroblasts.
RESULTS: Thirty-three patients (mean age at follow-up 11.4 years; four deceased; median age at first presentation 5 weeks; 17 females) were included. Patients with very low (<1.5%) mean control values of enzyme activity (n = 14) presented earlier and with a pattern of feeding problems, encephalopathy, muscular hypotonia, neurocognitive impairment, apnoea, hydrocephalus, microcephaly and epilepsy. Patients with higher (>1.7-34.8%) residual enzyme activity had mainly psychiatric symptoms, mental retardation, myelopathy, ataxia and spasticity. Treatment with various combinations of betaine, methionine, 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, 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 presentation and clinical pattern are correlated with residual enzyme activity. Treatment alleviates biochemical abnormalities and clinical symptoms partially.