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The clinical signs are mainly neurological, and hematological signs are seen in CblE, CblG, and CblD\u2010variant\u20101 defects. Patients with neonatal or early\u2010onset disease exhibit acute neurological distress. Infants and children have unspecific mental retardation, often with acquired microcephaly. Without appropriate therapy, they may experience acute or rapidly progressive neurological deterioration, which may be fatal. Adolescents and adults show normal development or mild developmental delay initially and then experience rapid neurological or behavioral deterioration. A few patients may have signs of subacute combined degeneration of the spinal cord. Adults may be asymptomatic or present with isolated thromboembolism. All patients with suspected remethylation disorders should receive emergency treatment with parenteral administration of hydroxocobalamin and folate supplements combined with betaine orally. The long\u2010term treatment of CblE, CblG, and CblD\u2010variant\u20101 defects consists of parenterally administered hydroxocobalamin and orally administered folate and betaine supplements, whereas patients with MTHFR deficiency require long\u2010term oral folate and betaine supplements. Long\u2010term oral methionine therapy should also be considered. Early treatment may lead to a favorable outcome with developmental recovery and prevention of further neurological deterioration. In contrast, most late\u2010treated patients have severe and irreversible neuromotor impairments. Hematological abnormalities are easily corrected.<\/jats:p>","DOI":"10.1007\/s10545-010-9120-8","type":"journal-article","created":{"date-parts":[[2010,5,20]],"date-time":"2010-05-20T07:39:47Z","timestamp":1274341187000},"page":"137-145","source":"Crossref","is-referenced-by-count":66,"title":["Isolated remethylation disorders: do our treatments benefit patients?"],"prefix":"10.1002","volume":"34","author":[{"given":"Manuel","family":"Schiff","sequence":"first","affiliation":[{"name":"Reference Center for Metabolic Disease Robert Debr\u00e9 University Hospital, APHP Paris France"},{"name":"Pediatric Neurology &amp; Metabolic disease Robert Debr\u00e9 University Hospital, APHP Paris France"},{"name":"Service de Neurop\u00e9diatrie &amp; Maladies M\u00e9taboliques, Centre de R\u00e9f\u00e9rence Maladies M\u00e9taboliques H\u00f4pital Robert Debr\u00e9 48, Boulevard S\u00e9rurier Paris 75019 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