Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We reviewed 153 episodes of cobalamin deficiency involving the nervous system that occurred in 143 patients seen over a recent 17-year period at 2 New York City hospitals. Pernicious anemia was the most common underlying cause of the deficiency. Neurologic complaints, most commonly paresthesias or ataxia, were the first symptoms of Cbl deficiency in most episodes. The median duration of symptoms before diagnosis and treatment with vitamin B12 was 4 months, although long delays in diagnosis occurred in some patients. Diminished vibratory sensation and proprioception in the lower extremities were the most common objective findings. A wide variety of neurologic symptoms and signs were encountered, however, including ataxia, loss of cutaneous sensation, muscle weakness, diminished or hyperactive reflexes, spasticity, urinary or fecal incontinence, orthostatic hypotension, loss of vision, dementia, psychoses, and disturbances of mood. Multiple neurologic syndromes were often seen in a single patient. In 42 (27.4%) of the 153 episodes, the hematocrit was normal, and in 31 (23.0%), the mean corpuscular volume was normal. Neutropenia and thrombocytopenia were unusual even in anemic patients. In nonanemic patients in whom diagnosis was delayed, neurologic progression frequently occurred although the hematocrit remained normal. In 27 episodes, the serum cobalamin concentration was only moderately decreased (in the range of 100-200 pg/ml) and in 2 the serum level was normal. Neurologic impairment, as assessed by a quantitative severity score, was judged to be mild in 99 episodes, moderate in 39 and severe in 15. Severity of neurologic dysfunction before treatment was clearly related to the duration of symptoms prior to diagnosis. In addition, the hematocrit correlated significantly with severity, independent of the longer duration of symptoms in nonanemic patients. Four patients experienced transient neurologic exacerbations soon after beginning treatment with cyanocobalamin, with subsequent recovery. Followup evaluation was adequate to assess the neurologic response to vitamin B12 therapy in 121 episodes. All patients responded, and in 57 (47.1%), recovery was complete, with no remaining symptoms or findings on examination. The severity score was reduced by 50% or greater after treatment in 91% of the episodes. Residual long-term moderate or severe neurologic disability was noted following only 7 (6.3%) episodes. The extent of neurologic involvement after treatment was strongly related to that before therapy as well as to the duration of symptoms. The percent improvement over baseline neurologic status after treatment was inversely related to duration of symptoms and hematocrit. Some evidence of response was always seen during the first 3 months of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neurologic aspects of cobalamin deficiency. 164 56

We describe two patients with methylmalonic aciduria and homocystinuria (Cbl C). The disorder was not diagnosed in patient 1 until 4 1/2 years of age; he had a history of fatigue, anorexia, delirium, and spasticity. Moderate megaloblastic bone marrow changes were observed, and there was hyperreflexia of the lower limbs. His condition improved clinically with hydroxycobalamin therapy. Patient 2 was hospitalized at 6 weeks of age because of lethargy and poor feeding. She was found to have macrocytosis. Despite an initial good clinical response to hydroxycobalamin, she developed a striking pigmentary retinopathy. Methylmalonic aciduria persisted in both patients, and homocystinuria persisted in patient 1 despite therapy. The diagnosis of Cbl C disease has been confirmed in both patients by biochemical studies of cultured fibroblasts, including complementation studies. The differences in age of onset and clinical findings together with the similar biochemical findings in these two patients demonstrate the heterogeneity of phenotypic expression in patients with apparently identical abnormalities of vitamin B12 metabolism.
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PMID:Clinical heterogeneity in cobalamin C variant of combined homocystinuria and methylmalonic aciduria. 395 Aug 20