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)

A patient with severe pyruvate carboxylase deficiency presented at age 11 weeks with metabolic decompensation after routine immunization. She was comatose, had severe lactic acidemia (22 mM) and ketosis, low aspartate and glutamate, elevated citrulline and proline, and mild hyperammonemia. Head magnetic resonance imaging showed subdural hematomas and mild generalized brain atrophy. Biotin-unresponsive pyruvate carboxylase deficiency was diagnosed. To provide oxaloacetate, she was treated with high-dose citrate (7.5 mol/kg(-1)/day(-1)), aspartate (10 mmol/kg(-1)/day(-1)), and continuous drip feeding. Lactate and ketones diminished dramatically, and plasma amino acids normalized, except for arginine, which required supplementation. In the cerebrospinal fluid (CSF), glutamine remained low and lysine elevated, showing the treatment had not normalized brain chemistry. Metabolic decompensations, triggered by infections or fasting, diminished after the first year. They were characterized by severe lactic and ketoacidosis, hypernatremia, and a tendency to hypoglycemia. At age 3(1/2) years she has profound mental retardation, spasticity, and grand mal and myoclonic seizures only partially controlled by anticonvulsants. The new treatment regimen has helped maintain metabolic control, but the neurological outcome is still poor.
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PMID:Treatment of pyruvate carboxylase deficiency with high doses of citrate and aspartate. 1058 40

GLUT1 deficiency syndrome (GLUT1DS, OMIM 606777) is a treatable epileptic encephalopathy resulting from impaired glucose transport into the brain. The essential biochemical finding is a low glucose concentration in the cerebrospinal fluid (CSF; hypoglycorrhachia; mean 1.7 [SD 0.3mmol/L]) in the setting of normoglycaemia. CSF lactate is normal. Patients present with an early-onset epilepsy resistant to anticonvulsants, developmental delay, and a complex movement disorder. Hypotonic, ataxic, and dystonic features are most prominent. Speech is often severely affected. Some patients develop spasticity and secondary microcephaly. The phenotype is highly variable ranging from severe impairment to children without seizures. Electroencephalography (EEG) may show 2.5-4Hz spike-waves improving on food intake. Neuroimaging is uninformative. Most patients carry heterozygous de novo mutations in the GLUT1 gene (OMIM 138140, gene map locus 1p35-31.3). Autosomal dominant transmission and several mutational hot spots have been identified, but phenotype-genotype correlations are not yet apparent. Homozygous GLUT1 mutations presumably are lethal. The ketogenic diet is the treatment of choice as it provides an alternative fuel to the brain. It should be introduced early and maintained into puberty. Seizures are effectively controlled with the onset of ketosis, but might recur and require comedication. The effect on neurodevelopment appears less impressive. The increasing number of patients, molecular and biochemical analysis, recent research into ketogenic diet mechanisms, and the development of animal models for GLUT1DS have brought substantial insights in disease manifestations and mechanisms. This review summarizes data on 84 published cases and highlights recent advances in understanding this entity.
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PMID:GLUT1 deficiency syndrome--2007 update. 1771 30