Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two children are described who suffered from episodes of metabolic acidosis and progressive mental and motor deterioration. The patients showed periodic elevation of blood lactate, pyruvate and alanine, which was accompanied by vomiting, hypotonia or convulsions. The concentrations of lactate and pyruvate in cerebrospinal fluid were found to be increased. Liver biopsies revealed a decrease in pyruvate carboxylase activity and normal pyruvate decarboxylase activity. No inhibitor of TPP-ATP phosphoryl transferase was detected in urine from the patients. These findings suggest that congenital lactic acidosis due to pyruvate carboxylase deficiency is probably a different disease entity from Leigh's encephalomyelopathy. A possible mechanism of brain damage caused by a defect in pyruvate carboxylase is postulated.
 ...
PMID:Congenital lactic acidosis due to pyruvate carboxylase deficiency: absence of an inhibitor of TPP-ATP phosphoryl transferase. 20 66

An 11-month-old boy with muscle hypotonia and neurologic deteriorations had lactic acidosis, pyruvic acidemia and alaninemia due to deficiency of the pyruvate dehydrogenase complex in his platelets and of pyruvate decarboxylase in his muscle. When placed on a low carbohydrate-high fat diet for 6 months, his blood levels of lactate and pyruvate became nearly normal, but his cerebrospinal fluid levels of lactate and pyruvate remained high. Despite this dietary therapy, neurologic deterioration progressed slowly. He died of pneumonia after artificial respiration for 3 wk. At autopsy, extensive symmetric lesions were found in the brain including proliferation of capillaries and gliosis in the brain stem and diffuse demyelination in the white matter. These lesions were consistent with those observed in Leigh's disease. The activities of the pyruvate dehydrogenase complex and pyruvate decarboxylase in various tissues obtained at autopsy were less than 10% of control values; however, the activities of pyruvate carboxylase and alpha-ketoglutarate decarboxylase were within the normal limits. This patient with Leigh's disease had an isolated deficiency of pyruvate decarboxylase in various tissues.
 ...
PMID:Enzymologic studies and therapy of Leigh's disease associated with pyruvate decarboxylase deficiency. 709 58

A 23-month-old boy with progressive muscular hypotonia and mental and motor deterioration was described. Four days after the admission he had a respiratory arrest and required the care in a respirator thereafter. Laboratory examinations showed metabolic acidosis and high levels of pyruvate, lactate and alanine in blood and cerebrospinal fluid. Oral administration of thiamine-HCl and lipoic acid was noneffective and he died 7 months after the admission. Autopsy findings were compatible with subacute necrotizing encephalomyelopathy (Leigh's disease). The activity of pyruvate decarboxylase in autopsy samples was not detectable and that in fibroblasts was 9% of that in control cell lines. The present study confirmed that pyruvate decarboxylase deficiency is one of the causes of Leigh's disease.
 ...
PMID:Pyruvate decarboxylase deficiency in a patient with Leigh's encephalomyelopathy. 712 39

Pyruvate dehydrogenase deficiency is one of the most common causes of encephalopathy associated with lactic acidosis and is known to account for congenital lactic acidosis, recurrent ataxia, and infantile Leigh syndrome. Hitherto, however, peripheral neuropathy has not been regarded as a presenting symptom of pyruvate dehydrogenase deficiency. Here, we report on a boy who presented peripheral neuropathy with severe limb hypotonia, absent deep-tendon reflexes, and reduced motor nerve conduction velocities at 8 months of age. Persistent hyperpyruvicemia with normal lactate/pyruvate molar ratios in plasma were highly suggestive of a pyruvate dehydrogenase deficiency, and the determination of pyruvate dehydrogenase activity in circulating lymphocytes led to the diagnosis of pyruvate decarboxylase (PDH-E1) deficiency in the proband. Based on this observation, we suggest that pyruvate dehydrogenase deficiency should be considered in the diagnosis of peripheral neuropathy in infancy, especially when associated with persistent hyperpyruvicemia, normal lactate/pyruvate molar ratios in plasma, and recurrent episodes of drowsiness and hypotonia of unknown origin.
 ...
PMID:Leigh syndrome: pyruvate dehydrogenase defect. A case with peripheral neuropathy. 815 Oct 84