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)

A 3-year 8-month-old girl died after 14 months of illness characterized by episodes of intermittent ataxia associated with oculomotor palsy, hypotonia, mental confusion, and disturbances of consciousness. In the last 4 months of life, there were signs of liver dysfunction. Pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase activities were normal in autopsy brain specimens and in cultured fibroblasts from the patient. Carnitine acetyltransferase was deficient in liver, brain, kidney, and cultured fibroblasts. Medium- and long-chain carnitine acyltransferase activities were normal. It is proposed that a functional defect of acetyl-coenzyme A (acetyl-CoA) utilization in brain mitochondria accompanies the carnitine acetyltransferase deficiency.
 ...
PMID:Fatal ataxic encephalopathy and carnitine acetyltransferase deficiency: a functional defect of pyruvate oxidation? 57 20

We report an inborn error of the tricarboxylic acid cycle, alpha-ketoglutarate dehydrogenase deficiency, in three siblings with hypotonia, metabolic acidosis, and hyperlactatemia immediately after birth. Neurologic deterioration resulted in death at about 30 months of age. We propose low molar ratios of ketone bodies in plasma of neonates with congenital lactic acidosis as an indication of dysfunction of the tricarboxylic acid cycle.
 ...
PMID:Alpha-ketoglutarate dehydrogenase deficiency presenting as congenital lactic acidosis. 164 Feb 93

A 6-month-old girl with vomiting, hypotonia and motor retardation was found to have elevated blood lactate, pyruvate, and branched chain amino acids associated with ketoglutaric aciduria. The combination of a congenital lactic acidosis with a variant form of maple syrup urine disease and ketoglutaric aciduria suggested a defect of a single component, common to pyruvate dehydrogenase, to branched chain ketoacid dehydrogenase, and to alpha-ketoglutarate dehydrogenase. Dihydrolipoyl dehydrogenase is the common component (E3). The three enzyme activities and the E3 component activity were found to be reduced in liver and cultured fibroblasts, thus confirming that a single defect of this component can result in a multiple deficiency involving several oxidative decarboxylation reactions.
 ...
PMID:Congenital lactic acidosis, alpha-ketoglutaric aciduria and variant form of maple syrup urine disease due to a single enzyme defect: dihydrolipoyl dehydrogenase deficiency. 689 45

A 4.5-year-old boy with chronic progressive encephalopathy is described. The clinical presentation initially included seizures and hypotonia which later evolved into severe extrapyramidal disease and dementia. The gas chromatography/mass spectrometry (GC/MS) analysis of urine indicated that alpha-ketoglutarate was increased 210 times and aconitic acid 80 times. No disturbance of acid/base balance, lactic acid or ammonia metabolism accompanied this clinical picture. The fibroblasts contained 29% of normal alpha-ketoglutarate dehydrogenase activity, while the activity of another mitochondrial marker enzyme, glutamate dehydrogenase, was normal. The neuroimaging studies revealed bilateral striatal necrosis. The clinical and biochemical findings were almost identical to two previously reported patients. Experience with this patient emphasizes the need for detailed organic acid biochemical investigation in any progressive encephalopathy and that extrapyramidal tract signs should evoke the possibility of alpha-ketoglutaric aciduria, among other 'neurologic organic acidemias'.
 ...
PMID:A new patient with alpha-ketoglutaric aciduria and progressive extrapyramidal tract disease. 772 79

Two new familial cases of 2-ketoglutarate dehydrogenase (2-KGD) deficiency are reported: a girl who died at 10 years and a boy, still alive at 4 years, born to consanguineous parents. The cases developed progressively severe encephalopathy with axial hypotonia, psychotic behaviour, pyramidal symptoms and failure to thrive. Both children exhibited permanent lactic acidosis with acute episodes during emotional stress and various infections, associated with elevated lactate/pyruvate (L/P) ratio and slightly decreased ketone body ratio in plasma. In fibroblasts, the L/P ratio was greatly increased in the boy. No respiratory chain complex deficiency could be demonstrated in cultured fibroblasts or in mitochondria isolated from a muscle biopsy performed on the boy. In muscle isolated mitochondria, a progressive decrease of the rate of glutamate oxidation was observed after ADP addition; the rate of 2-ketoglutarate oxidation was low in the absence of ADP and did not increase after ADP addition. 2-KGD deficiency was demonstrated in fibroblasts from both children and in the boy's muscle and myoblasts. The 2-KGD complex is composed of three separate enzymes: E1, E2 and E3. We could demonstrate in our patient that the E1 and E3 subunits were normal, suggesting that the E2 component could be responsible for the defect.
 ...
PMID:2-Ketoglutarate dehydrogenase deficiency, a rare cause of primary hyperlactataemia: report of a new case. 829 96

Canavan disease (CD) is an autosomal recessive disorder caused by aspartoacylase deficiency leading to accumulation of N-acetylaspartic acid and spongy degeneration of the brain. The mouse model for CD showed low levels of glutamate and gamma-aminobutyric acid (GABA) in the brain. Whether the low levels of glutamate and GABA observed in the CD mouse brain lead to abnormal production of glutamate-GABA associated enzymes and resulting succinate production is not obvious. While glutamate dehydrogenase and alpha-ketoglutarate dehydrogenase complex activities are lower in the cerebellum and brain stem of the CD mouse, alanine aminotransferase and succinate semialdehyde dehydrogenase (SSADH) activities and succinate level are similar to the levels observed in the wild type. Deficiency of SSADH has been suggested to be associated with mental retardation and hypotonia, similar to the clinical features of CD. The normal SSADH activity in the CD mouse brain suggests that mental retardation and hypotonia seen in the CD mouse is not due to SSADH activity and if documented also in patients with CD.
 ...
PMID:Mental retardation and hypotonia seen in the knock out mouse for Canavan disease is not due to succinate semialdehyde dehydrogenase deficiency. 1501 27