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

A diagnosis of infantile Pompe's disease (glycogenosis type II) was made by muscle biopsy on a 6-month-old infant boy seen with hypotonia, weakness, and developmental regression. Histochemistry and electron microscopy revealed a vacuolar myopathy with massive glycoge accumulation associated with increased neutral lipid as demonstrated on Oil Red O reactions. Pleomorphic, hypertrophic mitochondria with distortion of cristae and electron-dense deposits within the matrix were identified. Acid alpha-1,4-glucosidase activity was absent but associated with increased neutral maltase activity and a variable compensatory rise in activity of other lysosomal enzymes. Biochemical studies demonstrated low free carnitine, normal acylcarnitine, increased activity of carnitine palmityl and acyl transferases, and other enzymes of beta-oxidation with the notable exception of low normal beta-hydroxyacyl-CoA dehydrogenase activity. The explanation for the lipid accumulation is uncertain but is likely related to the combination of low carnitine concentration in muscle, low beta-hydroxyacyl CoA dehydrogenase, representing a rate limiting enzyme of beta-oxidation, and nonspecific defective mitochondrial function.
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PMID:Infantile Pompe's disease, lipid storage, and partial carnitine deficiency. 187 Jun 35

Long-chain 3-hydroxyacyl-coenzyme A (CoA) dehydrogenase is one of three enzyme activities of the mitochondrial trifunctional protein. We report the clinical findings of 13 patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. At presentation the patients had had hypoglycemia, cardiomyopathy, muscle hypotonia, and hepatomegaly during the first 2 years of life. Seven patients had recurrent metabolic crises, and six patients had a steadily progressive course. Two patients had cholestatic liver disease, which is uncommon in beta-oxidation defects. One patient had peripheral neuropathy, and six patients had retinopathy with focal pigmentary aggregations or retinal hypopigmentation. All patients were homozygous for the common mutation G1528C. However, the enoyl-CoA hydratase and 3-ketoacyl-CoA thiolase activities of the mitochondrial trifunctional protein were variably decreased in skin fibroblasts. Dicarboxylic aciduria was detected in 9 of 10 patients, and most patients had lactic acidosis, increased serum creatine kinase activities, and low serum carnitine concentration. Neuroradiologically there was bilateral periventricular or focal cortical lesions in three patients, and brain atrophy in one. Only one patient, who has had dietary treatment for 9 years, is alive at the age of 14 years; all others died before they were 2 years of age. Recognition of the clinical features of long-chain 3-hydroxyacyl-CoA deficiency is important for the early institution of dietary management, which may alter the otherwise invariably poor prognosis.
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PMID:Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency with the G1528C mutation: clinical presentation of thirteen patients. 942 8

We report the premortem and postmortem morphologic and histologic features and biochemical findings of a patient with long-chain 3-hydroxyacyl-CoA dehydrogenase (L-CHAD) deficiency and compare these with those described in previously reported cases of L-CHAD deficiency. In addition to chronic nonketotic hypoglycemia, hypotonia, and liver failure, this patient had chronic hemolytic anemia and delayed central nervous system myelination. These features have not been previously documented in L-CHAD deficiency.
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PMID:Clinical, biochemical, and morphologic investigations of a case of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. 924 Sep 10

Deficiency of enoyl-CoA hydratase: 3-hydroxyacyl-CoA dehydrogenase (peroxisomal bifunctional enzyme), one of the enzymes of the peroxisomal beta-oxidation system, leads to clinical manifestations resembling Zellweger syndrome with hypotonia, psychomotor delay, hepatomegaly, typical facial appearance and accumulation of very long-chain fatty acids. The nucleotide sequence of the human peroxisomal enoyl-CoA hydratase: 3-hydroxyacyl-CoA dehydrogenase cDNA has been reported by Hoefler and colleagues; however, we have found some amino acid differences from our originally isolated cDNA. Contrary to the findings described in a previous paper, we report here the cDNA sequence of human peroxisomal enoyl-CoA hydratase: 3-hydroxyacyl-CoA dehydrogenase in which there are 9 authenticated amino acid alterations.
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PMID:Amino acid and nucleotide sequences of human peroxisomal enoyl-CoA hydratase: 3-hydroxyacyl-CoA dehydrogenase cDNA. 950 Dec 66

Current dietary management of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD; long-chain-(S)-3-hydroxyacyl-CoA:NAD+ oxido-reductase, EC 1.1.1.211) deficiency (LCHADD) is based on avoiding fasting, and minimizing energy production from long-chain fatty acids. We report the effects of various dietary manipulations on plasma and urinary laboratory values in a child with LCHADD. In our patient, a diet restricted to 9% of total energy from long-chain fatty acids and administration of 1.5 g medium-chain triglyceride oil per kg body weight normalized plasma acylcarnitine and lactate levels, but dicarboxylic acid excretion remained approximately ten times normal. Plasma docosahexaenoic acid (DHA, 22:6n-3) was consistently low over a 2-year period; DHA deficiency may be related to the development of pigmentary retinopathy seen in this patient population. We also conducted a survey of metabolic physicians who treat children with LCHADD to determine current dietary interventions employed and the effects of these interventions on symptoms of this disease. Survey results indicate that a diet low in long-chain fatty acids, supplemented with medium-chain triclyceride oil, decreased the incidence of hypoketotic hypoglycaemia, and improved hypotonia, hepatomegaly, cardiomyopathy, and lactic acidosis. However, dietary treatment did not appear to effect peripheral neuropathy, pigmentary retinopathy or myoglobinuria.
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PMID:Dietary management of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD). A case report and survey. 1023 7

The disorders of peroxisomal beta-oxidation, which have been well characterised at the molecular level, include defects of acyl-CoA oxidase, defects of the D-bifunctional protein (D-BP) (including specific defects of its enoyl-CoA hydratase and D-3-hydroxyacyl-CoA dehydrogenase components), defects of the very-long-chain fatty acid (VLCFA)-CoA importer [X-linked adrenoleukodystrophy (ALD)] and alpha-methylacyl-CoA racemase deficiency. A survey of the clinical consequences of these defects indicates that defects in the acyl-CoA oxidase and D-BP can produce neonatal hypotonia, seizures in early infancy, retinopathy and progressive neurological dysfunction with leukodystrophy on imaging. Defects in the VLCFA-CoA importer and in the racemase do not produce disease until a long time after the neonatal period. However, again the clinical picture is dominated by neurological disease: impaired cognitive function with leukodystrophy in childhood X-linked ALD and retinopathy and neuropathy in racemase deficiency. It is difficult to escape the conclusion that defective peroxisomal beta-oxidation has effects (such as impaired neuronal migration in the developing brain), which are more serious than those produced by the accumulation of substrates (VLCFAs, pristanic acid) alone.
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PMID:Clinical consequences of defects in peroxisomal beta-oxidation. 1135 71

Patients with long-chain 3-hydroxyacyl coenzyme A dehydrogenase (LCHAD) deficiency manifest hypoketotic hypoglycemia, hepatomegaly, hypotonia, lactic acidemia, acute renal failure, cardiomyopathy, and sudden death. We describe four novel mutations of the alpha- and beta-subunits of the mitochondrial trifunctional protein in four patients from three unrelated families. Their plasma acylcarnitine profiles suggested the presence of LCHAD deficiency by demonstrating highly elevated 3-hydroxyacyl carnitines by tandem mass spectrometry (MS/MS). Patients 1 and 2 had siblings who had died of lactic acidemia during the neonatal period. These patients also manifested lactic acidemia and died in the neonatal period. Patient 3 had a family history of Reye-like syndrome. She exhibited acute renal failure, rhabdomyolysis, pericardial effusion, and myopathy at the age of 12 years. DNA analysis of patients 1 and 2 revealed homozygosity for a c.1689+2T>G mutation of the HADHA gene, resulting in the skipping of exon 16 with an in-frame 69-bp deletion. Patient 3 was a compound heterozygosity of the HADHB gene, N307D/N389D. Patient 4, a 25-month-old baby, manifested recurrent episodes of lethargy, metabolic acidosis, elevated liver enzymes, and dark urine from the age of 10 months. Mutation analysis of the HADHB gene of patient 4 identified compound heterozygosity of N114D/N307D.
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PMID:Identification of novel mutations of the HADHA and HADHB genes in patients with mitochondrial trifunctional protein deficiency. 1714 51