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)

Congenital methylmalonic aciduria (MMA) is a metabolic disorder inherited by an autosomal recessive trait. The metabolic block is located in the catabolic pathway of propionyl-CoA to succinyl-CoA. Biochemically, four enzymatic defects have been recognized, i.e.: 1. Methylmalonyl-CoA racemase. 2. Methylmalonyl-CoA mutase apoenzyme. 3. Synthesis of desoxyadenosyl-cobalamine. 4. Disturbance at an earlier level of cobalamine metabolism which causes defective synthesis of both vitamin B12-coenzymes. These four enzymatic defects express themselves in three ways: non-vitamin B12-dependent MMA (defects 1 and 2); vitamin B12-dependent MMA (defect 3); MMA associated with homocystinuria (defect 4). The various forms of MMA cannot be distinguished clinically from one another. The disorder manifests itself during the first few days to weeks of life. Principal symptoms and signs are: anorexia, vomiting, muscular hypotonia and metabolic acidosis. The diagnosis is established by determination of methylmalonic acid in plasma, cerebrospinal fluid and urine, as well as by assay of enzyme activities in leukocytes, liver tissue or cultured fibroblasts (from biopsied skin). A prenatal diagnosis is feasible by the examination of cultured amnion cells, amniotic fluid and maternal urine. Therapy of non vitamin B12-dependent MMA calls for reduction of protein intake, particularly that of precursors of methylmalonic acid, such as methionine, threonine, isoleucine and valine. The treatment of vitamin B12-dependent forms is accomplished by i.m. injection of high doses of vitamin B12. No definite statement can be made as yet with regard to long-term prognosis and normalcy of mental development in treated children.
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PMID:[Methylmalonic aciduria. Classification, diagnosis and therapy (author's transl)]. 31 93

A new case of propionic acidemia is presented, paying special attention to the early symptoms of this disease, such as increased drowsiness, muscular hypotonia, poor feeding, hypothermia, metabolic acidosis, ketonuria and vomiting. Investigation by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) revealed the excretion of fairly high amounts of 2-methyl-3-oxovaleric acid, a condensation product of two molecules of propionyl-CoA, as well as the known pathological metabolites such as propionic, 3-hydroxypropionic and methylcitric acids. Among the post mortem findings the histological studies of the liver were the most remarkable.
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PMID:Excretion of 2-methyl-3-oxovaleric acid in propionic acidemia. 66 27

Propionyl CoA carboxylase deficiency was found in a 7-month-old boy who presented with attacks of vomiting, anorexia, weight loss, weakness, and hypotonia. He failed to thrive and had generalized seizures. He had propionic acidemia and hyperglycinemia; these are the manifestations of the ketotic hyperglycinemia syndrome. However, ketonuria was not a consistent part of his clinical picture, and he had at least two episodes of acute overwhelming illness, the latter one fatal, in which ketones were never found in the urine. Large amounts of pyrrolidone carboxylic acid were found in body fluids.
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PMID:Hyperglycinemia and propionyl coA carboxylase deficiency and episodic severe illness without consistent ketosis. 113 51

A congestive cardiomyopathy was diagnosed in a girl at the age of 4 weeks. In the weeks following she developed general muscle hypotonia and plasma lactate increased to 8.5 mmol/L. Biochemical investigations of a muscle biopsy at the age of 3 months showed a deficiency in the oxidation of all substrates tested: pyruvate plus malate, 2-ketoglutarate and palmitate plus malate. After freezing and thawing of the homogenate and the addition of essential cofactors, the oxidation of the ketoacids normalized. The oxidation defect in the untreated homogenate can be explained by a deficiency in one of the cofactors (such as thiamine pyrophosphate, NAD+ or CoASH), or by a defect in the oxidative phosphorylation. Treatment with thiamine and carnitine resulted in a decrease in blood lactate to normal levels and a dramatic clinical improvement. Suspension of thiamine caused deterioration of her clinical condition and lactic acidaemia. The thiamine therapy was then continued. The girl is now 6 years old and in perfect health.
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PMID:Neonatal cardiomyopathy and lactic acidosis responsive to thiamine. 186 62

Propionic acidemia is a rare hereditary disease which is an autosomal recessive disorder. Defect of propionyl CoA carboxylase results in abnormal accumulation of propionate and its metabolites which interfere the pathway of glycine cleavage and the urea cycle. This organic acidemia is characterized by a wide spectrum of clinical and biochemical findings, including recurrent vomiting, difficult feeding, lethargy, hypotonia, metabolic ketoacidosis, hyperglycinemia and hyperammonemia during the acute episodes. We present a male newborn infant who sustained this disorder and was managed successfully with blood exchange transfusion, peritoneal dialysis, supplemented with sodium benzoate and sodium bicarbonate therapy. Urine gas chromatography disclosed significant elevation of propionate and its metabolites which subsided 2 days after peritoneal dialysis. Special designed formula was then given with restriction of protein intake and supplement with sodium benzoate and sodium carbonate. Prenatal genetic counseling is necessary in further pregnancy. Diagnosis can be obtained when propionyl CoA carboxylase activity is low in cultured amniotic fluid cells or chorion villi sample or when there is abnormally high methylcitrate level in amniotic fluid.
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PMID:[Propionic acidemia: report of a case that is successfully managed by peritoneal dialysis and sodium benzoate therapy]. 217 70

Secondary carnitine deficiency in a patient with glutaric acidaemia type II, due to deficient ETF-dehydrogenase activity, is described. The patient responded clinically to a pharmacological dose of riboflavin and a restricted protein diet. In the second year of her life she developed more frequent and severe exacerbations during intercurrent infections from which she did not fully recover. Hypotonia and marked ataxia persisted. Plasma carnitine was entirely complexed as acylcarnitine with no free carnitine detected. Retrospective evaluation of several frozen urine specimens obtained since the age of 10 months revealed undetectable free carnitine with elevated acylcarnitine levels. Marked clinical improvement was observed following L-carnitine supplementation. The hypotonia and ataxia disappeared. The frequency and the severity of the exacerbations were noticeably decreased. The role of L-carnitine in preventing the accumulation of acyl-CoA compounds in inborn errors of organic acid metabolism is further emphasized by this patient. The necessity to evaluate free carnitine, acylcarnitine and acyl/free ratio in the assessment, follow-up and management of patients with inborn errors of organic acid metabolism is discussed.
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PMID:The importance of recognizing secondary carnitine deficiency in organic acidaemias: case report in glutaric acidaemia type II. 246 19

A girl suffering from marked muscular hypotonia, severe statomotor and mental retardation, bilateral optic atrophy with chorioretinal degeneration, convulsions and a moderate compensated metabolic acidosis is described. Screening for metabolic disorders revealed massive 3-methylglutaconic with 3-methylglutaric aciduria leading to the tentative diagnosis of 3-methylglutaconyl-CoA hydratase deficiency. Metabolite excretion was correlated with variation of leucine intake. 3-methyl-3-hydroxyglutaryl-CoA lyase activity in cultured fibroblasts was normal. The suspected metabolic defect was not demonstrable in cultured skin fibroblasts, however.
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PMID:3-Methylglutaconic and 3-methylglutaric aciduria in a patient with suspected 3-methylglutaconyl-CoA hydratase deficiency. 258 Jul 10

A 4.5-year-old male patient is described with chorioretinopathy, minor facial anomalies, delayed closure of the fontanel, mental retardation, moderate hypotonia, epilepsy and hepatic fibrosis. Postural control, intentional vocalising and manual dexterity were superior to the performance of patients with classical Zellweger syndrome (ZS). Morphologically distinct peroxisomes were absent in the liver. In blood elevated pipecolic acid levels and abnormal levels of bile acid intermediates were found. The plasmalogen content of erythrocytes was normal. In fibroblasts we found an accumulation of very long chain fatty acids, decreased activity of acyl CoA:dihydroxyacetone phosphate acyltransferase, and impaired de novo biosynthesis of plasmalogens. On the basis of these clinical, ultrastructural and biochemical characteristics we assume that this patient represents a milder variant of the classical cerebro-hepato-renal syndrome of Zellweger.
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PMID:A milder variant of Zellweger syndrome. 407 50

Two patients presented in early childhood with: 1) alopecia, skin rashs, and candida dermatitis; 2) severe hypotonia, ataxia and motor retardation; 3) frequent episodes of ketoacidosis with hyperlactacidemia. Propionic and methylcrotonic aciduria only appeared on hyperprotidic diet. Mitochondrial biotin-dependent carboxylase activities were decreased in the liver and leukocytes, but were paradoxically normal in cultured fibroblasts whatever the biotin content of the medium. These disorders responded to biotin administration, pointing to multiple biotin-dependent carboxylase deficiencies (MCD). Our report stresses the polymorphism of MCD: major discrepancies concern predominance of carboxylase deficiency, expression of MCD in cultured fibroblasts, and possible involvement of a cytoplasmic biotin enzyme, acetyl CoA carboxylase (ACC). Finally, we suggest that MCD could be of two types: impaired biotin metabolism (absorption, transport, activation) might result in generalization MCD involving ACC. Defective holocarboxylase synthetase might lead to a pure mitochondrial MCD with fibroblastic deficiency and presumably skin integrity.
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PMID:[Multiple biotin-dependent carboxylase deficiencies (author's transl)]. 611 72

We studied two children who developed normally for the first 3-4 months of life and then displayed a failure-to-thrive syndrome, regression in psychomotor development, pronounced muscular hypotonia, and liver damage. At the age of about 1-2 years, optic atrophy and spastic parapareses were evident. One child died at the age of 2.5 years the other at an age of 4 years. Both children excreted 3-methylglutaconic acid, 0.1-0.4 mol/mol creatinine and 3-methylglutaric acid, 0.02-0.05 mol/mol creatinine. The excretion of 3-hydroxy-3-methylglutaric acid was not increased. One of the children was available for further biochemical studies. The activity of hydroxymethylglutaryl-CoA lyase (EC 4.1.3.4) was moderately reduced in leucocytes and fibroblasts. During a 21-h fast there was a normal formation of ketone bodies and we conclude that the cause of the syndrome is not a deficiency of hydroxymethylglutaryl-CoA lyase. Normal formation of 14CO2 from [1-14C]isovaleric acid and [2-14C]leucine in fibroblasts and leucocytes apparently excludes a deficiency of methylglutaconyl CoA-hydratase (EC 4.2.1.18).
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PMID:3-Methylglutaconic aciduria in two infants. 619 9


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