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)

Two siblings with consanguineous parents began having myoclonic jerks at age 5 months after introduction of mixed feeding. There was later developmental regression. The elder girl died without diagnosis aged 1 year, after prolonged continuous hyperventilation. The younger sibling did not have metabolic acidosis when first investigated for myoclonus and hypotonia aged 5 months. At 9.5 months, when intermittently decerebrate and hyperventilating, she had a metabolic acidosis with elevated blood lactic, pyruvic and beta-hydroxybutyric acids, and beta-hydroxyisovaleric aciduria. On the assumption that she had beta-methylcrotonyl-CoA carboxylase deficiency she was started on biotin, 10 mg daily. Within 36 h there was dramatic clinical and biochemical improvement. Previously defective eye movement control and gaze became normal, hyperventilation ceased, and excessive organic acid excretion in urine was abolished. She remains on long-term biotin and at age 2 years her development appears normal in all respects. Fibroblast culture however revealed normal quantities of the enzymes beta-methylcrotonyl-CoA carboxylase, propionyl-CoA carboxylase and pyruvate carboxylase. Irrespective of niceties of enzyme and organic acid biochemistry, the clinician must be aware of biotin-reversible regressive brain disease which may present before manifest metabolic acidosis.
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PMID:Biotin-reversible neurodegenerative disease in infancy. 308 40

The files of 25 patients with propionic acidemia (PA), followed by the Inborn Errors of Metabolism Service (IEMS) at King Faisal Specialist Hospital and Research Centre (KFSH & RC) from 1990 to 1993, were studied retrospectively. In 14 patients PA presented acutely with acidosis, hyperammonemia and thrombocytopenia, while in 11 patients the presentation of the disease was unusual. In the latter group, two neonates with PA initially appeared as a primarily hyperammonemic metabolic disease. In two other neonates the vomiting was so severe that they were diagnosed as intestinal obstruction in referral hospitals. The presentation in three infants was primarily as an immune disorder. In four infants, PA appeared as an acute or chronic encephalopathy, i.e. as a silent organic acidemia, with few other findings of the disease. The clinical picture of PA includes facial and nipple dysmorphia, severe hypotonia and vomiting. Severe thrombocytopenia is the hallmark of the metabolic crisis. In one patient it was noticed late and caused intracranial hemorrhage, while in three others intracranial bleeding caused death. The prognosis in PA remained grave despite rigorous treatment. Only seven of the 25 PA patients remained to have a normal life-style, while eight patients expired. The diagnosis is readily achieved by urine gas chromatography/mass spectrometry (GC/MS), by tandem mass spectrometry (MS/MS), or by enzyme analysis of fibroblasts. While there may be both examiner- and patient-related reasons for the variations in the presentation of PA, one other reason may be the heterogeneity of the molecular defect in propionyl-CoA carboxylase.
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PMID:Unusual presentations of propionic acidemia. 772 81

Comprehensive data on 30 patients with propionic acidaemia, diagnosed by selective screening for inborn errors of metabolism, are presented. The most valuable diagnostic metabolites found were methylcitric-, 3-hydroxypropionic-, and 2-methyl-3-oxovaleric acids. Hyperlysinaemia and hyperlysinuria are also characteristic findings in this disease. The metabolic pattern found in propionic acidaemia is discussed extensively as are enzymatic findings. Residual activity of propionyl-CoA carboxylase is neither a predictive marker for severity nor for outcome of the disease. Propionate fixation assays were less reliable for confirmation of propionic acidaemia and of no prognostic value. Clinical presentation of the disease is discussed in detail. Besides the well-known unspecific findings (poor appetite, feeding difficulties, vomiting, dehydration, weight loss, muscular hypotonia, dyspnoea, somnolence, apathy, convulsion, coma, severe metabolic acidosis, hyperammonaemia) various skin abnormalities have been detected in about 50% of all patients. In 27% "dermatitis acidemica" was found.
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PMID:Propionic acidaemia: clinical, biochemical and therapeutic aspects. Experience in 30 patients. 795 90

Propionic acidemia is a hereditary metabolic disease caused by a deficiency of enzyme propionyl-CoA carboxylase, which is involved in the catabolism of ramified amino acids, odd-chain fatty acids, and other metabolites; the deficiency of this enzyme leads to an accumulation of toxic substances in the body. There are various forms of clinical presentation (severe neonatal, chronic intermittent, or slow and gradual). The case presented in this study was of a slow and insidious evolution form that was diagnosed when the child was 9 months old. Intracranial magnetic resonance imaging showed a slight increase in the signal intensity in sequences measured in T2 in addition to a restriction of the diffusion at the level of both putamens, which, together with biochemical and genetic analyses, confirmed the diagnosis of propionic acidemia. After initiating treatment involving a diet that was low in proteins, carnitine, and biotin, and an open-formula diet of ramified amino acids, the patient made progress, showing signs of improved hypotonia and increased weight gain. His vomiting stopped, and ketoacidosis was corrected.
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PMID:Subacute presentation of propionic acidemia. 1817 61

Propionic acidemia is an autosomal recessive disorder as a result of a deficient activity of propionyl-CoA carboxylase. Propionyl CoA is metabolized by propionyl-CoA carboxylase to methylmalonyl CoA. Propionic acidemia is a major cause of ketotic hyperglycinemia. This disorder is characterized by episodic vomiting, dehydratation, feeding intolerante, lethargy, hypotonia, metabolic acidosis, ketosis and hyperammonemia. The patient presented herein was a full-term female newborn with encephalopathy in the first days of life. She presented hypoglycemia, metabolic acidosis with increased anion gap, ketosis, hyperammonemia, anemia, leukopenia and thrombocytopenia. The brain ultrasonography was normal. The tandem mass expectrometry done by Pediatrix was abnormal, with the acylcarnitine results consistent with an organic acidemia. The parents are consanguineus and have a history of abortus, miscarriage and neonatal death, characteristics suggestive of the presence of genetic defects.
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PMID:[Neonatal onset of organic acidemia (propionic) diagnosed by tandem mass spectrometry]. 1864 57