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 infants with lethargy, vomiting, convulsions, coma and marked metabolic acidosis were found to have very high concentrations of methylmalonic acid in their serum and urine. In vitro studies of fibroblasts demonstrated that the infants had different variants of methylmalonic acidemia.Vitamin B(12) was given in two different forms at 1 month of age and at 12 months of age. Each trial continued for 4 months but neither infant showed a clinical or biochemical response.In both infants hyperglycinemia, neutropenia and thrombocytopenia developed during acute metabolic crises only. Hypoglycemia was found in patient 2. Hyperammonemia was severe in patient 2 during acute crises but never appeared in patient 1. When clinically well, both infants continued to excrete abnormal amounts of methylmalonic acid in the urine and both had persistent compensated metabolic acidosis.Marked hyperuricemia developed in patient 1 at 18 months of age and led to progressive renal failure. Allopurinol therapy was necessary to keep the uric acid concentration within the normal range. Renal function returned to normal, as indicated by a marked increase in the renal clearance of creatinine and uric acid.Patient 1 is physically and mentally retarded, and has moderate hypotonia, hepatomegaly and persistent vomiting. Patient 2 has developed normally.The urine concentrations of methylmalonic acid in the four parents were normal.
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PMID:Methylmalonic acidemia: 6 years' clinical experience with two variants unresponsive to vitamin B12 therapy. 3 17

4 cases of nonketotic hyperglycinemia (glycine encephalopathy), one with autopsy, are presented and the literature on 61 cases is reviewed. Major clinical signs include early hypotonia, lethargy and erratic and massive myoclonias with respiratory distrubances, starting during the first days of life after a symptom-free interval. Early death is common. Survivors are severely retarded and exhibit various types of seizures including infantile spasms. The EEG pattern consists initially of periodical paroxysmal bursts on an almost flat tracing, evolving later into a hypsarrhythmic pattern. Spongiosis of the myelinated pathways is the main pathological finding. Elevated CSF glycine seems to be the essential determinant of the neurological disturbances and it is, therefore, suggested that the term glycine encephalopathy be used instead of non-ketotic hyperglycinemia. A classification of disorders associated with hyperglycinemia is proposed.
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PMID:Glycine encephalopathy. 58 64

A female infant with neonatal hypotonia and lethargy was found to have nonketotic hyperglycinemia. She died at the age of 5 days. Autopsy revealed slightly retarded myelination and severe spongy change in the well-myelinated areas of the brain. Analysis of this and the other 26 reported cases suggests that patients with nonketotic hyperglycinemia develop severe mental retardation, not seen in ketotic hyperglycinemia. Elevated glycine levels in the brain and cerebrospinal fluid appear to differentiate these two forms of hyperglycinemia better than the presence of ketosis or leukopenia, and high glycine levels apparently occur in the same areas as the spongy change. While both forms show defective glycine cleavage in the liver, defective glycine cleavage in the brain has been reported only in nonketotic hyperglycinemia.
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PMID:Nonketotic hyperglycinemia: report of a case and review of the clinical, chemical, and pathological changes. 61 56

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 6-month-old girl was hospitalized on three occasions for irritability, vomiting, acidosis, and hypotonia. During the third hospitalization hyperglycinemia and urinary glycolic acid were detected. Ethylene glycol was discovered in the infant's blood and bottled formula. Clinicians must consider ethylene glycol intoxication as a cause of recurrent infantile metabolic acidosis.
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PMID:Intentional infantile ethylene glycol poisoning presenting as an inherited metabolic disorder. 153 89

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

Nonketotic hyperglycinemia (NKH) is an inborn error of glycine degradation causing muscular hypotonia, seizures, apnea, and lethargy; it has a poor prognosis. Accumulation of glycine in the brain is thought to cause excessive stimulation of the N-methyl-D-aspartate receptor. Dextromethorphan (DM), an N-methyl-D-aspartate receptor antagonist, in doses of 5 to 35 mg/kg per day has been shown to have beneficial therapeutic effects in some patients with NKH. We report the case of a 1-year-old infant with NKH, seizure disorder, and psychomotor delay who was clinically seizure free during treatment with sodium benzoate, arginine, benzodiazepam, and phenobarbital. Although sodium benzoate normalized serum glycine levels (103 to 125 mumol/L), cerebrospinal fluid glycine levels remained elevated (42 to 47 mumol/L), with epileptiform activity on electroencephalography. The addition of low-dose DM (0.25 mg/kg per day) to the treatment led to improvement of electroencephalographic activity, resolution of nystagmus with increased eye contact, and modest progression of developmental milestones. These data suggest that DM at doses significantly lower than previously reported may be beneficial in some patients with NKH. Treatment with low-dose DM needs further evaluation.
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PMID:Efficacy of low-dose dextromethorphan in the treatment of nonketotic hyperglycinemia. 865 42

Glycine is a nonessential amino acid that serves as both an inhibitory and an excitatory neurotransmitter. Hyperglycinaemia occurs in non-ketotic hyperglycinaemia, a primary defect in the glycine cleavage pathway, and as a secondary feature of several inborn errors of organic acid metabolism. However, specifically low levels of glycine have never been reported. Here we report a child with complementation group C xeroderma pigmentosum (XP) characterized by a splice donor mutation in the XPC gene, multiple skin cancers and specific and persistent hypoglycinaemia. He has cognitive delay, lack of speech, autistic features, hyperactivity and hypotonia, all unexplained by the diagnosis of XP group C, a non-neurological form of the disease. Treatment with oral glycine has improved his hyperactivity. Specific hypoglycinaemia could indicate a metabolic disorder producing neurological dysfunction. Whether it is related to or coincidental with the XP is unclear.
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PMID:Hypoglycinaemia and psychomotor delay in a child with xeroderma pigmentosum. 1060 43

Methylmalonic acidemia (MMA) is an inborn error of organic acid metabolism that occurs in infancy with hypotonia, vomiting, dehydration, lethargy and failure to thrive and is biochemically characterized by metabolic ketoacidosis, hyperammonemia and sometimes hyperglycinemia. It results from deficiency of methylmalonyl-CoA mutase activity due to a defect in the mutase apoenzyme or to deficient function of one of the enzymes required for metabolism of its cofactor vitamin B12. Tubulointerstitial nephritis with progressive impairment of renal function is one of the most frequent long-term complications. We describe a case of a 17-year-old girl with methylmalonic acidemia unresponsive to vitamin B12 therapy. The clinical symptoms appeared at 4 months of life. She progressed into end stage renal disease and in January 1996 she started on hemodialytic treatment. In November 1996 we performed a kidney transplant. At present, urinary excretion of methylmalonic acid is normal and the renal function of the transplanted kidney is normal without any rejection episodes. We think that a kidney transplant could be a good therapeutic choice for the metabolic alterations in MMA with end stage renal disease. Indeed it would seem that the small methylmalonyl-CoA mutase activity present in the transplanted kidney could be sufficient to ensure normal metabolism of organic acids. Otherwise, the therapeutic goal can be achieved with a protein-restricted diet.
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PMID:Kidney transplantation in a girl with methylmalonic acidemia and end stage renal failure. 1168 86

Three unrelated adult patients with mild hyperglycinemia, infantile hypotonia, mental retardation, behavioral hyperirritability, and aggressive outbursts were screened for glycine decarboxylase (GLDC) mutations; two novel missense mutations (A389V and R739H) were found. Both mutations had a 6 to 8% of normal GLDC activities when expressed in COS7 cells.
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PMID:Glycine decarboxylase mutations: a distinctive phenotype of nonketotic hyperglycinemia in adults. 1582 56


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