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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Non-ketotic hyperglycinaemia was diagnosed in a newborn infant presenting with lethargy, apnoea, hiccoughs and myoclonic seizures. The typical findings of raised cerebrospinal fluid:plasma glycine ratio, a burst suppression pattern on electro-encephalography, hypodense areas seen on computed tomography and lack of acidosis, ketosis and serum organic acid abnormality confirmed the diagnosis. Prenatal diagnosis by investigating the glycine cleavage enzyme system from a chorionic villus sample is not yet available.
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PMID:Non-ketotic hyperglycinaemia in a neonate. A case report. 187 59

Symptomatic hypoglycemia developed 5 to 45 months after transplantation in nine children who had renal transplants before 6 years of age. During hypoglycemia, serum glucose levels ranged from 14 to 39 mg/dl (0.8 to 2.1 mmol/L). Hypoglycemic episodes occurred between 1.7 and 7.5 years of age. Six patients had generalized seizures; the remaining three had diaphoresis with stupor or lethargy. None of the children had serious infections, diabetes, congenital defects of glucose metabolism, or a history of treatment with insulin or oral hypoglycemic agents. Six patients had hypoglycemic symptoms after a prolonged fast, and at least four had ketosis. Eight of the nine patients were receiving propranolol when hypoglycemia occurred. No differences in the daily prednisone dose, the number of transplant rejection episodes, or the frequency of treatment with medications other than propranolol were noted between hypoglycemic patients and 56 normoglycemic age-matched renal transplant recipients. All hypoglycemic patients were subsequently treated with frequent feedings and discontinuation of propranolol. No further hypoglycemic episodes have occurred in eight of nine patients. Symptomatic hypoglycemia should be recognized as a potentially devastating complication of pediatric renal transplantation.
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PMID:Hypoglycemia in pediatric renal allograft recipients. 305 55

3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMG-CoA lyase) is an inborn error of leucine catabolism which often leads to life-threatening illness in the neonatal period. The cardinal clinical features include severe infantile hypoglycemia, metabolic acidosis, hepatomegaly, lethargy or coma and apnea. Hyperammonemia is variable. There is a characteristic absence of ketosis. Considerable heterogeneity has been observed in clinical and biochemical presentation. Acute episodes of illness have been mistaken for Reye syndrome. The pattern of organic acids in the urine includes large amounts of 3-hydroxy-3-methylglutaric, 3-methyl-glutaconic, 3-methylglutaric and 3-hydroxyisovaleric acids. Smaller, but appreciable levels of glutaric, adipic and other dicarboxylic acids may also be excreted in the urine. Lactic acid may be present in sizable amounts at times of acute illness. The primary defect is a deficiency of 3-hydroxy-3-methylglutaryl-coenzyme A lyase, a key enzyme in the cycle of ketogenesis.
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PMID:3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: review of 18 reported patients. 306 29

Two adolescent boys with Kearns-Sayre syndrome (progressive external ophthalmoplegia, heart block, elevated CSF protein, and ragged-red muscle fibers) developed lethargy, increasing somnolence, polydipsia, polyphagia, and polyuria after a brief course of steroid therapy. Both had hyperglycemia and acidosis. Nonketotic, lactic acidosis was present in one and ketosis in the other. Severe respiratory failure developed, and both patients died. Postmortem revealed fatty infiltration of the pancreas in addition to a diffuse spongiform encephalopathy.
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PMID:Fatal metabolic acidosis, hyperglycemia, and coma after steroid therapy for Kearns-Sayre syndrome. 370 1

This paper presents the clinical and metabolic findings in two young boys with long-standing Kearns-Sayre syndrome. Following short exposure to oral prednisone, both boys developed lethargy, increasing somnolence, polydipsia, polyphagia, and polyuria. Both presented in the emergency room with profound coma, hypotension, severe hyperglycemia, and acidosis. Nonketotic lactic acidosis was present in one and ketosis without a known serum lactate level was present in the other. Respiratory failure rapidly ensued and both patients expired in spite of efforts at resuscitation. We believe these two cases represent a newly described and catastrophic metabolic-endocrine failure in the Kearns-Sayre syndrome.
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PMID:Hyperglycemic acidotic coma and death in Kearns-Sayre syndrome. 370 9

Organic acidurias are congenital errors of the intermediate metabolism caused by a specific metabolic defect which gives rise to an anomalous excretion of carboxilic acids. The majority of these disease appear in the first weeks of life with few specific symptoms as hypotonia, lethargy, coma, seizures, vomits and dehydration. From biochemical point of view the findings of metabolic acidosis, ketosis, and hyperamoniemia are common. Frequently clinical symptoms are precipitated by infectious disease, traumatism or stress situations. The treatment applied in the initial phases may be efficient; for this reason diagnostic and early treatment are necessary for avoid irreversible sequelae. The diagnosis is also important for posterior genetic counseling. Organic acidurias are an interesting field of work for the pediatrician, neuropediatrician, biochemist and dietician to offer new perspectives in the diagnosis and treatment of many congenital errors of the metabolism.
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PMID:[Organic aciduria. Forms of presentation and treatment]. 372 91

By means of gas chromatographic methods substantial amounts of the C6-C10-dicarboxylic acids, i.e. adipic, suberic and sebacic acids, have been found in the urine from children with unexplained attacks of lethargy and hypotonia, presumably related to episodes of fever and/or insufficient food intake. The course have once been fatal and is often characterized by severe hypoglycemia without ketonuria. Systematic gas chromatographic/mass spectrometric determinations of selected organic acid metabolites in the urine, together with enzymatic measurements in fibroblasts and clinical data from 4 patients of this category, have shown that the biochemical basis of this syndrome can be inborn errors of the beta-oxidation of fatty acids, localized to the medium-chain acyl-CoA dehydrogenation system. The biosynthesis of adipic, suberic and sebacic acids was studied using ketotic rats as the model, since ketosis in rats and humans is accompanied by excessive urinary excretion of adipic and suberic acids. A probable pathway for the production of the three dicarboxylic acids was found to be an initial omega-oxidation of the medium-chain C10-C14-monocarboxylic acids followed by beta-oxidation of the resulting medium-chain dicarboxylic acids. It is argued that the source of the omega-oxidizable monocarboxylic acids in ketosis most probably is the fat deposites, and it is speculated that the patients with beta-oxidation defects supplement this source with beta-oxidation intermediate medium-chain monocarboxylic acids, accumulated as a result of the defect. The ratio between the excreted amounts of adipic acid and sebacic acid in the urine from the patients with beta-oxidation defects is less than 50. This is in contrast to the ratio in urine from ketotic patients, where it is greater than 100. Adipic acid/sebacic acid ratio-measured by means of a gas chromatographic analysis-is therefore suggested as a tool in the diagnosis of dicarboxylic acidurias. Based on the clinical picture and the pattern of a series of organic acids in the urinary metabolic profile our four patients can be divided in two types of dicarboxylic aciduria. The two types have different therapeutic implications.
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PMID:C6-C10-dicarboxylic aciduria: biochemical considerations in relation to diagnosis of beta-oxidation defects. 695 31

Goldberger discovered human pellagra was a non-infectious disease, affecting mostly the small and the timid in overcrowded institutions. Symptoms were diarrhoea, dermatitis and dementia. The staff and older children escaped the disease. They ate the meat and left the small and timid with the gravy. The 'Goldberger syndrome' is observed during competitive feeding of livestock, in ketotic animals and in the zinc depleted which are lethargic and pick all day at their feed. The pellagra preventative factor was later found to be nicotinic acid, derived from the amino acid tryptophan. Deficiencies of copper, magnesium, vitamin B6 (activated by a zinc kinase) inhibit the conversion of tryptophan to nicotinic acid. Stresses, including liver diseases, malabsorption, iron overload, porphyria, marasmus, cold stress, pregnancy, lactation, antibiotics and sulfa drugs, all increase dietary needs of nicotinic acid. Elevated free fatty acids and ketone bodies in the blood are associated with ketosis, zinc depletion and the pre-diabetic state. There is a diminished uptake of glucose by the tissues, a condition also found in parturient paresis of dairy cows when elevated hydrocortisone promotes insulin resistance and hyperglycaemia. This defect in insulin response leads to a diabetic-like state. The major predisposing factor in parturient paresis of dairy cows is hypocalcaemia. Gut absorption of dietary calcium may not meet the primary demands of lactation initiation until bone calcium mobilisation is established.
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PMID:Metabolic disorders of cattle. 839

Isovaleric acidemia, an autosomal recessive disorder, is due to isovaleryl-coenzyme A dehydrogenase deficiency and is one of the branched-chain aminoacidopathies. Isovaleric acidemia may present in the neonatal period with an acute episode of severe metabolic acidosis, ketosis, and vomiting and may lead to coma and death in the first 2 months of life. This report concerns an infant who presented at 10 days of age because of lethargy, poor feeding, hypothermia, cholestasis, and thrombocytopenia, leukopenia, and profound pancytopenia. Death occurred at 19 days of age. Autopsy showed mild fatty change in the liver and extramedullary hematopoiesis, generalized Escherichia coli sepsis, and myelodysplasia of the bone marrow with arrest of the myeloid series at the promyelocytic stage. The appearance resembled promyelocytic leukemia, but the diagnostic 15:17 translocation was not present. The maturation arrest in granulopoiesis in isovaleric acidemia appears to be most likely due to a direct metabolic effect on granulocyte precursor cells.
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PMID:Isovaleric acidemia with promyelocytic myeloproliferative syndrome. 1019 53


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