11/24. Ketotic hypoglycemia and hypopituitarism.A 5-year-old girl had hypoglycemia and was of short stature. Studies of pituitary function demonstrated combined growth hormone and adrenocorticotropic hormone (ACTH) deficiency. She was shown to have ketotic hypoglycemia. In contrast to patients previously reported with hypopituitarism and ketotic hypoglycemia, she had no deficiency of gluconeogenic substrate. serum levels of alanine and other gluconeogenic amino acids were normal during fasting and hypoglycemia. These studies suggest that inadequate gluconeogenic precursors are not the cause of her ketotic hypoglycemia. Ketotic hypoglycemia in association with hypopituitarism may be secondary to multiple biochemical defects.- - - - - - - - - - ranking = 1keywords = deficiency (Clic here for more details about this article) |
12/24. Acute neonatal nonketotic hyperglycinemia: normal propionate and methylmalonate metabolism.Propionyl-CoA carboxylase and combined methylmalonyl-CoA (MMA-CoA) racemase and -mutase activities were studied in liver and fibroblasts of two patients with the acute neonatal form of nonketotic hyperglycemia. In all experiments, these enzyme activities studied in tissues of the patients were within the range of healthy control subjects, whereas no propionyl-CoA carboxylase activity was measurable in the fibroblasts of a patient with propionic acidemia. Subcellular fractionation of liver and fibroblasts indicated that the normal amounts of MMA-CoA found after incubation of whole tissue homogenate were formed by propionyl-CoA carboxylase, a mitochondrial enzyme, and not be acetyl-coa carboxylase, which theoretically could also be involved in the carboxylation of propionyl-CoA. From the above data as well as from clinical and biochemical observations in three patients, it was concluded that there exists a true nonketotic hyperglycinemia which is not related etiologically to the different disorders of the ketotic hyperglycinemia syndrome. True nonketotic hyperglycinemia is not associated with ketoacidosis even after loading with propionate- and MMA precursors. It must be distinguished by exclusion from mild forms of the ketotic hyperglycinemia syndrome which may present clinically as hyperglycinemia without ketosis.- - - - - - - - - - ranking = 166.85770587459keywords = carboxylase (Clic here for more details about this article) |
13/24. Acetoacetyl CoA thiolase deficiency presenting as ketotic hypoglycemia.We report two children who presented with hypoglycemia and metabolic acidosis in whom acetoacetyl-CoA thiolase (EC 2.3.1.9) measured in fibroblast homogenates was deficient. Deficiency of this enzyme is normally associated with urinary excretion of 2-methylacetoacetate and in one child the urinary excretion of 2-methylacetoacetate, 2-methyl-3-hydroxybutyrate, and tiglylglycine was raised. By contrast, in the other child, the urinary excretion of these metabolites was very low even during ketoacidosis and following an isoleucine load. We suggest that this could be due to deficiency of the extrahepatic isoenzyme, a defect that may be responsible for some of the cases of "ketotic hypoglycemia."- - - - - - - - - - ranking = 2.5keywords = deficiency (Clic here for more details about this article) |
14/24. Isolated glucocorticoid deficiency: metabolic and endocrine studies in a 5-year-old boy.A 5-year-old boy is described who presented with episodes of hypoglycaemia triggered by mild infections or fever. Subnormal glucocorticoid production was confirmed by demonstrating low urinary excretion of free cortisol, low plasma cortisol concentrations that did not rise after glucagon and ACTH stimulation, and by elevated plasma ACTH levels. The selective nature of the abnormality was confirmed by demonstrating normal plasma electrolyte concentrations and blood pressure on a salt-restricted diet. plasma renin activity and plasma aldosterone levels were also normal and responded appropriately to salt restriction and to frusemide-induced diuresis. starvation-induced hypoglycaemia was associated with raised levels of blood ketone bodies and low blood alanine concentrations. Catecholamine secretion during hypoglycaemia was reduced. Glucocorticoid replacement therapy was effective in restoring normal glucose homeostasis.- - - - - - - - - - ranking = 2keywords = deficiency (Clic here for more details about this article) |
15/24. Clinical and laboratory observations in a child with hepatic phosphorylase kinase deficiency.A 3-year-old child with glycogenosis due to hepatic phosphorylase kinase deficiency is described. His clinical presentation was unusually severe. Biochemical studies revealed a lack of hypoglycemia, the presence of marked ketosis and hyperlipidemia, and a normal glycemic response to glucagon and to loading with galactose, fructose, and alanine. The ketosis was reversed by glucagon administration. Changes in plasma concentrations of lactate, pyruvate, beta-OH butyrate, and alanine in response to glucagon, galactose, fructose, and alanine administration are reported. The child responded poorly to a high protein diet. His condition improved markedly with a high carbohydrate diet. The significance of the findings is discussed.- - - - - - - - - - ranking = 2.5keywords = deficiency (Clic here for more details about this article) |
16/24. Acetoacetyl CoA thiolase deficiency: a cause of severe ketoacidosis in infancy simulating salicylism.A female child presented at one year of age with a febrile illness and loose stools, then developed severe ketoacidosis with vomiting; an apparent salicylate level of 11 mg/dl was measured. A sibling had died in similar circumstances nine years earlier. Investigation revealed that the child did not have salicylate intoxication, and that high levels of acetoacetate in blood and urine were giving readings indicative of the presence of salicylate on routine testing. Gas-liquid chromatographic analysis combined with mass spectrometry on urine samples revealed the presence of 2-methyl-acetoacetate, 2-methyl-3-hydroxybutyrate, and tiglyl glycine in appreciable amounts, indicating a defect in isoleucine catabolism located at the beta-ketothiolase step. The oxidation of 14C-isoleucine to CO2 in cultured fibroblasts confirmed that this pathway was defective. We present evidence that beta-ketothiolase deficiency is not simply a defect of isoleucine degradation; the deficient enzyme is the K dependent short-chain mitochondrial thiolase, which also plays a major catalytic role in ketone body and fatty acid oxidation.- - - - - - - - - - ranking = 2.5keywords = deficiency (Clic here for more details about this article) |
17/24. Medium-chain acyl-CoA dehydrogenase deficiency in children with non-ketotic hypoglycemia and low carnitine levels.Three children in two families presented in early childhood with episodes of illness associated with fasting which resembled Reye's syndrome: coma, hypoglycemia, hyperammonemia, and fatty liver. One child died with cerebral edema during an episode. Clinical studies revealed an absence of ketosis on fasting (plasma beta-hydroxybutyrate less than 0.4 mmole/liter) despite elevated levels of free fatty acids (2.6-4.2 mmole/liter) which suggested that hepatic fatty acid oxidation was impaired. Urinary dicarboxylic acids were elevated during illness or fasting. Total carnitine levels were low in plasma (18-25 mumole/liter), liver (200-500 nmole/g), and muscle (500-800 nmole/g); however, treatment with L-carnitine failed to correct the defect in ketogenesis. Studies on ketone production from fatty acid substrates by liver tissue in vitro showed normal rates from short-chain fatty acids, but very low rates from all medium and long-chain fatty acid substrates. These results suggested that the defect was in the mid-portion of the intramitochondrial beta-oxidation pathway at the medium-chain acyl-CoA dehydrogenase step. A new assay for the electron transfer flavoprotein-linked acyl-coa dehydrogenases was used to test this hypothesis. This assay follows the decrease in electron transfer flavoprotein fluorescence as it is reduced by acyl-CoA-acyl-CoA dehydrogenase complex. Results with octanoyl-CoA as substrate indicated that patients had less than 2.5% normal activity of medium-chain acyl-CoA dehydrogenase. The activities of short-chain and isovaleryl acyl-coa dehydrogenases were normal; the activity of long-chain acyl-CoA dehydrogenase was one-third normal. These results define a previously unrecognized inherited metabolic disorder of fatty acid oxidation due to deficiency of medium-chain acyl-CoA dehydrogenase.- - - - - - - - - - ranking = 2.5keywords = deficiency (Clic here for more details about this article) |
18/24. Propionyl coenzyme a carboxylase deficiency presenting as non-ketotic hyperglycinaemia.A 4-month-old girl presented with myoclonic seizures and an electroencephalogram showing hypsarrhythmia. Hyperglycinuria and a cerebrospinal fluid to plasma glycine ratio of 0.2 suggested the diagnosis of non-ketotic hyperglycinaemia. Propionic acid and methyl citric acid were present in the urine, and propionyl coenzyme a carboxylase was deficient in leucocytes and fibroblasts. The ketotic and non-ketotic hyperglycinaemias cannot be differentiated by CSF: plasma glycine ratios.- - - - - - - - - - ranking = 1349.8989991239keywords = carboxylase deficiency, carboxylase, deficiency (Clic here for more details about this article) |
19/24. Impaired ketogenesis in fructose-1,6-bisphosphatase deficiency: a pitfall in the investigation of hypoglycaemia.Intermediary metabolite concentrations were measured in blood during fasting in two patients with fructose-1,6-bisphosphatase deficiency. Hypoglycaemia was accompanied by markedly raised levels of plasma free fatty acids, without the expected degree of ketosis. This suggests that there is secondary impairment of ketogenesis in this condition, and could lead to diagnostic confusion.- - - - - - - - - - ranking = 2.5keywords = deficiency (Clic here for more details about this article) |
20/24. Congenital lacticacidemia caused by lipoamide dehydrogenase deficiency with favorable outcome.A 5-year-old boy had recurrent vomiting and lethargy with lacticacidemia and ketoacidemia since birth. Lipoamide dehydrogenase deficiency was found in muscle and fibroblasts. Therapy with sodium dichloroacetate, thiamine, and carnitine was associated with reduction of the severity and frequency of the decompensation episodes and near normal plasma lactate levels. At 5 years of age, the patient has normal cognitive function and moderate motor impairment.- - - - - - - - - - ranking = 2.5keywords = deficiency (Clic here for more details about this article) |
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