1/12. Treatment of pyruvate carboxylase deficiency with high doses of citrate and aspartate.A patient with severe pyruvate carboxylase deficiency presented at age 11 weeks with metabolic decompensation after routine immunization. She was comatose, had severe lactic acidemia (22 mM) and ketosis, low aspartate and glutamate, elevated citrulline and proline, and mild hyperammonemia. head magnetic resonance imaging showed subdural hematomas and mild generalized brain atrophy. biotin-unresponsive pyruvate carboxylase deficiency was diagnosed. To provide oxaloacetate, she was treated with high-dose citrate (7.5 mol/kg(-1)/day(-1)), aspartate (10 mmol/kg(-1)/day(-1)), and continuous drip feeding. Lactate and ketones diminished dramatically, and plasma amino acids normalized, except for arginine, which required supplementation. In the cerebrospinal fluid (CSF), glutamine remained low and lysine elevated, showing the treatment had not normalized brain chemistry. Metabolic decompensations, triggered by infections or fasting, diminished after the first year. They were characterized by severe lactic and ketoacidosis, hypernatremia, and a tendency to hypoglycemia. At age 3(1/2) years she has profound mental retardation, spasticity, and grand mal and myoclonic seizures only partially controlled by anticonvulsants. The new treatment regimen has helped maintain metabolic control, but the neurological outcome is still poor.- - - - - - - - - - ranking = 1keywords = brain (Clic here for more details about this article) |
2/12. Alcohol induced ketoacidosis, severe hypoglycemia and irreversible encephalopathy.BACKGROUND: Severe hypoglycemia leading to permanent brain damage is rare in non-diabetic population. We present one such case where chronic alcoholism combined with prolonged fasting lead to such a state and patient ended in a persistent vegetative state. CASE REPORT: A 50 year old Asian woman with past history of chronic alcoholism and hepatitis c was found unresponsive in her house after drinking alcohol consecutively for 2 days. Finger-stick glucose done by paramedics was <20 mg/dl. She was given 50 ml of 50% dextrose without any neurological response. On arrival in the emergency department patient was found to be comatose with only withdrawal response to deep painful stimuli and a negative babinski's sign. Computed tomogram of the head revealed mild cerebral atrophy. After an extensive work up a diagnosis of alcoholic ketoacidosis with hypoglycemia related encephalopathy was made. CONCLUSIONS: Alcohol induced ketoacidosis is usually associated with normal blood glucose. The probable etiology of low blood sugar in our patient was alcohol-induced inhibition of gluconeogenesis along with starvation. The prolonged hypoglycemia caused cortical damage simulating ischemic brain damage. Ten months in to follow-up patient is still in persistent vegetative state with no noticeable neurological recovery.- - - - - - - - - - ranking = 1keywords = brain (Clic here for more details about this article) |
3/12. Severe acidosis caused by starvation and stress.A 1-year-old boy had severe anoxic brain injury owing to a cardiorespiratory arrest. He had an initial metabolic acidosis, but this largely resolved by hospital day 2. He then had a persistent, profound metabolic acidosis. Evaluation on hospital day 6 found that the patient had ketonemia, ketonuria, and a normal serum glucose level; he had received no intravenous dextrose during his hospitalization. The dextrose-free fluids were given initially to protect his brain from the deleterious effects of hyperglycemia after brain injury. Continuation beyond 24 hours was inadvertent. The initiation of dextrose-containing intravenous fluids produced a rapid resolution of his metabolic acidosis. starvation usually produces a mild metabolic acidosis, but when combined with physiologic stress, starvation may cause a severe metabolic acidosis. Among the few reports of severe starvation ketoacidosis, our case is unique because the patient was monitored closely in an intensive care unit, allowing us to describe the time course of the acidosis in detail.- - - - - - - - - - ranking = 1.5keywords = brain (Clic here for more details about this article) |
4/12. Ketotic hypoglycaemia in children with diazoxide responsive hyperinsulinism of infancy.hyperinsulinism of infancy (HI) is a cause of persistent and recurrent hypoglycaemia in infancy and childhood, which if untreated can cause significant brain damage and mental retardation. The biochemical hallmark of hyperinsulinism is hypofattyacidaemic, hypoketotic hyperinsulinaemic hypoglycaemia. diazoxide is the first line medical treatment for persistent HI. diazoxide is an agonist of the pancreatic beta-cell KATP channel and inhibits insulin secretion. Children who develop recurrent hypoglycaemia while on therapy with diazoxide are thought to be unresponsive to this medication or non compliant with medical therapy. We report a novel observation of "ketotic" hypoglycaemia in two children on diazoxide therapy for persistent HI. Detailed assessment of the intermediary metabolites and hormones at the time of the hypoglycaemia showed appropriate insulin suppression with appropriate increases in the serum levels of non-esterified fatty acids and ketone bodies as well as an intact counter-regulatory hormone response. The precise mechanism of the hypoglycaemia is unclear. CONCLUSION: These cases illustrate that recurrent hypoglycaemia while on diazoxide therapy may be due to other mechanisms and does not imply diazoxide unresponsiveness or non-compliance.- - - - - - - - - - ranking = 0.5keywords = brain (Clic here for more details about this article) |
5/12. Hallermann-Streiff syndrome with hypopituitarism contributing to growth failure.A 35-month-old black boy with Hallermann-Streiff syndrome (HSS) was evaluated for anterior hypopituitarism when he presented with ketotic hypoglycemia, microgenitalia, and short stature. Endocrine evaluation showed a low T4 and TSH levels, suggesting hypothalamic hypothyroidism; this was confirmed by TRH stimulation. metyrapone test confirmed ACTH deficiency as a contributing factor to the ketotic hypoglycemia. A superagonist GnRH test suggested hypothalamic GnRH deficiency. growth hormone provocative testing conclusively demonstrated complete growth hormone deficiency. MRI investigation of the brain suggested hypopituitarism. Although facial findings were not completely classical of the HSS, we suggest these may be somewhat altered due to his racial back-ground. We recommend endocrine evaluation of HSS patients with manifestations suggesting hypopituitarism since treatment of this condition will improve the quality of life of these patients.- - - - - - - - - - ranking = 0.5keywords = brain (Clic here for more details about this article) |
6/12. Lactic acidosis in childhood.Children with chronic metabolic acidosis should be investigated to determine the presence of an organic acid, especially when the plasma electrolyte profile shows a deficiency of anion. One of the organic acids that should be looked for in such a patient is lactic acid. Lactic acidosis due to tissue hypoxia is a well-known phenomenon (e.g., in shock and cardiopulmonary disease) and has not been discussed in this essay; nor has lactic acidosis due to exogenous causes like infusion of fructose or sorbitol, or admiministration of phenformin. Chronic lactic acidosis in infancy is a rare condition. It may be associated with glycogen storage disease Type 1, fructose diphosphatase deficiency, methylmalonic acidemia, propionic acidemia, pyruvate carboxylase or dehydrogenase deficiency and Leigh's subacute necrotizing encephalomyelopathy (SNE). Some patients with chronic lactic acidosis do not have nay of these diseases and comprise an "idiopathic" group. This is a heterogeneous group, probably having several different causes for the metabolic error. In Leigh's SNE, a metabolic block in the formation of thiamine triphosphate in brain has been demonstrated and has been attributed to the presence of an inhibitor of thiamine pyrophosphate-adenosine triphosphate (TPP-ATP) phosphoryl transferase in body fluids. The inhibitor has also been encountered in cases of intermittent cerebellar ataxia and of primary hypoventilation (Ondine's curse), which may represent variants of Leigh's disease. Increased blood levels of lactate, pyruvate and alanine frequently are encountered in SNE, but it still is not clear whether they are due to a primary or secondary disturbance in the catabolism of pyruvate. Disturbed lactate and pyruvate metabolism has also been encountered in isolated cases of mental retardation and growth failure, in mitochondrial myopathies and in polyneuropathies, and may be expected to occur in Wernicke's encephalopathy. Finally, it has been noted in malignancy and in association with other rare metabolic disorders.- - - - - - - - - - ranking = 765.04300622837keywords = metabolic disorder, brain (Clic here for more details about this article) |
7/12. Hyperglycinaemia without ketosis.When screening mentally backward children we detected a 5-year-old child with elevated urinary glycine excretion and a high blood glycine level. The report discusses the results of a clinical, metabolic and genetic examination of the child and the members of his family with reference to this rare metabolic disorder.- - - - - - - - - - ranking = 764.54300622837keywords = metabolic disorder (Clic here for more details about this article) |
8/12. Nonketotic hyperglycinemia: two patients with primary defects of P-protein and T-protein, respectively, in the glycine cleavage system.The glycine cleavage system was investigated in the livers and brains of two patients with typical nonketotic hyperglycinemia who died in the neonatal period. The overall activity of the glycine cleavage system was found to be extremely low in both the liver and brain of each patient. In one patient, the disturbance of the glycine cleavage system was due to absence of activity of the P-protein. Immunochemical analysis indicated that this resulted from an absence of the enzyme protein. In the other patient, the activity of the T-protein was undetectable in the brain and was extremely low in the liver. Clinically classic nonketotic hyperglycinemia resulted from molecular defects in two different protein components of the glycine cleavage system.- - - - - - - - - - ranking = 1.5keywords = brain (Clic here for more details about this article) |
9/12. A treatment of non-ketotic hyperglycinaemia.The treatment comprising a special diet (without glycine, serine, and with a reduced amount of threonine), strychnine nitrate and ursodesoxycholic acid (UDCA) led to normoglycinaemia in this form of severe non-ketotic glycine encephalopathy. diet and treatment were well tolerated but without significant effect upon psychomotor development. This treatment should be more effective if administered before irreversible brain damage occurs, particularly in moderate and chronic forms of NKH.- - - - - - - - - - ranking = 0.5keywords = brain (Clic here for more details about this article) |
10/12. 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 = 764.54300622837keywords = metabolic disorder (Clic here for more details about this article) |
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