Hyperammonaemia and lactic acidosis in a patient with pyruvate dehydrogenase deficiency

Brown, Garry K.; Scholem, R. D.; Hunt, Simon A.; Harrison, J. R.; Pollard, A.C.

doi:10.1007/bf01799978

Cited by 41 publications

(14 citation statements)

References 22 publications

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“…The initially low values of plasma arginine and citrutline, the reduced orotic aciduria and the reaction of plasma ammonia to arginine treatment in our patient indicate that urea cycle dysfunction at the level of carbamylphosphate synthetase due to hypoargininaemia seems to have been the origin of her hyperammonaemia as also concluded by Brown et al [7]. Our experience suggests that arginine supplement is as effective as sodium benzoate [16] in the treatment of hyperammonaemia in PDHC deficiency.…”

Section: Discussionsupporting

confidence: 63%

“…Hyperammonaemia has been a complication of neonatal PDHC deficiency in 3 other patients [7,15,16]. The initially low values of plasma arginine and citrutline, the reduced orotic aciduria and the reaction of plasma ammonia to arginine treatment in our patient indicate that urea cycle dysfunction at the level of carbamylphosphate synthetase due to hypoargininaemia seems to have been the origin of her hyperammonaemia as also concluded by Brown et al [7].…”

Section: Discussionsupporting

confidence: 61%

“…Abbreviations: BCAA = branched chain amino acids; DCA = dichloroacetate; E1 = pyruvate decarboxylase; E2 = dihydrolipoyl transacetylase; E3 = dihydrolipoyl dehydrogenase; PDHC = pyruvate dehydrogenase complex of recent surveys and reviews [4,19,20,22] can present in the neonatal period with overwhelming lactic acidaemia and may be accompanied by hyperammonaemia [7,15,16]. The following is a report on the initial clinical presentation, acute treatment and a 1 year 8 month long clinical and biochemical follow-up in a case of neonatal PHDC deficiency with a fatal outcome.…”

Section: Offprint Requests To: D J Byrdmentioning

confidence: 99%

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Neonatal pyruvate dehydrogenase deficiency with lipoate responsive lactic acidaemia and hyperammonaemia

et al. 1989

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A 2-day-old girl developed a severe lactic acidosis with a normal lactate/pyruvate ratio and hyperammonaemia. Plasma arginine and citrulline levels were below the limit of detection. In muscle total pyruvate dehydrogenase complex (PDHC) and pyruvate decarboxylase (E1) activities were reduced to a fraction of lower control values. The acute neonatal period was bridged with peritoneal dialysis, dichloroacetate therapy, supplements of arginine and branched chain amino acids, a complete vitamin B complex and lipoic acid. Lactate homeostasis responded to pharmacological supplements of lipoic acid. At age 1 year the child was hypotonic, showed severe developmental retardation, optic atrophy and cranial dysmorphism. She died aged 1 year 8 months with signs of respiratory paralysis but with normal lactate levels under assisted breathing. Pathological findings at autopsy were suggestive of Leigh syndrome, interstitial pneumonia and extensive fatty infiltration of hepatocytes. Regression analysis of data from 187 plasma amino acid determinations from the patient over a period of 1 year 8 months revealed a persistent-imbalance involving alanine, glutamic acid, glutamine, proline, citrulline and branched chain amino acids. Aspects of acute and long-term therapy in this patient and some implications of the imbalances in plasma amino acids are discussed.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionsupporting

confidence: 61%

Section: Offprint Requests To: D J Byrdmentioning

confidence: 99%

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Neonatal pyruvate dehydrogenase deficiency with lipoate responsive lactic acidaemia and hyperammonaemia

et al. 1989

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“…A subset of patients with low E1 activity may have a defect in E1 activation (11). Other patients lack one or both of the subunit proteins (10)(11)(12). Since many E1-deficient patients have normal amounts of both E1 subunit proteins (10), at least one of the two subunits may be catalytically inactive.…”

mentioning

confidence: 99%

Characterization of cDNAs encoding human pyruvate dehydrogenase alpha subunit.

Wexler

Liu

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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“…In severe deficiencies of pyruvate dehydrogenase, this is probably due to depletion of intramitochondrial acetyl-CoA. 91 In pyruvate carboxylase deficiency, hyperammonaemia is explained by decreased carboxylation of pyruvate to oxaloacetate which, after transamination to aspartate, is a substrate for the urea cycle. 92 Severe organic acid disorders usually present in infancy and have a poor outcome without rapid, appropriate intervention.…”

Section: Organic Acid Disordersmentioning

confidence: 99%

Severe hyperammonaemia in adults not explained by liver disease

Walker

2012

Ann Clin Biochem

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Ammonia is produced continuously in the body. It crosses the blood-brain barrier readily and at increased concentration it is toxic to the brain. A highly integrated system protects against this: ammonia produced during metabolism is detoxified temporarily by incorporation into the non-toxic amino acid glutamine. This is transported safely in the circulation to the small intestine, where ammonia is released, carried directly to the liver in the portal blood, converted to non-toxic urea and finally excreted in urine. As a result, plasma concentrations of ammonia in the systemic circulation are normally very low (,40 mmol/L). Hyperammonaemia develops if the urea cycle cannot control the ammonia load. This occurs when the load is excessive, portal blood from the intestines bypasses the liver and/or the urea cycle functions poorly. By far, the commonest cause is liver damage. This review focuses on other causes in adults. Because they are much less common, the diagnosis may be missed or delayed, with disastrous consequences. There is effective treatment for most of them, but it must be instituted promptly to avoid fatality or long-term neurological damage. Of particular concern are unsuspected inherited defects of the urea cycle and fatty acid oxidation presenting with catastrophic illness in previously normal individuals. Early identification of the problem is the challenge.

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Hyperammonaemia and lactic acidosis in a patient with pyruvate dehydrogenase deficiency

Cited by 41 publications

References 22 publications

Neonatal pyruvate dehydrogenase deficiency with lipoate responsive lactic acidaemia and hyperammonaemia

Neonatal pyruvate dehydrogenase deficiency with lipoate responsive lactic acidaemia and hyperammonaemia

Characterization of cDNAs encoding human pyruvate dehydrogenase alpha subunit.

Severe hyperammonaemia in adults not explained by liver disease

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