Lactic Acidaemia

Overview

Journal J Inherit Metab Dis

Publisher Wiley

Date 1984 Jan 1

PMID 6434848

Citations 25

Authors

B H Robinson

W G Sherwood

Affiliations

Soon will be listed here.

Abstract

Congenital childhood lactic acidaemia is a poorly understood group of genetic diseases. The most common underlying inherited defect encountered in this group is deficiency of the pyruvate dehydrogenase complex. Of 23 cases we have diagnosed, 18 have a deficiency in the first component of the complex, the E1 decarboxylase, while the other five have multiple alpha-keto acid dehydrogenase deficiency due to a defect in lipoamide dehydrogenase. In addition to the lactic acidosis associated with pyruvate decarboxylase deficiency, ten of the cases showed evidence of facial dysmorphism consisting of a narrow head, wide nasal bridge and flared nostrils or gross microcephaly. Two further patients had agenesis of the corpus callosum. Isolated pyruvate carboxylase deficiency was found to present in two different forms, one with lactic acidaemia and mental retardation, the other with lactic acidaemia, hyperammonaemia citrullinaemia and hyperlysinaemia. The former presentation we have shown to be associated with the presence of a biotinylated pyruvate carboxylase protein of the correct subunit molecular weight (125 kd) which has no catalytic activity (CRM + ve). The latter we have shown to be associated with the absence of any recognizable pyruvate carboxylase protein (CRM - ve).

Citing Articles

Prenatal and Postnatal Diagnosis and Genetic Background of Corpus Callosum Malformations and Neonatal Follow-Up.

Bartek V, Szabo I, Harmath A, Rudas G, Steiner T, Fintha A Children (Basel). 2024; 11(7).

PMID: 39062246 PMC: 11274835. DOI: 10.3390/children11070797.

Microenvironmental control of glucose metabolism in tumors by regulation of pyruvate dehydrogenase.

Golias T, Kery M, Radenkovic S, Papandreou I Int J Cancer. 2018; 144(4):674-686.

PMID: 30121950 PMC: 6689402. DOI: 10.1002/ijc.31812.

MRPS22 mutation causes fatal neonatal lactic acidosis with brain and heart abnormalities.

Baertling F, Haack T, Rodenburg R, Schaper J, Seibt A, Strom T Neurogenetics. 2015; 16(3):237-40.

PMID: 25663021 DOI: 10.1007/s10048-015-0440-6.

Thiamine-Responsive and Non-responsive Patients with PDHC-E1 Deficiency: A Retrospective Assessment.

van Dongen S, Brown R, Brown G, Thorburn D, Boneh A JIMD Rep. 2014; 15:13-27.

PMID: 24718837 PMC: 4270867. DOI: 10.1007/8904_2014_293.

The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients.

Patel K, OBrien T, Subramony S, Shuster J, Stacpoole P Mol Genet Metab. 2011; 105(1):34-43.

PMID: 22079328 PMC: 3754811. DOI: 10.1016/j.ymgme.2011.09.032.

References

Robinson B, Sherwood W, Oei J . The development of pyruvate dehydrogenase in the subhuman primate Macaca mulatta. Biol Neonate. 1977; 32(3-4):154-7. DOI: 10.1159/000241010. View

Saunders M, Sweetman L, Robinson B, Roth K, Cohn R, Gravel R . Biotin-response organicaciduria. Multiple carboxylase defects and complementation studies with propionicacidemia in cultured fibroblasts. J Clin Invest. 1979; 64(6):1695-702. PMC: 371324. DOI: 10.1172/JCI109632. View

Haworth J, Robinson B, Perry T . Lactic acidosis due to pyruvate carboxylase deficiency. J Inherit Metab Dis. 1981; 4(2):57-8. DOI: 10.1007/BF02263589. View

Pettit F, PELLEY J, Reed L . Regulation of pyruvate dehydrogenase kinase and phosphatase by acetyl-CoA/CoA and NADH/NAD ratios. Biochem Biophys Res Commun. 1975; 65(2):575-82. DOI: 10.1016/s0006-291x(75)80185-9. View

Bartlett K, GOMPERTZ D . Biotin activation of carboxylase activity in cultured fibroblasts from a child with a combined carboxylase defect. Clin Chim Acta. 1978; 84(3):399-401. DOI: 10.1016/0009-8981(78)90255-3. View

Robinson B, Sherwood W . Pyruvate dehydrogenase phosphatase deficiency: a cause of congenital chronic lactic acidosis in infancy. Pediatr Res. 1975; 9(12):935-9. DOI: 10.1203/00006450-197512000-00015. View

Blass J, Kark A, Engel W . Clinical studies of a patient with pyruvate decarboxylase deficiency. Arch Neurol. 1971; 25(5):449-60. DOI: 10.1001/archneur.1971.00490050083007. View

Sorbi S, Blass J . Abnormal activation of pyruvate dehydrogenase in Leigh disease fibroblasts. Neurology. 1982; 32(5):555-8. DOI: 10.1212/wnl.32.5.555. View

Robinson B, Oei J, Saunders M, GRAVEL R . [3H]biotin-labeled proteins in cultured human skin fibroblasts from patients with pyruvate carboxylase deficiency. J Biol Chem. 1983; 258(10):6660-4. View

10.

Blass J, Avigan J, UHLENDORF B . A defect in pyruvate decarboxylase in a child with an intermittent movement disorder. J Clin Invest. 1970; 49(3):423-32. PMC: 322489. DOI: 10.1172/JCI106251. View

11.

Blass J, Lonsdale D, UHLENDORF B, Hom E . Intermittent ataxia with pyruvate-decarboxylase deficiency. Lancet. 1971; 1(7712):1302. DOI: 10.1016/s0140-6736(71)91822-8. View

12.

FARRELL D, Clark A, Scott C, Wennberg R . Absence of pyruvate decarboxylase activity in man: a cause of congenital lactic acidosis. Science. 1975; 187(4181):1082-4. DOI: 10.1126/science.803713. View

13.

Willems J, Monnens L, Trijbels J, Veerkamp J, MEYER A, van Dam K . Leigh's encephalomyelopathy in a patient with cytochrome c oxidase deficiency in muscle tissue. Pediatrics. 1977; 60(6):850-7. View

14.

Coude F, Ogier H, Marsac C, Munnich A, Charpentier C, Saudubray J . Secondary citrullinemia with hyperammonemia in four neonatal cases of pyruvate carboxylase deficiency. Pediatrics. 1981; 68(6):914. View

15.

Bartlett K, Ghneim H, Stirk J, Dale G, Alberti K . Pyruvate carboxylase deficiency. J Inherit Metab Dis. 1984; 7 Suppl 1:74-8. DOI: 10.1007/BF03047379. View

16.

Taylor J, Robinson B, Sherwood W . A defect in branched-chain amino acid metabolism in a patient with congenital lactic acidosis due to dihydrolipoyl dehydrogenase deficiency. Pediatr Res. 1978; 12(1):60-2. DOI: 10.1203/00006450-197801000-00018. View

17.

Chuang D, Ku L, Cox R . Thiamin-responsive maple-syrup-urine disease: decreased affinity of the mutant branched-chain alpha-keto acid dehydrogenase for alpha-ketoisovalerate and thiamin pyrophosphate. Proc Natl Acad Sci U S A. 1982; 79(10):3300-4. PMC: 346403. DOI: 10.1073/pnas.79.10.3300. View

18.

Linn T, Pettit F, Hucho F, Reed L . Alpha-keto acid dehydrogenase complexes. XI. Comparative studies of regulatory properties of the pyruvate dehydrogenase complexes from kidney, heart, and liver mitochondria. Proc Natl Acad Sci U S A. 1969; 64(1):227-34. PMC: 286151. DOI: 10.1073/pnas.64.1.227. View

19.

Robinson B, Taylor J, Sherwood W . The genetic heterogeneity of lactic acidosis: occurrence of recognizable inborn errors of metabolism in pediatric population with lactic acidosis. Pediatr Res. 1980; 14(8):956-62. DOI: 10.1203/00006450-198008000-00013. View

20.

Stromme J, BORUD O, MOE P . Fatal lactic acidosis in a newborn attributable to a congenital defect of pyruvate dehydrogenase. Pediatr Res. 1976; 10(1):62-6. DOI: 10.1203/00006450-197601000-00012. View