Abstract
A 3-month-old girl presented with anorexia, failure to thrive and drowsiness. She was mildly icteric with hepatomegaly and peripheral oedema. Disordered liver function tests were associated with the biopsy appearances of a giant cell hepatitis and with a Fanconi syndrome. At the age of 16 weeks she collapsed with profound hypoglycaemia. Fasting also provoked hypoglycaemia with lactic acidaemia. She became increasingly irritable and hypotonic and, although initially liver and renal function improved, she deteriorated and died of hepatocellular failure and septicaemia. A post-mortem revealed massive fatty degeneration of the liver. The activity of phosphoenolpyruvate carboxykinase in her cultured skin fibroblasts was 16% of controls. Her brother died at the age of 4 weeks of sudden infant death syndrome.
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Abbreviations
- PEPCK:
-
phosphoenolpyruvate carboxykinase
- PEP:
-
phosphoenolpyruvate
- PC:
-
pyruvate carboxylase
References
Atkin BM, Utter MF, Weinberg MB (1979) Pyruvate carboxylase and phosphoenol pyruvate carboxykinase activity in leukocytes and fibroblasts from a patient with pyruvate carboxylase deficiency. Pediatr Res 13:38–43
Ballard FJ, Hanson RW (1967) Phosphoenolpyruvate carboxykinase and pyruvate carboxylase in developing rat liver. Biochem J 104:866–871
Ballard FJ, Hanson RW (1969) Purification of phosphoenolpyruvate carboxykinase from the cytosol fraction of rat liver and the immunochemical demonstration of differences between this enzyme and the mitochondrial phosphoenolpyruvate carboxykinase. J Biol Chem 244:5625–5630
Bartlett K, Ng H, Dale G, Green A, Leonard JV (1981) Studies on cultured fibroblasts from patients with defects of biotin-dependent carboxylation. J Inherited Metab Dis 4:183–189
Drahota Z, Rauchova H, Mikova M, Kaul P, Bass A (1983) Phosphoenolpyruvate shuttle-transport of energy from mitochondria to cytosol. FEBS Lett 157:347–349
Duffy TH, Markowitz PJ, Chuang DT, Utter MF, Nowak T (1981) Comparative inhibition of mitochondrial and cytosolic phosphoneol pyruvate carboxykinase by stereospecific substrate analogues. Proc Natl Acad Sci USA 78:6680–6683
Fiser RH, Melsher HL, Fisher DA (1974) Hepatic phosphoenolpyruvate carboxykinase deficiency — a new cause of hypoglycaemia in childhood. Pediatr Res 10:60
Hod Y, Utter MF, Hanson RW (1982) The mitochondrial and cytosolic forms of avian phosphoenolpyruvate carboxykinase (GTP) are encoded by different messenger RNA's. J Biol Chem 257:13787–13794
Hommes FA, Bendien K, Elema JD, Bremer HJ, Lombeck I (1976) Two cases of phosphoenolpyruvate carboxykinase deficiency. Acta Paediatr Scand 65:233–240
Hyland K, Leonard JV (1983) Revised assays for the investigation of congenital lactic acidosis using 14C-keto acids eliminating problems associated with spontaneous decarboxylation. Clin Chim Acta 133:177–187
Lardy HA (1975) Enzyme lack tied to sudden infant deaths. Chem Eng News 53:7–8
McGarry JD, Foster DW (1980) Regulation of hepatic fatty acid oxidation and ketone body production. Ann Rev Biochem 49:395–420
Pogell BM, Tanaka A, Siddons RC (1968) Natural activators for liver fructose-1-6-diphosphatase and reversal of inhibition by adenosine 5-monophosphate by muscle phosphofructokinase. J Biol Chem 243:1356–1367
Robinson BH, Taylor J, Kahler S (1979) Mitochondrial phosphoenolpyruvate carboxykinase deficiency in a child with lactic acidaemia, hypotonia and failure to thrive. Am J Hum Genet 31: 60A
Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown MS (1983) The metabolic basis of inherited disease. McGraw Hill, New York
Sturner WQ, Susa JB (1980) Sudden infant death and liver phosphoenolpyruvate carboxykinase analysis. Forensic Sci Int 16:19–28
Sumbilla CM, Zielke HR, Krausse BL, Oxand PT (1983) Gluconeogenic enzymes in fibroblasts from infants dying of the sudden infant death syndrome (SIDS). Eur J Pediatr 140:276–277
Vidnes J, Sovik O (1976) Gluconeogenesis in infancy and childhood. III. Deficiency of the extramitochondrial form of hepatic phosphoenolpyruvate carboxykinase in a case of persistent neonatal hypoglycaemia. Acta Paediatr Scand 65:307–312
Watford M, Hod Y, Chiao Y-B, Utter MF, Hanson RW (1981) The unique role of the kidney in gluconeogenesis in the chicken. J Biol Chem 256:10023–10027
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Clayton, P.T., Hyland, K., Brand, M. et al. Mitochondrial phosphoenolpyruvate carboxykinase deficiency. Eur J Pediatr 145, 46–50 (1986). https://doi.org/10.1007/BF00441851
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DOI: https://doi.org/10.1007/BF00441851