Neonatal Congenital Lactic Acidosis With Pyruvate Carboxylase Deficiency in Two Siblings

Saudubray, Jean Marie; Marsac, Cécile; Charpentier, C.; Cathelineau, L; LEAUD, M. BESSON; Leroux, Jean‐Paul

doi:10.1111/j.1651-2227.1976.tb04960.x

Cited by 35 publications

(45 citation statements)

References 21 publications

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“…Both authors postulated a prenatal origin of lesions. Ventricular enlargement with cystic degeneration of the periventricular white matter was also reported on neuropathological examination in three cases with the severe form of PC deficiency who died at age 3, 4, and 12 weeks, respectively [Saudubray et al, 1976;Rutledge et al, 1989]. Thus, all seven cases with the B form of PC deficiency for whom neurological imaging or pathology are available had confirmed cystic degeneration of periventricular white matter.…”

Section: Discussionmentioning

confidence: 70%

Pyruvate carboxylase deficiency: Prenatal onset of ischemia-like brain lesions in two sibs with the acute neonatal form

et al. 1999

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Pyruvate carboxylase (PC) is a key enzyme in the gluconeogenesis and anaplerotic metabolic pathways. PC deficiency is a rare autosomal recessive disorder with three clinical presentations: an infantile form, a severe neonatal form, and a benign form. We report brother and sister sibs with the severe form of PC deficiency. Both had macrocephaly and severe ischemia-like brain lesions at birth and died in the first week of life with intractable lactic acidemia. In the girl, increased head circumference and periventricular leukomalacia (PVL) were detected on fetal ultrasonography at 29.4 weeks of gestation. PC activity in cultured skin fibroblasts was <2% of control. This is the first reported case of ischemia-like brain lesions documented prenatally in PC deficiency. The lesions were detected at a time of maximal periventricular metabolic demand. We postulate that energy deprivation induced by PC deficiency impairs astrocytic buffering capacity against excitotoxic insult and compromises normal microvascular morphogenesis and autoregulation, both mechanisms leading to cystic degeneration of the periventricular white matter. Discovery of cystic PVL on cerebral ultrasound at birth in a newborn infant presenting with primary lactic acidemia is highly suggestive of PC deficiency. Moreover, PC deficiency should also be considered when ischemia-like brain lesions are documented by fetal ultrasonography.

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Section: Discussionmentioning

confidence: 70%

Pyruvate carboxylase deficiency: Prenatal onset of ischemia-like brain lesions in two sibs with the acute neonatal form

et al. 1999

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“…Saudubray et al (8) described hepatomegaly with steatosis. The pathology of the present case is relatively specific in resembling both hereditary fructose intolerance and galactosemia.…”

Section: Discussionmentioning

confidence: 99%

Biochemical and Histologic Pathology in an Infant with Cross-Reacting Material (Negative) Pyruvate Carboxylase Deficiency

et al. 1986

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ABSTRACT. An infant with the acute neonatal form of pyruvate carboxylase deficiency (cross-reacting material negative) presented with severe intractable lactic acidosis within 4 h after birth. He also had hyperammonemia, hypercitrullinemia, and hyperlysinemia. Plasma glutamine was not elevated. He had a rapidly deteriorating clinical course with severe liver dysfunction, repeated septicemia and seizures; he was comatose and was on a ventilator throughout; death occurred at 8 wk of age. Skin fibroblast study confirmed the enzyme deficiency. Detailed biochemical parameters and histopathology of the brain and liver are presented. The evidence from this infant suggests that disturbances of intracellular oxaloacetate levels as a result of the primary enzyme defect might also contribute to deficiency in ATP generation which may explain the various other biochemical changes and liver pathology. There are two main forms of the disease-the acute neonatal and infantile forms. The acute neonatal form of this condition was first described by Coude and coworkers (1, 2). Their patients followed a rapidly malignant course and died within the first months of life. Besides severe intractable lactic acidosis (levels of 10 to 20 mM), there were other biochemical abnormalities including hyperammonemia (in the range of 100 to 300 pM), citrullinemia (up to 400 pM), lysinemia (up to 800 pM), elevated lactate-pyruvate ratio (range 50-loo), and a lowered P-hydroxy butyrate-acetoacetate ratio (less than 1). Skin fibroblasts cultured from patients with this acute neonatal form of PC deficiency have recently been shown to have complete absence of a protein recognized by anti-PC antibodies, i.e. they were CRM negative (3). Patients presenting with milder infantile forms of the disease had immunologically detectable PC (i.e. CRM positive). The two groups were indistinguishable by assays of enzyme activity.We describe the detailed clinical and biochemical course together with the histopathology of one PC-deficient (CRM nega- tive) patient. This patient is one of the group described earlier (3). Because only an extremely abbreviated clinical description was possible in the earlier paper and because we believe that the symptomatology as well as the biochemical aberrations and histopathology have important implications we therefore present this patient's findings in more detail. METHODSBlood ammonia, lactate, and bilirubin were assayed by the Dupont aca (1 3); electrolytes by Beckman ASTRA system; blood pH and bicarbonate by the Corning pH/Blood Gas Analyser (13); and serum alkaline phosphatase, aspartate transaminase, alanine transaminase, by the Technicon RA-1000 (13). Plasma and urinary amino acids were assayed by methods previously described (4, 5). Urine organic acids were examined using the Hewlett-Packard 5992A GC/MS (6). Plasma acetoacetate and Phydroxybutyrate were assayed according to the micromethod of Persson (7). Plasma pyruvate was assayed using Sigma kit no. 726 (these are trademarks of the respective companies, protected by appro...

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“…hyperammonemia (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Essentially all these patients died within the first 4 mo of life.…”

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confidence: 99%

Pyruvate Carboxylase Deficiency: A Benign Variant with Normal Development

1991

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ABSTRACT. The devastating nature of a pyruvate carboxylase deficiency is underscored by the uniformly fatal outcome of the neonatal (French) type and the severely disabling and ultimately fatal outcome of the infantile (North American) type. We report a 7-y-old girl with metabolic and biochemical features of the North American phenotype. Remarkably, the clinical course has been benign with preservations of motor and mental abilities. The residual enzyme activity in cultured skin fibroblast homogenates was 1.8% and cross-reacting material was present in normal abundance and electrophoretic mobility. She has had several episodes of metabolic acidosis with elevated lactate, pyruvate, alanine, 0-hydroxybutyrate, acetoacetate, lysine, and proline values, and undetectably low aspartate concentrations. These crises have been managed by rehydration and bicarbonate therapy. We are unable to provide a satisfactory explanation for the uniquely benign clinical course that has been experienced by this patient. (Pediatr Res 30: 1-4, 1991)

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Neonatal Congenital Lactic Acidosis With Pyruvate Carboxylase Deficiency in Two Siblings

Cited by 35 publications

References 21 publications

Pyruvate carboxylase deficiency: Prenatal onset of ischemia-like brain lesions in two sibs with the acute neonatal form

Pyruvate carboxylase deficiency: Prenatal onset of ischemia-like brain lesions in two sibs with the acute neonatal form

Biochemical and Histologic Pathology in an Infant with Cross-Reacting Material (Negative) Pyruvate Carboxylase Deficiency

Pyruvate Carboxylase Deficiency: A Benign Variant with Normal Development

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