Pyruvate Carboxylase Deficiency and Lactic Acidosis in a Retarded Child without Leigh's Disease

Atkin, Beth M; Buist, Neil R. M.; Utter, Merton F.; Leiter, Andrew B.; Banker, Betty Q.

doi:10.1203/00006450-197902000-00005

Cited by 86 publications

(29 citation statements)

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“…This contrasts with pyruvate dehydrogenase complex deficiency [Shevell et al, 1994] and the A form of PC deficiency in which progressive microcephaly is observed [Atkin et al, 1979;Tsuchiyama et al, 1983]. The neuropathology of PC deficiency is similar to that of other mitochondrial diseases: spongiform degeneration, neuronal loss, gliosis, and delayed myelination can be found [Brown and Squier, 1996].…”

Section: Discussionmentioning

confidence: 86%

“…The neuropathology of PC deficiency is similar to that of other mitochondrial diseases: spongiform degeneration, neuronal loss, gliosis, and delayed myelination can be found [Brown and Squier, 1996]. Documentation of early developmental anomalies, i.e., alteration in the migration of cells with severe depletion of neurons in the cerebral cortex and numerous heterotopic neurons in the white matter, has so far been restricted to a single A form case report [Atkin et al, 1979]. These anomalies were not observed in either of our patients.…”

Section: Discussionmentioning

confidence: 94%

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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: 86%

Section: Discussionmentioning

confidence: 94%

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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“…Tissue heterogeneity would provide a convenient explanation for this patient's condition. However, Atkin et al (7,8) measured PC activity in liver, kidney, brain, cultured skin fibroblasts, and white blood cells of one patient and found it to be deficient in all tissues, suggesting that only one molecular form of PC exists in human tissues. Animal studies also confirm this observation (10).…”

Section: Discussionmentioning

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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“…The molecule, composed of four subunit chains of 185,000 molecular weight (1 l), binds irreversibly to the active form of proteases, changing the conformation of a2M and thereby trapping the enzyme (2). A similar conformational change can be mimicked by treatment…”

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confidence: 99%

“…Patients with less severe defects of this system have a much milder phenotype with intermittent ataxia and minimal lactic acidosis (23). Severe lactic acidosis is frequent in patients with pyruvate carboxylase deficiency (2,22,39,48) and mild to severe lactic acidosis is found in defects of the respiratory chain (14,25,26,(31)(32)(33)40,43,47,49).…”

mentioning

confidence: 99%

Lactic Acidosis and Mitochondrial Myopathy Associated with Deficiency of Several Components of Complex III of the Respiratory Chain

et al. 1984

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Pyruvate Carboxylase Deficiency and Lactic Acidosis in a Retarded Child without Leigh's Disease

Cited by 86 publications

References 13 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

Pyruvate Carboxylase Deficiency: A Benign Variant with Normal Development

Lactic Acidosis and Mitochondrial Myopathy Associated with Deficiency of Several Components of Complex III of the Respiratory Chain

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