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

Am J Med Genet. 1999 May 21;84(2):94-101.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / blood supply*
  • Female
  • Humans
  • Infant, Newborn
  • Ischemia / diagnosis*
  • Liver / abnormalities
  • Liver / pathology
  • Male
  • Muscle, Skeletal / abnormalities
  • Muscle, Skeletal / anatomy & histology
  • Pregnancy
  • Pyruvate Carboxylase Deficiency Disease / diagnosis*
  • Pyruvate Carboxylase Deficiency Disease / genetics
  • Ultrasonography, Prenatal*