Infantile parkinsonism and GABAergic hypotransmission in a patient with pyruvate carboxylase deficiency

Gene. 2013 Dec 15;532(2):302-6. doi: 10.1016/j.gene.2013.08.036. Epub 2013 Aug 23.

Abstract

Pyruvate carboxylase deficiency is a rare metabolic disorder, with three different phenotypes. We aim to report the case of a newborn presenting the severe neonatal form of this deficiency (the B or "French" phenotype, hypokinesia and rigidity being the main features) and the results of the study of classic neurotransmitters involved in movement control. Hyperdopaminergic transmission (both in the cerebrospinal fluid and in the substantia nigra) and hypoGABAergic transmission (in the substantia nigra) were found. Both gamma-aminobutyric acid and dopamine markers were found coexisting in individual neurons of the substantia nigra. This is the first time this phenomenon has been reported in the literature. We discuss the possible role of GABAergic deficiency, its interaction with other neurotransmitters and its implication in neurotransmitter homeostasis. A better comprehension of that field would increase understanding of the pathophysiology of neurological symptoms and neurotransmitter plasticity.

Keywords: CSF; Cerebrospinal fluid; Dopamine; GABA; GAD; Infantile Parkinsonism; MRI; MRS; Neurotransmitters; PC; Pyruvate carboxylase; SN; SPNs; STN; cerebrospinal fluid; gamma-aminobutyric acid; glutamate decarboxylase; magnetic resonance image; magnetic resonance spectroscopy; pyruvate carboxylase; spiny projection neurons; substantia nigra; subthalamic nucleus.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / metabolism
  • Brain / pathology
  • Fatal Outcome
  • Female
  • GABAergic Neurons / physiology
  • Humans
  • Parkinsonian Disorders / diagnosis*
  • Parkinsonian Disorders / enzymology
  • Parkinsonian Disorders / physiopathology
  • Pyruvate Carboxylase Deficiency Disease / diagnosis*
  • Pyruvate Carboxylase Deficiency Disease / physiopathology
  • Synaptic Transmission
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Tyrosine 3-Monooxygenase