The biochemical basis of the behavioral disorder in the Lesch-Nyhan syndrome

Neurosci Biobehav Rev. 1985 Summer;9(2):169-78. doi: 10.1016/0149-7634(85)90043-0.

Abstract

An inherited complete deficiency of hypoxanthine-guanine phosphoribosyltransferase in male children is associated with a severe neurological disorder characterized by chloroform and athetoid movements, hypertonicity, mental retardation, and self-injurious behavior. In the review that follows several possible mechanisms by which the enzyme defect may cause the CNS disorder are discussed. Current evidence suggests that the primary neural deficit in the Lesch-Nyhan syndrome is a deficiency of dopamine in the basal ganglia. It is argued that this neurochemical lesion results from a deficiency of purine nucleotides which impairs arborization of nigrostriatal neurons during perinatal development. Differences in the ontogenetic timing of the neurochemical lesion may be partly responsible for the different neurological symptoms displayed by persons afflicted with the Lesch-Nyhan and Parkinson's syndromes.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adenine Nucleotides / metabolism
  • Animals
  • Central Nervous System / embryology
  • Central Nervous System / growth & development
  • Central Nervous System / metabolism*
  • Child
  • Child, Preschool
  • Clonidine
  • Corpus Striatum / metabolism
  • Disease Models, Animal
  • Dopamine / metabolism
  • Humans
  • Hydroxydopamines / pharmacology
  • Infant
  • Infant, Newborn
  • Lesch-Nyhan Syndrome / metabolism*
  • Morphogenesis
  • Norepinephrine / metabolism
  • Oxidopamine
  • Parkinson Disease / physiopathology
  • Purine Nucleotides / deficiency
  • Purines / metabolism
  • Rats
  • Self Mutilation / chemically induced
  • Self Mutilation / metabolism*
  • Serotonin / metabolism
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Adenine Nucleotides
  • Hydroxydopamines
  • Purine Nucleotides
  • Purines
  • Serotonin
  • gamma-Aminobutyric Acid
  • Oxidopamine
  • Clonidine
  • Dopamine
  • Norepinephrine