Spectrum of movement disorders and neurotransmitter abnormalities in paediatric POLG disease

J Inherit Metab Dis. 2018 Nov;41(6):1275-1283. doi: 10.1007/s10545-018-0227-7. Epub 2018 Aug 30.

Abstract

Objectives: To describe the spectrum of movement disorders and cerebrospinal fluid (CSF) neurotransmitter profiles in paediatric patients with POLG disease.

Methods: We identified children with genetically confirmed POLG disease, in whom CSF neurotransmitter analysis had been undertaken. Clinical data were collected retrospectively. CSF neurotransmitter levels were compared to both standardised age-related reference ranges and to non-POLG patients presenting with status epilepticus.

Results: Forty-one patients with POLG disease were identified. Almost 50% of the patients had documented evidence of a movement disorder, including non-epileptic myoclonus, choreoathetosis and ataxia. CSF neurotransmitter analysis was undertaken in 15 cases and abnormalities were seen in the majority (87%) of cases tested. In many patients, distinctive patterns were evident, including raised neopterin, homovanillic acid and 5-hydroxyindoleacetic acid levels.

Conclusions: Children with POLG mutations can manifest with a wide spectrum of abnormal movements, which are often prominent features of the clinical syndrome. Underlying pathophysiology is probably multifactorial, and aberrant monoamine metabolism is likely to play a role.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • DNA Polymerase gamma / genetics
  • Female
  • Homovanillic Acid / cerebrospinal fluid
  • Humans
  • Hydroxyindoleacetic Acid / cerebrospinal fluid
  • Infant
  • Male
  • Mitochondrial Diseases / cerebrospinal fluid*
  • Mitochondrial Diseases / genetics
  • Movement Disorders / etiology*
  • Mutation
  • Neopterin / cerebrospinal fluid
  • Neurotransmitter Agents / cerebrospinal fluid*
  • Retrospective Studies

Substances

  • Neurotransmitter Agents
  • Hydroxyindoleacetic Acid
  • Neopterin
  • DNA Polymerase gamma
  • POLG protein, human
  • Homovanillic Acid