Dopa-responsive akinesia: Homozygous GCH1 mutation (P5.150)

Topic: Brain proteins, microglia and lab models

This individual had childhood-onset progressive motor impairment. Examination at age 13 years revealed profound, generalized akinesia without rigidity or dystonia. Voluntary movements were limited to swallowing, blinking, and eye movements. Neuroimaging and laboratory studies including serum amino acids were normal. Genetic testing revealed homozygous GCH1 mutation c.626C>G, a novel homozygous mutation that disturbs interspecies conserved residue (pThr209Arg ). Low dose levodopa-carbiodopa administration provided immediate, sustained, and profound benefit. With levodopa-carbidopa and 5-hydroxytryptophan administration and physical and occupational therapy, she is able to walk (9 months following treatment initiation), run, dance, speak, attend school, write and perform all activities of daily living. Akinesia without rigidity has not been described in subjects with GCH1 mutation. This report extends the clinical spectrum of GCH1 mutations and other dopa-responsive syndromes and permits greater recognition of this treatable disorder.

@article{lineback2016-a0ddd430,
  author  = {Lineback, Christina M. and Jensen, Kristin Manteuffel and Wilcock, Sandra and Fink, John K.},
  title   = {{Dopa-responsive akinesia: Homozygous GCH1 mutation (P5.150)}},
  journal = {Neurology},
  year    = {2016},
  doi     = {10.1212/wnl.86.16_supplement.p5.150},
  url     = {https://doi.org/10.1212/wnl.86.16_supplement.p5.150}
}

Key findings

• This individual had childhood-onset progressive motor impairment.
• Examination at age 13 years revealed profound, generalized akinesia without rigidity or dystonia.
• Voluntary movements were limited to swallowing, blinking, and eye movements.
• Neuroimaging and laboratory studies including serum amino acids were normal.
• Genetic testing revealed homozygous GCH1 mutation c.626C>G, a novel homozygous mutation that disturbs interspecies conserved residue (pThr209Arg ).

Why it matters

This case report describes one person with a GCH1 mutation and childhood-onset movement problems who improved greatly with levodopa-carbidopa and other therapy. It concerns a rare dopa-responsive movement disorder, not Alzheimer's disease, and reports a single individual.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1212/wnl.86.16_supplement.p5.150
• Original source →

May need a subscription OpenAlex found no free copy of the full text (checked 6 Feb 1020), so the publisher may charge for it.

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