Investigations and Management of Rare Treatable Neurological Disorders
1. AR-GCH1 Deficiency Without Hyperphenylalaninaemia
- Presentation: Resembles cerebral palsy, oculogyric crises, tremulousness, bradykinesia.
- Key Investigations:
- Phenylalanine loading test: Elevated blood spot phenylalanine and phenylalanine/tyrosine ratio.
- CSF pterins low; monoamine neurotransmitters may be normal.
- Definitive: Peripheral blood mononuclear or fibroblast GTP cyclohydrolase enzyme assay or mutation analysis.
2. ACTH Unresponsiveness
- Presentation: Recurrent encephalopathy, hypoglycemia, epilepsy, subtle joint hyperpigmentation.
- Key Investigations: ↓ Glucose, ↓ Cortisol, ↑ ACTH.
- Treatment: Cortisol replacement therapy.
3. Biotinidase Deficiency
- Presentation: Epilepsy, developmental delay, neurological deficits, mimics Leigh syndrome ± alopecia, rash.
- Key Investigations:
- Brain/spinal cord MRI, urine organic acids.
- Blood lactate, biotinidase activity assay.
4. Biotin-Responsive Basal Ganglia Disease
- Presentation: Rapid motor skill loss, quadriparesis, seizures, akinetic mutism.
- Key Investigations:
- Brain MRI: Caudate and putamen necrosis.
- Mutation in SLC19A3 gene.
