The 7 reported patients had variable clinical presentations:
• Early onset with rapid deterioration – rapid neonatal metabolic decompensation with severe lactic acidosis, hypoglycaemia, neurological impairment, liver failure and death at 1 month of age
• Severe progressive phenotype – progressive epileptic encephalopathy with myoclonic jerks, psychomotor regression, vomiting, ptosis and fluctuating ophthalmoparesis leading to death at 17 months of age
• Milder and slowly progressive phenotype – patients were ambulatory with slowly progressive developmental delay, autism spectrum disorder, mild intellectual disability or non-specific mild developmental delay, ataxia, optic atrophy and fluctuating proximal muscle weakness, ophthalmoparesis and epilepsy.
Main clinical features included:
• Neurological: seizures (3/7), intellectual disability (4/7), speech delay (3/7), tremor (1/7), hypertonia (1/7), axial hypotonia (1/7) hypotonia (1/7), fatigue (1/7)
• Ophthalmological: nystagmus (3/7), bilateral optic atrophy (1/7), squint (2/7)
• Neuromuscular: ptosis (3/7), hypotinia (1/7), fatigable weakness (2/7)
• Hepatic: Acute liver failure in neonatal period (1/7)
• Respiratory: respiratory distress in neonatal period (1/7)
• GI: failure to thrive (1/7)
• Behaviour: autism spectrum disorder (1/7), aggressive behavour (1/7), hyperactivity (2/7)
Investigations:
• Labs: raised Creatine Kinase (1/7), raised lactate (3/7)
• Investigations: Brain MRI normal in 2/7, and mild non-specific changes in 5/7. Non specific brain MRI changes included: microcephaly (1/7), white matter lesions (1/7), lactate peak (1/7), loss of white matter and cortical atrophy (1/7), cerebral atrophy (2/7), demyelination (2/7) and thin corpus callosum (2/7).
• Muscle biopsy: SDH hyper-reactivity and COX negative fibres (3/7), combined defect in the activities of OXPHOS enzyme complexes I and IV (3/7)
TEFM