Subject 2 is the first son of healthy second-cousin Kurdish parents, who have a healthy younger daughter. He was born by normal vaginal delivery at 36 weeks of gestation (birth weight = 2.8 kg [50th percentile]) after an uneventful pregnancy. He spoke his first words at 12 months and at 16 months was walking independently. By 2 years, his parents noted a general physical weakness, and at 25 months, shortly after an unexplained fever, his gait deteriorated. Further motor regression and rapid onset of spasticity of all four limbs followed. He developed swallowing difficulties and required a gastrostomy tube for feeding. At 2.5 years, he was bedridden and was unable to walk, grasp, or speak. He showed some recovery over subsequent months, during which he regained several words, and by 3 years was walking with assistance. Although there have been no further episodes of rapid regression, he has slowly deteriorated and has displayed dysarthric speech and wheelchair dependency from 7 years of age. Over the last 2 years, he has lost all voluntary movement in his limbs. Speech is just about understandable, and cognitive abilities remain good, but his mood is very low. He has an implanted pump for intrathecal Baclofen therapy and receives Botox injections every 3 months. Vison is impaired as a result of optic atrophy, whereas hearing is normal. Routine laboratory investigations revealed normal lactate levels in blood (1.2 mmol/L; normal < 2.2 mmol/L) and cerebrospinal fluid (CSF) (1.8 mmol/L; normal < 2.4 mmol/L). Light microscopy and routine histology of skeletal muscle biopsy did not exhibit any specific findings. Initial cranial MRI showed extensive and progressive disseminating lesions in supratentorial white-matter regions, including U-fibers and the corpus callosum, in the basal ganglia, brainstem, and cervical spinal cord, some of which enhanced with contrast (Figure 1C). Magnetic resonance spectroscopy revealed elevated lactate in multiple areas. On follow-up MRI, the brain abnormalities were less swollen, did not enhance, and displayed partial cystic degeneration and white-matter volume loss (Figure 1D).