LAUSR

Following a mild head trauma 1 week prior, a 6-year-old girl diagnosed with Leigh syndrome was admitted to our Child Neurology Department due to a loss of reaction to external stimuli and swallowing dysfunction. She was able to walk and began to speak at 30 months of age, but then lost the ability to walk at 5 years old, so she had delays and regressions in development. The previous year, the patient was hospitalized due to acute diarrhea, severe lactic acidosis, and encephalopathy. Plasma ammonia level was normal and she recovered with hydration and bicarbonate replacements. Urine organic acids during this metabolic crisis showed elevated ethylmalonic acid levels (96 mmol/mol/crea; reference range 0–15). The physical examination revealed axial hypotonia, muscle weakness, lower limb spasticity, increased deep tendon reflexes, extensor bilateral plantar reflexes, and clonus. The ophthalmic examination identified bilateral tortuosity in retinal veins. Biochemical blood tests showed mildly elevated plasma lactate and C4-acylcarnitine levels, while serum pyruvate, ammonia, amino acids, and creatine kinase levels were normal. Blood tandem mass spectrometry was normal, but urine organic acid examination revealed a 1.2-fold increase in ethylmalonic acid levels. The electroencephalography record demonstrated diffuse encephalopathy. The electromyography was normal. The brain MRI revealed bilateral hyperintensity in the head of the caudate nucleus, subcortical and deep white matter, and cerebellar white matter. It also showed multiple cavitation foci; diffusion-weighted MRI showed diffusion-restricting lesions. Computerized tomography of the cranium showed calcification of the posterior occipital area (Figs. 1, 2). Genetic tests showed a pathogenic, homozygous, c.3G>T (p.Met1Ile) mutation (rs119103249) in the first codon of ETHE1 gene. Ethylmalonic encephalopathy (EE) is caused by mutations in the ETHE1 gene, which codes a mitochondrial sulfur dioxygenase. Accumulation of hydrogen sulfide is attributable to loss-of-function mutations of ETHE1 gene. Therefore, elevated levels of hydrogen sulfide are responsible for the inhibition of cytochrome c oxidase and degradation of short-chain acyl CoA dehydrogenase subunits in the colonic mucosa, muscle, and brain. Vascular lesions in the skin and other organs are observed due to vasoactive and vasotoxic effects [1]. In the literature, multiple cavitations in relation to EE have been reported as rare. Pigeon et al. reported monochorionic twins diagnosed with EE who had neuroimaging changes affecting the white matter, corpus callosum, and basal ganglia as leukoencephalopathy and cavitation [2]. According to the MRI findings of leukoencephalopathy and multiple cavitations, differential diagnosis should consider diseases related to nuclear mitochondrial defects and the spectrum of white matter lesions in OXPHOS (oxidative phosphorylation)-related disorders, for example, mutations in NDUFS1 with isolated complex I deficiency associated with progressive cavitating leukoencephalopathy (PCL), mutations in LYRM7 with the defect of * Nihal Olgac Dundar [email protected]