Mimics and chameleons in mitochondrial pathology
2Morozov's Moscow City Child Clinical Hospital, Russia
3Russian children clinical hospital, Russia
Background: Primary mitochondrial diseases (PMD) arise as a result of the mitochondrial respiratory chain dysfunction and are characterised by clinical and genetic heterogeneity; the clinical features of PMD overlap with common neurological and non-neurological diseases. Vice versa, some non-mitochondrial pathologies may resemble PMD - this presents a diagnostic challenge. Here we describe both “mimics”— conditions that may clinically resemble PMD and “chameleons” — mitochondrial disorders, that may look like something else.
Methods: By whole exome sequencing (WES) we screened DNA of 10 pediatric patients suspected for inherited disoders.
Results: A 1-year-old girl with subacute necrotizing encephalopathy, PEO, hyperkinesis, spastic tetraparesis and slightly elevated lactate had symmetrical lesions in the nuclei of the globus pallidus on brain MRI; level of urine organic acids and acylcarnitine was normal. The girl was suspected for PMD, however WES has revealed two pathogenic variants in GCDH gene. The patient turned out to be a low excretor of glutaric acid. Two 5-month-old sibs were suspected for Leigh-like syndrome based on brain MRI data, developmental delay and symptomatic focal epilepsy; on WES we have detected a homozygous nonsense mutation in the ST3GAL3 gene.
3 female patients had similar clinical presentation: manifestation at 12-14 months with polyneuropathy, myoclonus, total ophthalmoparesis, cognitive impairment. Despite of clinical diagnosis of Niemann-Pick C disease, we have detected pathogenic mutations in the TWNK gene. Molecular analysis of 4 patients, initially suspected for spinal muscular atrophy (bell-shaped chest deformity, "frog-leg" posture), has showed up pathogenic variants in SCO2 gene.
Conclusion:The reported cohort highlights that many genetic conditions may mimic each other.
Next Generation Sequencing has revolutionized the diagnostic screening for such complicated disorders and helped to shorten the diagnostic odyssey for many patients.
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