RESUMO
Genetic abnormalities in mitochondrial complex assembling factors are associated with leukoencephalopathy. We present a 1-year-old girl with consciousness disturbance after a respiratory infection. Brain MRI revealed leukoencephalopathy with bilaterally symmetrical hyperintensity in the substantia nigra, medial thalamic nuclei, and basal nuclei, as well as cavities in the cerebral white matter and corpus callosum. Lactate levels in the spinal fluid were high, while magnetic resonance spectroscopy of the cerebral white matter and basal nuclei showed high peak lactate levels, suggesting mitochondrial dysfunction. The respiratory enzyme activity of complex I was reduced to 17% to 21% in skeletal muscle. Whole exome sequencing identified compound heterozygous variations in NDUFAF3, involved in the assembly of mitochondrial complex I (c.342_343insGTG:p.117Valdup, c.505C > A:p.Pro169Thr). Two-dimensional, blue-native polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate-PAGE revealed reductions in Q-module (NDUFS2, NDUFS3, and NDUFA9) and P-module (NDUFB10 and NDUFB11) subunits, indicating disruption of mitochondrial complex I assembly. Our report expands the spectrum of clinical phenotypes associated with pathogenic variants of NDUFAF3.
Assuntos
Predisposição Genética para Doença , Leucoencefalopatias/genética , Mitocôndrias/genética , Proteínas Mitocondriais/genética , Complexo I de Transporte de Elétrons/genética , Feminino , Humanos , Lactente , Leucoencefalopatias/patologia , Mitocôndrias/patologia , Mutação , Sequenciamento do ExomaAssuntos
Deleção Cromossômica , Cromossomos Humanos Par 2 , Doença de Hirschsprung/diagnóstico , Doença de Hirschsprung/genética , Proteínas de Homeodomínio/genética , Mutação , Proteínas Repressoras/genética , Adulto , Criança , Pré-Escolar , Quebra Cromossômica , Anormalidades Craniofaciais/diagnóstico , Anormalidades Craniofaciais/genética , Análise Mutacional de DNA , Feminino , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Masculino , Microcefalia/diagnóstico , Microcefalia/genética , Síndrome , Homeobox 2 de Ligação a E-box com Dedos de ZincoRESUMO
Primary erythermalgia is a rare neuropathy characterized by attacks of burning pain and redness in the extremities in response to warm stimuli. We describe here a boy with erythermalgia whose painful attacks began in infancy. We found a novel mutation of SCN9A, which is a responsible gene for primary erythermalgia in this case. In his teens, he developed wintry hypothermia with resultant neurological dysfunction and recurrent pneumonia. During the course of pneumonia, he had transient encephalopaty with a reversible lesion in the splenium of the corpus callosum. In addition to excessive cooling, a defect in central thermoregulation may have caused hypothermia in this patient.