Dados do Trabalho

Título

A case of adult-onset leukodystrophy of rare underlying aetiology: the importance of expanding tools for earlier diagnosis.

RESUMO

CASE REPORT: A 43-year-old male developed dementia in the previous three years. He presented with dysarthria, dysphasia, speech and ideomotor apraxia and, mainly, gait apraxia, which was followed by knee walking. On examination there was paratonia, global hyperreflexia despite preserved strength. MRI disclosed diffuse cortical atrophy with unspecific bilateral white matter hypersignal, suggestive of advanced leukodystrophy (LKD). Electroneuromyography was unremarkable, as well as, infectious and metabolic screening. CSF revealed hyperproteinorrachia. Genetic investigation from salivary sample identified one likely pathogenic mutation in ETFDH gene, associated to autosomal recessive multiple-acyl-CoA dehydrogenase deficiency (MADD). Dietary orientation and supplementation with riboflavin were initiated.DISCUSSION: MADD impairs the riboflavin-dependent electron transfer system in mitochondria. This genetic mutation compromises the fatty acid oxidation, particularly branched chain ones, and the amino acids metabolism. Therefore, treatment recommendations include: protein and fat-restricted diet every 4 h; conjugation of toxic metabolites with L-carnitine and glycine reposition; supplementation with riboflavin; besides the promising replacement of endogenous ketone body with sodium D,L-3-hydroxybutyrate Clinical spectrum varies widely depending on the degree of hypoketotic hypoglycaemia, metabolic acidosis and defective protein metabolism. It ranges from lethal malformation to adult onset, throughout a myriad of complications: hepatic dysfunction, cardio/myopathy, neurodevelopmental delay and LKD. In late-onset MADD, it is more prominent the neuromuscular phenotypes, with demyelination directed to peripheral nervous system. On the other hand, LKD in adults shelters others inherited and acquired disorders (e.g.vascular, toxic, degenerative or inflammatory) without precise genotype–phenotype correlation. Symmetrical pyramidal findings and varying degrees of cognitive impairment are common. FINAL COMENTS:Adult-onset LKD requires a puzzling investigation, considering the differential diagnosis of the underlying pathology. The prevalence is lower than in childhood and specific radiological/clinical markers may be missing. Our case illustrates MADD leading to adult-onset LKD, while it would be expected milder findings at this age. Expanding the access to ancillary exams might widen the etiological panel for young-onset dementia and guide therapeutical interventions.