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Título

INCLUSION BODY MYOPATHY AND FRONTOTEMPORAL DEMENTIA DUE TO VCP GENE MUTATION: CASE REPORT

RESUMO

CASE: A 51-years-old female presented with progressive muscular weakness for 10 years. She got worse from weakness in the past year and started complaining of forgetfulness, anomia and periphrases. She developed apraxia for daily activities, frequent falls and joint pain. Her sister was diagnosed with Paget’s disease of bone at age 20, and has language and behavioral changes. Her father died at advanced age with proximal weakness and behavioral changes without confirmed diagnosis. On physical examination, the patient was thin, bald and disoriented in time and place. There was wasting of trapezius and deltoid muscles, proximal quadriparesis (MRC IV), normal tonus and reflexes, abolished plantar responses, difficulty in arising from chair, waddling gait and brisk facial reflexes. Coordination and sensibility were normal. MMSE: 10 points (11 years/schooling), poor reading and figure interpretation, hesitant and reduced fluency, anomia, digital agnosia, acalculia, apathy, disinhibition and executive changes. Laboratory data showed normal CPK, aldolase and cardiological screening. EMG showed proximal myopathic pattern in all limbs; brain MRI demonstrated brain atrophy, mostly in left temporal lobe. In muscle biopsy, there was marked variability in fibers size, increased connective endomysial and perimysial tissue, endomysial inflammatory reaction, necrotic fibers and rimmed vacuoles. Immunohistochemistry was positive for CD4 and CD8. The Next-Generation Sequencing panel showed a pathogenic heterozygous mutation in exon 5 of VCP gene [c.463C>A; p.(Arg155Ser)], also present in her sister. Thus, it was consistent with inclusion body miositis (IBM) with frontotemporal dementia. DISCUSSION: The mutation on VCP gene (valosin containing protein) includes a group of hereditary diseases that can cause myopathy, frontotemporal dementia and bone disease, as well as others neurodegenerative diseases. It shares the same pathophysiology of protein aggregates with ubiquinin-proteossome system disfunction and autophagy. This hereditary type of IBM can be associated with the presence of inflammatory infiltrate in muscle biopsy, being the presence of rimmed vacuoles of great diagnostic contribution. FINAL COMMENTS: The recognition of the particularities of this multisystemic proteinopathy, a group of autosomal dominant diseases with variable penetrance and phenotypes, allow improving the treatment and follow-up of patients and promoting genetic guidance to their relatives.

Palavras Chave

Inclusion Body Myositis; Frontotemporal Dementia;Neurology