Objective:Protein misfolding plays a central role not only in amyotrophic lateral sclerosis (ALS), but also in other conditions, such as frontotemporal dementia (FTD), inclusion body myopathy (hIBM) or Paget's disease of bone. The concept of multisystem proteinopathies (MSP) was created to account for those rare families that segregate at least 2 out of these 4 conditions in the same pedigree. The calcium-dependent phospholipid-binding protein annexin A11 was recently associated to ALS in European pedigrees. Herein, we describe in detail 3 Brazilian families presenting hIBM (isolated or in combination with ALS/FTD) caused by the novel p.D40Y change in the gene encoding annexin A11 (ANXA11). Methods: We collected clinical, genetic, pathological and skeletal muscle imaging from 11 affected subjects. Neuroimaging was also obtained from 8 patients and 8 matched controls. Results: Clinico-radiological phenotype of this novel hIBM reveals a slowly progressive predominant limb-girdle syndrome, but with frequent axial (ptosis/dropped head) and distal (medial gastrocnemius) involvement as well. Muscle pathology identified numerous rimmed vacuoles with positive annexin A11, TDP-43 and p62 inclusions, but no inflammation. Central nervous system was also involved: two patients had FTD, but diffusion tensor imaging uncovered multiple areas of cerebral white matter damage in the whole group (including the corticospinal tracts and frontal subcortical regions). Interpretation: These findings expand the phenotypic spectrum related to ANXA11. This gene should be considered the cause of a novel multisystem proteinopathy (MSP type 6), rather than just ALS.

Lupus erythematosus is a chronic autoimmune inflammatory disease of unknown cause that involves multiple systems. Autoimmune diseases that are prevalent in men usually manifest themselves clinically before the age of 50 years old and are characterized by an acute inflammation, whereas autoimmune diseases with predominance among women appear clinically in later stages of life, when chronic diseases, fibrosis and increased number of autoantibodies are present. Lupus erythematosus is more prevalent among women during the reproductive period, but the cause of this predilection is not fully established and little is known about the disease among men. We report a case of systemic lupus erythematosus (SLE) in a male patient whose diagnosis was delayed due to the systemic manifestations and because SLE is considered an uncommon disease in men.

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In the last few decades, there have been considerable improvements in the diagnosis and care of Duchenne muscular dystrophy (DMD), the most common childhood muscular dystrophy. International guidelines have been published and recently reviewed. A group of Brazilian experts has developed a standard of care based on a literature review with evidence-based graded recommendations in a two-part publication. Implementing best practice management has helped change the natural history of this chronic progressive disorder, in which the life expectancy for children of the male sex in the past used to be very limited. Since the previous publication, diagnosis, steroid treatment, rehabilitation, and systemic care have gained more significant insights with new original work in certain fields. Furthermore, the development of new drugs is ongoing, and some interventions have been approved for use in certain countries. Therefore, we have identified the need to review the previous care recommendations for Brazilian patients with DMD. Our objective was to create an evidence-based document that is an update on our previous consensus on those topics.

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