LIMB GIRDLE MUSCULAR DYSTROPHIES: P.167TRAPPC11-opathies: an emerging phenotype of muscle-eye-brain-liver

Abstract

Transport protein particle complex (TRAPPC) is involved in endoplasmic reticulum to Golgi transportation. In humans, TRAPPC11 protein is a part of the complex III and its mutations are associated with problems in trafficking of protein to the cell membrane with secretory deficits and its defects can inhibit of glycosylation of alpha-DG. Disorders linked to mutations of proteins of TRAPPC have recentlybeen called TRAPPopathies. TRAPPC11 mutations have been associated and limb-girdle muscular dystrophy (LGMD), congenital muscular dystrophy (CMD) and hepatomegaly with steatosis and ocular involvement (alacrima, catharatas). We described 4 patients with congenital microcephaly, strabismus, moderate to mild proximal weakness, hyperckemia, hypertransaminemia, movement disorders (hyperkinesia, stereotypia, chorea, athetosis) and increase neurological impairment after of infectious insult. Three of them are gipsy. All had intellectual disability. Two patients suffered epilepsy. Muscle biopsy showed reduction of alpha dystroglycan inmunofluorescence. Exome sequencing of majory patients identified homozygous mutation (c.1287+5G>A) in TRAPPC11 gene. One of them had a compound heterozygous mutation in TRAPPC11 gene, one of them was the previously described (c.1287 +5G>A) and the second mutation (c.3379_3380insT) has not been reported before. TRAPPC11-opathies should be considered in the diagnosis of children with proximal weakness, hypotonia, hyperckemia and extramuscular manifestations such as cognitive impairment, epilepsy, movement disorders, eye and liver involvement. We concluded that TRAPPC11-opathies have a phenotype that can be called "phenotype muscle-eye-brain-liver". Interestingly, all of our cases had an increase in neurological affections after an infectious insult indicating that TRAPPC11 plays a physiological role in multiple systems in humans including metabolic system.