title: Mucolipidosis type IV: an update.
abstract: Mucolipidosis type IV (MLIV) is a neurodevelopmental as well as neurodegenerative disorder with severe psychomotor developmental delay, progressive visual impairment, and achlorydria. It is characterized by the presence of lysosomal inclusions in many cell types in patients. MLIV is an autosomal recessive disease caused by mutations in MCOLN1, which encodes for mucolipin-1, a member of the transient receptor potential (TRP) cation channel family. Although approximately 70-80% of patients identified are Ashkenazi Jewish, MLIV is a pan-ethnic disorder. Importantly, while MLIV is thought to be a rare disease, its frequency may be greater than currently appreciated, for its common presentation as a cerebral palsy-like encephalopathy can lead to misdiagnosis. Moreover, patients with milder variants are often not recognized as having MLIV. This review provides an update on the ethnic distribution, clinical manifestations, laboratory findings, methods of diagnosis, molecular genetics, differential diagnosis, and treatment of patients with MLIV. An enhanced awareness of the manifestations of this disorder may help to elucidate the true frequency and range of symptoms associated with MLIV, providing insight into the pathogenesis of this multi-system disease.
authors.affiliation: Section on Molecular Neurogenetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-3708, USA.
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Wakabayashi
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Gustafson
authors.forename: Ellen
authors.initials: E
authors.lastname: Sidransky
authors.forename: Ehud
authors.initials: E
authors.lastname: Goldin
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D003937:Diagnosis, Differential; D004331:Drosophila melanogaster; D005123:Eye / Q000473:pathology; D005755:Gastrins / Q000097:blood; D006801:Humans; D002479:Inclusion Bodies / Q000473:pathology; D007585:Jews; D051379:Mice; D023421:Models, Animal; D009081:Mucolipidoses / Q000175:diagnosis* / Q000208:ethnology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D009420:Nervous System / Q000473:pathology; D050051:Transient Receptor Potential Channels / Q000235:genetics*
chemical_list: D005755:Gastrins; C416674:MCOLN1 protein, human; D050051:Transient Receptor Potential Channels