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Here, we describe two patients from two independent families presenting with progressive psychomotor regression, delayed myelination, brain atrophy, neutropenia, skeletal abnormalities, and mucopolysaccharidosis\u2010like dysmorphic features. Both patients were homozygous for the same intronic variant in\n                    <jats:italic>VPS16<\/jats:italic>\n                    , a gene encoding a subunit of the HOPS and CORVET complexes. The variant impaired normal mRNA splicing and led to an ~85% reduction in VPS16 protein levels in patient\u2010derived fibroblasts. Levels of other HOPS\/CORVET subunits, including VPS33A, were similarly reduced, but restored upon re\u2010expression of VPS16. Patient\u2010derived fibroblasts showed defects in the uptake and endosomal trafficking of transferrin as well as accumulation of autophagosomes and lysosomal compartments. Re\u2010expression of VPS16 rescued the cellular phenotypes. Zebrafish with disrupted\n                    <jats:italic>vps16<\/jats:italic>\n                    expression showed impaired development, reduced myelination, and a similar accumulation of lysosomes and autophagosomes in the brain, particularly in glia cells. This disorder resembles previously reported patients with mutations in\n                    <jats:italic>VPS33A<\/jats:italic>\n                    , thus expanding the family of mucopolysaccharidosis\u2010like diseases that result from mutations in HOPS\/CORVET subunits.\n                  <\/jats:p>","DOI":"10.15252\/emmm.202013376","type":"journal-article","created":{"date-parts":[[2021,5,3]],"date-time":"2021-05-03T06:35:33Z","timestamp":1620023733000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Bi\u2010allelic VPS16 variants limit HOPS\/CORVET levels and cause a mucopolysaccharidosis\u2010like disease"],"prefix":"10.1038","volume":"13","author":[{"given":"Kalliopi","family":"Sofou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kolja","family":"Meier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie E","family":"Sanderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debora","family":"Kaminski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laia","family":"Montoliu\u2010Gaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Samuelsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Blomqvist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lotta","family":"Agholme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jutta","family":"G\u00e4rtner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"M\u00fchlhausen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklas","family":"Darin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1231-1562","authenticated-orcid":false,"given":"Tahsin Stefan","family":"Barakat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Schlotawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2175-8713","authenticated-orcid":false,"given":"Tjakko","family":"van Ham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Asin Cayuela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8881-0523","authenticated-orcid":false,"given":"Fredrik H","family":"Sterky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,3]]},"reference":[{"key":"BFEMMM202013376_CR1","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.neuron.2017.01.018","volume":"93","author":"E Aflaki","year":"2017","unstructured":"Aflaki E, Westbroek W, Sidransky E (2017) The complicated relationship between gaucher disease and parkinsonism: insights from a rare disease. 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