{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:44:09Z","timestamp":1771461849384,"version":"3.50.1"},"reference-count":22,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T00:00:00Z","timestamp":1646006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Mucopolysaccharidosis-plus syndrome (MPS-PS) is a novel autosomal recessive disorder caused by a mutation in the VPS33A gene. This syndrome presents with typical symptoms of mucopolysaccharidosis, as well as congenital heart defects, renal, and hematopoietic system disorders. To date, twenty-four patients have been described. There is no specific therapy for MPS-PS; clinical management is therefore limited to symptoms management. The clinical course is rapidly progressive, and most patients die before 1\u20132 years of age. We describe a currently 6-year-old male patient with MPS-PS presenting with multiorgan involvement. Symptoms started at four months of age when he progressively suffered from numerous acute and potentially life-threatening events. When he was two years old, he developed secondary hemophagocytic lymphohistiocytosis (HLH), which was successfully treated with steroids. To date, this child represents the oldest patient affected by MPS-PS described in the literature and the first one presenting with a life-threatening secondary HLH. The prolonged steroid treatment allowed a stabilization of his general and hematological conditions and probably determined an improvement of his psychomotor milestones and new neurological acquisitions with an improvement of quality of life. HLH should be suspected and adequately treated in MPS-PS patients presenting with suggestive symptoms of the disease. The usefulness of a prolonged steroid treatment to improve the clinical course of children with MPS-PS deserves further investigation.<\/jats:p>","DOI":"10.3390\/genes13030442","type":"journal-article","created":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T20:09:57Z","timestamp":1646078997000},"page":"442","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Mucopolysaccharidosis-Plus Syndrome, a Rapidly Progressive Disease: Favorable Impact of a Very Prolonged Steroid Treatment on the Clinical Course in a Child"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3426-2749","authenticated-orcid":false,"given":"Martha Caterina","family":"Faraguna","sequence":"first","affiliation":[{"name":"Universit\u00e0 degli Studi Milano-Bicocca, 20100 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Musto","sequence":"additional","affiliation":[{"name":"Universit\u00e0 degli Studi Milano-Bicocca, 20100 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viola","family":"Crescitelli","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Universit\u00e0 degli Studi Milano-Bicocca, Fondazione MBBM, San Gerardo Hospital, Via Pergolesi 33, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4707-212X","authenticated-orcid":false,"given":"Maria","family":"Iascone","sequence":"additional","affiliation":[{"name":"Laboratory of Genetic Medicine, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigina","family":"Spaccini","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit, Department of Obstetrics and Gynecology, V. Buzzi Children\u2019s Hospital, University of Milan, 20100 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9371-7454","authenticated-orcid":false,"given":"Davide","family":"Tonduti","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit, V. Buzzi Children\u2019s Hospital, 20100 Milan, Italy"},{"name":"C.O.A.L.A (Center for Diagnosis and Treatment of Leukodystrophies), V. Buzzi Children\u2019s Hospital, 20100 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiziana","family":"Fedeli","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, FMBBM, San Gerardo Hospital, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gaia","family":"Kullmann","sequence":"additional","affiliation":[{"name":"Child Neuropsychiatrist Unit, San Gerardo Hospital, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Canonico","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Universit\u00e0 degli Studi Milano Bicocca, San Gerardo Hospital, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6933-6723","authenticated-orcid":false,"given":"Alessandro","family":"Cattoni","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Universit\u00e0 degli Studi Milano-Bicocca, Fondazione MBBM, San Gerardo Hospital, Via Pergolesi 33, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabiola","family":"Dell\u2019Acqua","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Universit\u00e0 degli Studi Milano-Bicocca, Fondazione MBBM, San Gerardo Hospital, Via Pergolesi 33, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4828-3893","authenticated-orcid":false,"given":"Carmelo","family":"Rizzari","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Universit\u00e0 degli Studi Milano-Bicocca, Fondazione MBBM, San Gerardo Hospital, Via Pergolesi 33, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8743-4407","authenticated-orcid":false,"given":"Serena","family":"Gasperini","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Universit\u00e0 degli Studi Milano-Bicocca, Fondazione MBBM, San Gerardo Hospital, Via Pergolesi 33, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"476","DOI":"10.21037\/atm.2018.11.39","article-title":"Lysosomal storage disease overview","volume":"6","author":"Sun","year":"2018","journal-title":"Ann. Transl. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1001\/jama.281.3.249","article-title":"Prevalence of Lysosomal Storage Disorders","volume":"281","author":"Meikle","year":"1999","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41572-018-0025-4","article-title":"Lysosomal storage diseases","volume":"4","author":"Platt","year":"2018","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.rchipe.2015.10.004","article-title":"Mucopolisacaridosis: Caracter\u00edsticas cl\u00ednicas, diagn\u00f3stico y de manejo","volume":"87","author":"Higuera","year":"2016","journal-title":"Rev. Chil. Pediatr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.ymgme.2017.12.434","article-title":"Gene therapy for Mucopolysaccharidoses","volume":"123","author":"Sawamoto","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1056\/NEJMoa2106596","article-title":"Hematopoietic Stem- and Progenitor-Cell Gene Therapy for Hurler Syndrome","volume":"385","author":"Gentner","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Vasilev, F., Sukhomyasova, A., and Otomo, T. (2020). Mucopolysaccharidosis-Plus Syndrome. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21020421"},{"key":"ref_8","first-page":"173","article-title":"Mutation inVPS33Aaffects metabolism of glycosaminoglycans: A new type of mucopolysaccharidosis with severe systemic symptoms","volume":"26","author":"Kondo","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2514","DOI":"10.1093\/hmg\/ddz077","article-title":"The lysosomal disease caused by mutant VPS33A","volume":"28","author":"Pavlova","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/MCD.0000000000000149","article-title":"A probable new syndrome with the storage disease phenotype caused by the VPS33A gene mutation","volume":"26","author":"Dursun","year":"2017","journal-title":"Clin. Dysmorphol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1023\/B:RUGE.0000048669.22362.1c","article-title":"The Structure and Diversity of Hereditary Pathology in Sakha Republic (Yakutia)","volume":"40","author":"Tarskaia","year":"2004","journal-title":"Russ. J. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1136\/jmg.2007.051979","article-title":"Clinical, molecular and histopathological features of short stature syndrome with novel CUL7 mutation in Yakuts: New population isolate in Asia","volume":"44","author":"Maksimova","year":"2007","journal-title":"J. Med. Genet."},{"key":"ref_13","first-page":"334","article-title":"Investigating the effects of prehistoric migrations in Siberia: Genetic variation and the origins of Yakuts","volume":"120","author":"Pakendorf","year":"2006","journal-title":"Qual. Life Res."},{"key":"ref_14","first-page":"1244","article-title":"Gene pools of peoples from the Republic of Sakha (Yakutiia): Structure, origin, genetic relationships","volume":"46","author":"Fedorova","year":"2010","journal-title":"Genetika"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.1111\/febs.12151","article-title":"Tethering complexes in the endocytic pathway: CORVET and HOPS","volume":"280","author":"Solinger","year":"2013","journal-title":"FEBS J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1091\/mbc.3.12.1389","article-title":"Morphological classification of the yeast vacuolar protein sorting mutants: Evidence for a prevacuolar compartment in class E vps mutants","volume":"3","author":"Raymond","year":"1992","journal-title":"Mol. Biol. Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.beem.2014.10.001","article-title":"Metachromatic leukodystrophy: Disease spectrum and approaches for treatment","volume":"29","author":"Boelens","year":"2015","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Schlotawa, L., Adang, L.A., Radhakrishnan, K., and Ahrens-Nicklas, R.C. (2020). Multiple Sulfatase Deficiency: A Disease Comprising Mucopolysaccharidosis, Sphingolipidosis, and More Caused by a Defect in Posttranslational Modification. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103448"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"20423","DOI":"10.1074\/jbc.R110.134452","article-title":"Common and Uncommon Pathogenic Cascades in Lysosomal Storage Diseases","volume":"285","author":"Vitner","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1089\/ars.2010.3485","article-title":"Autophagy Shapes Inflammation","volume":"14","author":"Petrovski","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1093\/brain\/awg089","article-title":"Central nervous system inflammation is a hallmark of pathogenesis in mouse models of GM1 and GM2 gangliosidosis","volume":"126","author":"Jeyakumar","year":"2003","journal-title":"Brain"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.jpeds.2013.03.002","article-title":"B-Cell Depletion and Immunomodulation before Initiation of Enzyme Replacement Therapy Blocks the Immune Response to Acid Alpha-Glucosidase in Infantile-Onset Pompe Disease","volume":"163","author":"Elder","year":"2013","journal-title":"J. Pediatr."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/3\/442\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:29:08Z","timestamp":1760135348000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/3\/442"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,28]]},"references-count":22,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["genes13030442"],"URL":"https:\/\/doi.org\/10.3390\/genes13030442","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,28]]}}}