{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:59:32Z","timestamp":1760147972965,"version":"build-2065373602"},"reference-count":17,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T00:00:00Z","timestamp":1679356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dr. Jon Larsen\u2019s Foundation (Norway)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Multiple sulfatase deficiency (MSD) is an extremely rare autosomal recessively inherited disease with a prevalence of 1:500.000 caused by mutations on the sulfatase-modifying-Factor 1 gene (SUMF1). MSD is most specifically characterised by a combination of developmentally retarded psychomotoric functions, neurodegeneration that entails the loss of many already acquired abilities, and by ichthyosis. Other symptoms include those associated with mucopolysaccharidosis, i.e., facial dysmorphy, dwarfism, and hepatosplenomegaly. In 50\u201375% of all MSD-affected patients, functional or structural ocular damage is likely. MSD seldom affects the anterior segment of the eye. The main pathology these patients present is a highly conspicuous tapetoretinal degeneration, similar to severe Retinitis pigmentosa, that leads to blindness at an early age. An initially five-year-old boy with MSD, genetically verified at his first examination in our opthalmology department (SUMF1 mutations c.776A&gt;T, p.Asn259Ile; c.797A&gt;T, p.Pro266Leu; c.836A&gt;T, p.Ala279Val), and a 4, 5 year regular follow-up are described. The patient had some visual potential (\u201ctunnel view\u201d), which deteriorated dramatically after his fifth birthday. We observed no evidence of worsening retinal involvement in this patient in spite of his progressively worsening clinical symptoms, extending to total blindness\/no light perception. OCT revealed that the outer retinal layers containing photoreceptors were diseased; the ellipsoid zone was only partially discernible and the outer nuclear layer appeared to be thinned out. The inner nuclear layer, ganglion cell layer, and retinal nerve fibre layer were indistinguishable. These anomalies are indicative of a severe pathology within the retina\u2019s inner layers. Characteristic anomalies in the fundus should stimulate clinicians to suspect a case of MSD in their differential diagnosis, and thus to order thorough genetic and paediatric diagnostics.<\/jats:p>","DOI":"10.3390\/children10030595","type":"journal-article","created":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T03:15:03Z","timestamp":1679368503000},"page":"595","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Multiple Sulfatase Deficiency from an Ophthalmologist\u2019s Perspective\u2014Case Report and Literature Review"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6504-9532","authenticated-orcid":false,"given":"Michael P.","family":"Schittkowski","sequence":"first","affiliation":[{"name":"Section for Strabismus and Neuroophthalmology, Department of Ophthalmology, University Medical Centre Goettingen; Robert-Koch-Str. 40, 37085 Goettingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Naxer","sequence":"additional","affiliation":[{"name":"Section for Strabismus and Neuroophthalmology, Department of Ophthalmology, University Medical Centre Goettingen; Robert-Koch-Str. 40, 37085 Goettingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed","family":"Elabbasy","sequence":"additional","affiliation":[{"name":"Section for Strabismus and Neuroophthalmology, Department of Ophthalmology, University Medical Centre Goettingen; Robert-Koch-Str. 40, 37085 Goettingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonie","family":"Herholz","sequence":"additional","affiliation":[{"name":"Division for Neuropaediatrics, Department of Paediatrics and Adolescent Medicine, University Medical Centre Goettingen, 37075 Goettingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vivian","family":"Breitling","sequence":"additional","affiliation":[{"name":"Division for Neuropaediatrics, Department of Paediatrics and Adolescent Medicine, University Medical Centre Goettingen, 37075 Goettingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"Finglas","sequence":"additional","affiliation":[{"name":"MSD Action Foundation, D15 Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4108-7109","authenticated-orcid":false,"given":"Jutta","family":"G\u00e4rtner","sequence":"additional","affiliation":[{"name":"Division for Neuropaediatrics, Department of Paediatrics and Adolescent Medicine, University Medical Centre Goettingen, 37075 Goettingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7415-4905","authenticated-orcid":false,"given":"Lars","family":"Schlotawa","sequence":"additional","affiliation":[{"name":"Division for Neuropaediatrics, Department of Paediatrics and Adolescent Medicine, University Medical Centre Goettingen, 37075 Goettingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1002\/jimd.12282","article-title":"A systematic review and meta-analysis of published cases reveals the natural disease history in multiple sulfatase deficiency","volume":"43","author":"Schlotawa","year":"2020","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1002\/jimd.12298","article-title":"Natural history of multiple sulfatase deficiency: Retrospective phenotyping and functional variant analysis to characterize an ultra-rare disease","volume":"43","author":"Adang","year":"2020","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"133","DOI":"10.3928\/0191-3913-19840701-04","article-title":"Ocular Features of Multiple Sulfatase Deficiency and a New Variant of Metachromatic Leukodystrophy","volume":"21","author":"Bateman","year":"1984","journal-title":"J. Pediatr. Ophthalmol. Strabismus"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1212\/WNL.38.8.1273","article-title":"Multiple sulfatase deficiency","volume":"38","author":"Soong","year":"1988","journal-title":"Neurology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1097\/00005072-199007000-00005","article-title":"Multiple Sulfatase Deficiency: Clinical, Neuropathological, Ultrastructural and Biochemical Studies","volume":"49","author":"Guerra","year":"1990","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1177\/088307389100600304","article-title":"Multiple Sulfatase Deficiency with Early Severe Retinal Degeneration","volume":"6","author":"Harbord","year":"1991","journal-title":"J. Child Neurol."},{"key":"ref_7","first-page":"482","article-title":"Characterization of the arylsulfatase I (ARSI) gene preferentially expressed in the human retinal pigment epithelium cell line ARPE-19","volume":"15","author":"Oshikawa","year":"2009","journal-title":"Mol. Vis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/BF02263612","article-title":"Multiple sulphatase deficiency with early onset","volume":"4","author":"Vamos","year":"1981","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1159\/000305966","article-title":"Metachromatic Leucodystrophy","volume":"160","author":"Cogan","year":"1970","journal-title":"Ophthalmologica"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1017\/cjn.2014.12","article-title":"Case of Multiple Sulfatase Deficiency and Ocular Albinism: A Diagnostic Odyssey","volume":"41","author":"Prasad","year":"2014","journal-title":"Can. J. Neurol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1001\/archneur.1973.00490220066010","article-title":"Studies in Metachromatic Leukodystrophy. XII. Multiple sulfatase deficiency","volume":"28","author":"Austin","year":"1973","journal-title":"Arch. Neurol."},{"key":"ref_12","first-page":"436","article-title":"Combination of metachromatic leucodystrophy and mucopolysaccharidosis: A disease entity (mucosulfatidosis)","volume":"25","author":"Rampini","year":"1970","journal-title":"Helvetica Paediatr. Acta"},{"key":"ref_13","first-page":"775","article-title":"Mucosulfatidosis. Study of 3 familial cases","volume":"31","author":"Couchot","year":"1974","journal-title":"Arch. Fr. Pediatr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/S0022-3476(84)80550-8","article-title":"Early manifestations of multiple sulfatase deficiency","volume":"104","author":"Burk","year":"1984","journal-title":"J. Pediatr."},{"key":"ref_15","unstructured":"K\u00fcchle, M.N., and Naumann, G.O.H. (1997). Naumann GOH, Hrsg. Pathologie des Auges, Springer."},{"key":"ref_16","first-page":"1004","article-title":"A homozygous founder missense variant in arylsulfatase G abolishes its enzymatic activity causing atypical Usher syndrome in humans","volume":"20","author":"Khateb","year":"2018","journal-title":"Anesthesia Analg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1136\/jmedgenet-2021-108061","article-title":"Novel subtype of mucopolysaccharidosis caused by arylsulfatase K (ARSK) deficiency","volume":"59","author":"Verheyen","year":"2022","journal-title":"J. Med. Genet."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/10\/3\/595\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:59:16Z","timestamp":1760122756000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/10\/3\/595"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,21]]},"references-count":17,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["children10030595"],"URL":"https:\/\/doi.org\/10.3390\/children10030595","relation":{},"ISSN":["2227-9067"],"issn-type":[{"type":"electronic","value":"2227-9067"}],"subject":[],"published":{"date-parts":[[2023,3,21]]}}}