Mucopolysaccharidosis Type IIIE: A Real Human Disease or a Diagnostic Pitfall?

Overview

Journal Diagnostics (Basel)

Specialty Radiology

Date 2024 Aug 29

PMID 39202222

Authors

Karolina Wisniewska

Jakub Wolski

Magdalena Zabinska

Aneta Szulc

Lidia Gaffke

Karolina Pierzynowska

Grzegorz Wegrzyn

Affiliations

Soon will be listed here.

Abstract

Mucopolysaccharidoses (MPS) comprise a group of 12 metabolic disorders where defects in specific enzyme activities lead to the accumulation of glycosaminoglycans (GAGs) within lysosomes. This classification expands to 13 when considering MPS IIIE. This type of MPS, associated with pathogenic variants in the gene, has thus far been described only in the context of animal models. However, pathogenic variants in this gene also occur in humans, but are linked to a different disorder, Usher syndrome (USH) type IV, which is sparking increasing debate. This paper gathers, discusses, and summarizes arguments both for and against classifying dysfunctions of arylsulfatase G (due to pathogenic variants in the gene) in humans as another subtype of MPS, called MPS IIIE. Specific difficulties in diagnostics and the classification of some inherited metabolic diseases are also highlighted and discussed.

Citing Articles

Mucopolysaccharidoses types I and IIIA: Diagnosis and identification of novel polymorphisms associated with common mutations in Moroccan patients.

El Fissi H, Bouzid F, Sebbar M, Serghini M, Msanda F, Alif N Mol Genet Metab Rep. 2025; 42:101186.

PMID: 39897474 PMC: 11787024. DOI: 10.1016/j.ymgmr.2025.101186.

Mucopolysaccharidosis-Plus Syndrome: Is This a Type of Mucopolysaccharidosis or a Separate Kind of Metabolic Disease?.

Cyske Z, Gaffke L, Pierzynowska K, Wegrzyn G Int J Mol Sci. 2024; 25(17).

PMID: 39273517 PMC: 11395409. DOI: 10.3390/ijms25179570.

References

Holanda I, Rim P, Rare Genomes Project Consortium , Guaragna M, Gil-da-Silva-Lopes V, Steiner C . Syndromic Retinitis Pigmentosa: A 15-Patient Study. Genes (Basel). 2024; 15(4). PMC: 11050127. DOI: 10.3390/genes15040516. View

Ryazantsev S, Yu W, Zhao H, Neufeld E, Ohmi K . Lysosomal accumulation of SCMAS (subunit c of mitochondrial ATP synthase) in neurons of the mouse model of mucopolysaccharidosis III B. Mol Genet Metab. 2006; 90(4):393-401. PMC: 1892176. DOI: 10.1016/j.ymgme.2006.11.006. View

Tomatsu S, Pitz S, Hampel U . Ophthalmological Findings in Mucopolysaccharidoses. J Clin Med. 2019; 8(9). PMC: 6780167. DOI: 10.3390/jcm8091467. View

Cocostirc V, Pastiu A, Pusta D . An Overview of Canine Inherited Neurological Disorders with Known Causal Variants. Animals (Basel). 2023; 13(22). PMC: 10668755. DOI: 10.3390/ani13223568. View

Winner L, Rogers M, Snel M, Hemsley K . Biomarkers for predicting disease course in Sanfilippo syndrome: An urgent unmet need in childhood-onset dementia. J Neurochem. 2023; 166(3):481-496. DOI: 10.1111/jnc.15891. View

Mohammed E, Fayez A, Abdelfattah N, Fateen E . Novel gene-specific Bayesian Gaussian mixture model to predict the missense variants pathogenicity of Sanfilippo syndrome. Sci Rep. 2024; 14(1):12148. PMC: 11130188. DOI: 10.1038/s41598-024-62352-0. View

Bauwens M, Storch S, Weisschuh N, Ceuterick-de Groote C, De Rycke R, Guillemyn B . Functional characterization of novel MFSD8 pathogenic variants anticipates neurological involvement in juvenile isolated maculopathy. Clin Genet. 2019; 97(3):426-436. PMC: 7064892. DOI: 10.1111/cge.13673. View

Kowalewski B, Lubke T, Kollmann K, Braulke T, Reinheckel T, Dierks T . Molecular characterization of arylsulfatase G: expression, processing, glycosylation, transport, and activity. J Biol Chem. 2014; 289(40):27992-8005. PMC: 4183830. DOI: 10.1074/jbc.M114.584144. View

Del Longo A, Piozzi E, Schweizer F . Ocular features in mucopolysaccharidosis: diagnosis and treatment. Ital J Pediatr. 2018; 44(Suppl 2):125. PMC: 6238255. DOI: 10.1186/s13052-018-0559-9. View

10.

Celik B, Tomatsu S, Tomatsu S, Khan S . Epidemiology of Mucopolysaccharidoses Update. Diagnostics (Basel). 2021; 11(2). PMC: 7916572. DOI: 10.3390/diagnostics11020273. View

11.

Abitbol M, Thibaud J, Olby N, Hitte C, Puech J, Maurer M . A canine Arylsulfatase G (ARSG) mutation leading to a sulfatase deficiency is associated with neuronal ceroid lipofuscinosis. Proc Natl Acad Sci U S A. 2010; 107(33):14775-80. PMC: 2930459. DOI: 10.1073/pnas.0914206107. View

12.

. MPS screening methods, the Berry spot and acid turbidity tests, cause a high incidence of false-negative results in sanfilippo and morquio syndromes. J Clin Lab Anal. 2002; 16(5):253-8. PMC: 6808023. DOI: 10.1002/jcla.10051. View

13.

Kruszewski K, Lullmann-Rauch R, Dierks T, Bartsch U, Damme M . Degeneration of Photoreceptor Cells in Arylsulfatase G-Deficient Mice. Invest Ophthalmol Vis Sci. 2016; 57(3):1120-31. DOI: 10.1167/iovs.15-17645. View

14.

Wolfberg J, Chintalapati K, Tomatsu S, Nagao K . Hearing Loss in Mucopolysaccharidoses: Current Knowledge and Future Directions. Diagnostics (Basel). 2020; 10(8). PMC: 7460463. DOI: 10.3390/diagnostics10080554. View

15.

Kowalewski B, Lange H, Galle S, Dierks T, Lubke T, Damme M . Decoding the consecutive lysosomal degradation of 3-O-sulfate containing heparan sulfate by Arylsulfatase G (ARSG). Biochem J. 2021; 478(17):3221-3237. DOI: 10.1042/BCJ20210415. View

16.

Ku C, Hull S, Arno G, Vincent A, Carss K, Kayton R . Detailed Clinical Phenotype and Molecular Genetic Findings in CLN3-Associated Isolated Retinal Degeneration. JAMA Ophthalmol. 2017; 135(7):749-760. PMC: 5710208. DOI: 10.1001/jamaophthalmol.2017.1401. View

17.

Kingma S, Ceulemans B, Kenis S, Jonckheere A . Are GMI gangliosidosis and Morquio type B two different disorders or part of one phenotypic spectrum?. JIMD Rep. 2021; 59(1):90-103. PMC: 8100397. DOI: 10.1002/jmd2.12204. View

18.

Igelman A, Ku C, Palma M, Georgiou M, Schiff E, Lam B . Expanding the clinical phenotype in patients with disease causing variants associated with atypical Usher syndrome. Ophthalmic Genet. 2021; 42(6):664-673. PMC: 9233901. DOI: 10.1080/13816810.2021.1946704. View

19.

Kido J, Nakamura K, Era T . Role of induced pluripotent stem cells in lysosomal storage diseases. Mol Cell Neurosci. 2020; 108:103540. DOI: 10.1016/j.mcn.2020.103540. View

20.

Elleder M, Sokolova J, Hrebicek M . Follow-up study of subunit c of mitochondrial ATP synthase (SCMAS) in Batten disease and in unrelated lysosomal disorders. Acta Neuropathol. 1997; 93(4):379-90. DOI: 10.1007/s004010050629. View