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Multiple sulfatase deficiency

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Multiple sulfatase deficiency
Other namesJuvenile sulfatidosis, Austin type
Multiple sulfatase deficiency is autorecessive
SpecialtyEndocrinologyEdit this on Wikidata

Multiple sulfatase deficiency(MSD), also known asAustin disease,[1]ormucosulfatidosis,[1]is a very rareautosomal recessive[2]lysosomal storage disease[3]caused by a deficiency in multiplesulfataseenzymes, or informylglycine-generating enzyme,which activates sulfatases.[4]: 502 [5]It is similar tomucopolysaccharidosis.[6]

Signs and symptoms

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Symptoms of this disorder commonly appear between one and two years of age. Symptoms include mildly coarsened facial features, deafness,ichthyosis[7]and an enlarged liver and spleen (hepatosplen Omega ly).[8]Abnormalities of the skeleton, such as a curving of the spine and breast bone may occur. The skin of individuals afflicted with this disorder, is typically dry.[9]Children affected by this disorder develop more slowly than normal and may display delayed speech and walking skills.[9]

The disease is fatal, with symptoms that include neurological damage and severemental retardation.[10]These sulfatase enzymes are responsible for breaking down and recycling complex sulfate-containing sugars fromlipidsandmucopolysaccharideswithin thelysosome.The accumulation of lipids and mucopolysaccharides inside the lysosome results in symptoms associated with this disorder. As of 2018,75–100 cases of MSD had been reported worldwide.[9]

Causes

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Multiple sulfatase deficiency is caused by any mutation of theSUMF1gene which renders its protein product, theformylglycine-generating enzyme(FGE), defective.[11][12]These mutations result in inactive forms of FGE.[13]This enzyme is required forposttranslational modificationof a cysteine residue in the sulfatase enzyme active site into formylglycine,[14]which is required for its proper function.[15]

Genetics

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MSD has anautosomal recessiveinheritance pattern.[2] The inheritance probabilitiesper birthare as follows:

  • If both parents are carriers:
    • 25% (1 in 4) children will have the disorder
    • 50% (2 in 4) children will be carriers (but unaffected)
    • 25% (1 in 4) children will be free of MSD - unaffected child that is not a carrier
  • If one parent is affected and one is free of MSD:
    • 0% (0) children will have the disorder - only one parent is affected, other parent always gives normal gene
    • 100% (4 in 4) children will be carriers (but unaffected)
  • If one parent is a carrier and the other is free of MSD:
    • 50% (2 in 4) children will be carriers (but unaffected)
    • 50% (2 in 4) children will be free of MSD - unaffected child that is not a carrier

Diagnosis

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MSD may be diagnosed when deficiency of more than one sulfatase enzyme is identified inleukocytesorfibroblasts,[16]or by moleculargenetic testingwhich shows pathogenic variation in both alleles of theSUMF1gene.[9]

Treatment

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As there is no cure for MSD, treatment is restricted to management of symptoms.[16] There is much research on MSD that is currently underway. MSD Action Foundation have initiated more than 15 research projects on MSD in the last 6 years. Many of these have a translational focus. It is hoped that clinical trials for MSD will happen in the not too distant future- Alan Finglas. [Ref 17. Finglas 2020]

See also

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References

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  1. ^abRapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007).Dermatology: 2-Volume Set.St. Louis: Mosby.ISBN978-1-4160-2999-1.
  2. ^abJames, William D.; Elston, Dirk; Treat, James R.; Rosenbach, Misha A.; Neuhaus, Isaac (2020)."27. Genodermatoses and congenital anomalies".Andrews' Diseases of the Skin: Clinical Dermatology(13th ed.). Edinburgh: Elsevier. pp. 563–565.ISBN978-0-323-54753-6.
  3. ^Dierks, T; Schmidt, B; Borissenko, Lv; Peng, J; Preusser, A; Mariappan, M; Von, Figura K (May 2003)."Multiple sulfatase deficiency is caused by mutations in the gene encoding the human C( Alpha )-formylglycine generating enzyme".Cell.113(4): 435–44.doi:10.1016/S0092-8674(03)00347-7.PMID12757705.S2CID11571659.
  4. ^Freedberg, et al. (2003).Fitzpatrick's Dermatology in General Medicine.(6th ed.). McGraw-Hill.ISBN0-07-138076-0.
  5. ^Schmidt, B; Selmer, T; Ingendoh, A; Von, Figura K (July 1995)."A novel amino acid modification in sulfatases that is defective in multiple sulfatase deficiency".Cell.82(2): 271–8.doi:10.1016/0092-8674(95)90314-3.PMID7628016.S2CID5864312.
  6. ^Soong BW, Casamassima AC, Fink JK, Constantopoulos G, Horwitz AL (1988). "Multiple sulfatase deficiency".Neurology.38(8): 1273–5.doi:10.1212/wnl.38.8.1273.PMID2899861.S2CID35222500.
  7. ^The American Heritage Medical Dictionary: mucosulfatidosis
  8. ^Burk, R; Valle, D; Thomas, GH; Miller, C; Moser, A; Moser, H; Rosenbaum, KN (1984). "Early manifestations of multiple sulfatase deficiency†".The Journal of Pediatrics.104(4): 574–8.doi:10.1016/S0022-3476(84)80550-8.PMID6142938.
  9. ^abcdSchlotawa, L; Adang, L; De Castro, M; Ahrens-Nicklas, R (2019). "Multiple sulfatase deficiency". In Adam, MP; Ardinger, HH; Pagon, RA; Wallace, SE; Bean, LJH; Mirzaa, G; Amemiya, A (eds.).GeneReviews.PMID30896912.
  10. ^Farooqui AA, Horrocks LA (1984). "Biochemical aspects of globoid and metachromatic leukodystrophies".Neurochem Pathol.2(3): 189–218.doi:10.1007/BF02834352.PMID6152665.S2CID36099212.
  11. ^Cosma MP, Pepe S, Annunziata I (May 2003)."The multiple sulfatase deficiency gene encodes an essential and limiting factor for the activity of sulfatases".Cell.113(4): 445–56.doi:10.1016/S0092-8674(03)00348-9.PMID12757706.S2CID15095377.
  12. ^Annunziata I, Bouchè V, Lombardi A (September 2007)."Multiple sulfatase deficiency is due to hypomorphic mutations of the SUMF1 gene".Human Mutation.28(9): 298.doi:10.1002/humu.9504.PMID17657823.S2CID8500605.
  13. ^Dierks T, Schmidt B, Borissenko LV (May 2003)."Multiple sulfatase deficiency is caused by mutations in the gene encoding the human C( Alpha )-formylglycine generating enzyme".Cell.113(4): 435–44.doi:10.1016/S0092-8674(03)00347-7.PMID12757705.S2CID11571659.
  14. ^Preusser-Kunze A, Mariappan M, Schmidt B, Gande SL, Mutenda K, Wenzel D, von Figura K, Dierks T (April 2005)."Molecular Characterization of the Human C( Alpha )-formylglycine-generating Enzyme".Journal of Biological Chemistry.280(15): 14900–14910.doi:10.1074/jbc.M413383200.PMID15657036.
  15. ^Landgrebe J, Dierks T, Schmidt B (October 2003)."The human SUMF1 gene, required for posttranslational sulfatase modification, defines a new gene family which is conserved from pro- to eukaryotes".Gene.316:47–56.doi:10.1016/S0378-1119(03)00746-7.PMID14563551.
  16. ^abSchlotawa, L; Adang, LA; Radhakrishnan, K; Ahrens-Nicklas, RC (13 May 2020)."Multiple sulfatase deficiency: A disease comprising mucopolysaccharidosis, sphingolipidosis, and more caused by a defect in posttranslational modification".International Journal of Molecular Sciences.21(10): 3448.doi:10.3390/ijms21103448.PMC7279497.PMID32414121.

[17] View from inside: When multiple sulfatase deficiency changes everything about how you live and becomes your life Alan Finglas, https://doi.org/10.1002/jimd.12305

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