Multiple sulfatase deficiency explained

Synonyms:Juvenile sulfatidosis, Austin type
Multiple sulfatase deficiency

Multiple sulfatase deficiency (MSD), also known as Austin disease, or mucosulfatidosis,[1] is a very rare autosomal recessive[2] lysosomal storage disease[3] caused by a deficiency in multiple sulfatase enzymes, or in formylglycine-generating enzyme, which activates sulfatases.[4] [5] It is similar to mucopolysaccharidosis.[6]

Signs and symptoms

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 (hepatosplenomegaly).[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. Children affected by this disorder develop more slowly than normal and may display delayed speech and walking skills.

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

Causes

Multiple sulfatase deficiency is caused by any mutation of the SUMF1 gene which renders its protein product, the formylglycine-generating enzyme (FGE), defective.[10] [11] These mutations result in inactive forms of FGE.[12] This enzyme is required for posttranslational modification of a cysteine residue in the sulfatase enzyme active site into formylglycine,[13] which is required for its proper function.[14]

Genetics

MSD has an autosomal recessive inheritance pattern.[2] The inheritance probabilities per birth are as follows:

Diagnosis

MSD may be diagnosed when deficiency of more than one sulfatase enzyme is identified in leukocytes or fibroblasts,[15] or by molecular genetic testing which shows pathogenic variation in both alleles of the SUMF1 gene.[16]

Treatment

As there is no cure for MSD, treatment is restricted to management of symptoms.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

References

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

Notes and References

  1. Book: Rapini, Ronald P. . Bolognia, Jean L. . Jorizzo, Joseph L. . Dermatology: 2-Volume Set . Mosby . St. Louis . 2007 . 978-1-4160-2999-1 .
  2. Book: James . William D. . Elston . Dirk . Treat . James R. . Rosenbach . Misha A. . Neuhaus . Isaac . Andrews' Diseases of the Skin: Clinical Dermatology . 2020 . Elsevier . Edinburgh . 978-0-323-54753-6 . 563–565 . 13th . https://books.google.com/books?id=UEaEDwAAQBAJ&pg=PA563 . en . 27. Genodermatoses and congenital anomalies .
  3. 12757705 . May 2003 . Dierks, T . Schmidt, B . Borissenko, Lv . Peng, J . Preusser, A . Mariappan, M . Von, Figura K . Multiple sulfatase deficiency is caused by mutations in the gene encoding the human C(alpha)-formylglycine generating enzyme . 113 . 4 . 435–44 . Cell . 10.1016/S0092-8674(03)00347-7. 11571659 . free .
  4. Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. .
  5. 7628016 . July 1995 . Schmidt, B . Selmer, T . Ingendoh, A . Von, Figura K . A novel amino acid modification in sulfatases that is defective in multiple sulfatase deficiency . 82 . 2 . 271–8 . Cell . 10.1016/0092-8674(95)90314-3. 5864312 . free .
  6. Soong BW, Casamassima AC, Fink JK, Constantopoulos G, Horwitz AL . Multiple sulfatase deficiency . Neurology . 38 . 8 . 1273–5 . 1988 . 2899861 . 10.1212/wnl.38.8.1273. 35222500 .
  7. http://medical-dictionary.thefreedictionary.com/mucosulfatidosis The American Heritage Medical Dictionary: mucosulfatidosis
  8. 6142938 . 10.1016/S0022-3476(84)80550-8 . Early manifestations of multiple sulfatase deficiency† . 1984 . Burk, R . The Journal of Pediatrics . 104 . 574–8 . Valle . D . Thomas . GH . Miller . C . Moser . A . Moser . H . Rosenbaum . KN . 4.
  9. Farooqui AA, Horrocks LA . Biochemical aspects of globoid and metachromatic leukodystrophies . Neurochem Pathol . 2 . 3 . 189–218 . 1984 . 6152665 . 10.1007/BF02834352. 36099212 .
  10. Cosma MP, Pepe S, Annunziata I . The multiple sulfatase deficiency gene encodes an essential and limiting factor for the activity of sulfatases . Cell . 113 . 4 . 445–56 . May 2003 . 12757706 . 10.1016/S0092-8674(03)00348-9. 15095377 . free .
  11. Annunziata I, Bouchè V, Lombardi A . Multiple sulfatase deficiency is due to hypomorphic mutations of the SUMF1 gene . Human Mutation. 28 . 9. 298. September 2007. 17657823 . 10.1002/humu.9504. 8500605 . free.
  12. Dierks T, Schmidt B, Borissenko LV . Multiple sulfatase deficiency is caused by mutations in the gene encoding the human C(alpha)-formylglycine generating enzyme . Cell . 113 . 4 . 435–44 . May 2003 . 12757705 . 10.1016/S0092-8674(03)00347-7. 11571659 . free .
  13. Preusser-Kunze A, Mariappan M, Schmidt B, Gande SL, Mutenda K, Wenzel D, von Figura K, Dierks T . Molecular Characterization of the Human C(alpha)-formylglycine-generating Enzyme . Journal of Biological Chemistry. 280. 15 . 14900–14910. April 2005. 15657036 . 10.1074/jbc.M413383200. free.
  14. Landgrebe J, Dierks T, Schmidt B . 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. October 2003. 14563551 . 10.1016/S0378-1119(03)00746-7.
  15. Schlotawa . L . Adang . LA . Radhakrishnan . K . Ahrens-Nicklas . RC . Multiple sulfatase deficiency: A disease comprising mucopolysaccharidosis, sphingolipidosis, and more caused by a defect in posttranslational modification . International Journal of Molecular Sciences . 13 May 2020 . 21 . 10 . 3448 . 10.3390/ijms21103448 . free . 32414121 . 7279497.
  16. Book: Schlotawa . L . Adang . L . De Castro . M . Ahrens-Nicklas . R . Adam . MP . Ardinger . HH . Pagon . RA . Wallace . SE . Bean . LJH . Mirzaa . G . Amemiya . A . Multiple sulfatase deficiency . GeneReviews . 2019 . 30896912.

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