Multiple sulfatase deficiency
Multiple sulfatase deficiency | |
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Other names | Juvenile sulfatidosis, Austin type |
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Multiple sulfatase deficiency is autorecessive | |
Specialty | Endocrinology ![]() |
Multiple sulfatase deficiency (MSD), also known as Austin disease,[1] 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]: 502 [5] It is similar to mucopolysaccharidosis.[6]
Signs and symptoms
[edit]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.[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 severe mental retardation.[10] 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. As of 2018[update], 75–100 cases of MSD had been reported worldwide.[9]
Causes
[edit]Multiple sulfatase deficiency is caused by any mutation of the SUMF1 gene which renders its protein product, the formylglycine-generating enzyme (FGE), defective.[11][12] These mutations result in inactive forms of FGE.[13] This enzyme is required for posttranslational modification of a cysteine residue in the sulfatase enzyme active site into formylglycine,[14] which is required for its proper function.[15]
Genetics
[edit]MSD has an autosomal recessive inheritance pattern.[2] The inheritance probabilities per birth are 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
[edit]MSD may be diagnosed when deficiency of more than one sulfatase enzyme is identified in leukocytes or fibroblasts,[16] or by molecular genetic testing which shows pathogenic variation in both alleles of the SUMF1 gene.[9]
Treatment
[edit]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
[edit]References
[edit]- ^ a b Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.
- ^ a b James, 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. ISBN 978-0-323-54753-6.
- ^ 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. PMID 12757705. S2CID 11571659.
- ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0.
- ^ 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. PMID 7628016. S2CID 5864312.
- ^ 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. PMID 2899861. S2CID 35222500.
- ^ The American Heritage Medical Dictionary: mucosulfatidosis
- ^ 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. PMID 6142938.
- ^ a b c d Schlotawa, 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. PMID 30896912.
- ^ Farooqui AA, Horrocks LA (1984). "Biochemical aspects of globoid and metachromatic leukodystrophies". Neurochem Pathol. 2 (3): 189–218. doi:10.1007/BF02834352. PMID 6152665. S2CID 36099212.
- ^ 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. PMID 12757706. S2CID 15095377.
- ^ 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. PMID 17657823. S2CID 8500605.
- ^ 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. PMID 12757705. S2CID 11571659.
- ^ 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. PMID 15657036.
- ^ 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. PMID 14563551.
- ^ a b Schlotawa, 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. PMC 7279497. PMID 32414121.
[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