Fucosidosis

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Classification according to ICD-10
E77.1 Defects in glycoprotein breakdown (including fucosidosis)
ICD-10 online (WHO version 2019)

Fucosidose , often Fukosidose written or α- L fucosidase deficiency called, is a very rare autosomal - recessive inherited lysosomal storage disease from the group of oligosaccharidoses .

etiology

In patients affected by fucosidosis, the activity of the enzyme α- L - fucosidase is reduced. Cause of this defect are nonsense - or missense - mutations in the α- for L -fucosidase -encoding gene ( FUCA1 ), located on one chromosomal locus p34 is located. The enzyme catalyzes the cleavage of L - fucose and of glycolipids and oligosaccharides containing fucose. The substrate fucose is an essential monosaccharide ; more precisely a hexosis . The reduced enzyme activity is not enriched metabolized fucose or fucosehaltige compounds in the cells of all tissues of the body. These accumulations lead to damage to the cell and the affected organs.

In humans there is a pseudogene of FUCA1 on chromosome 2 and the polymorphic FUCA2 gene on chromosome 6 . The gene product of FUCA2 controls the enzyme activity in blood serum and in fibroblasts . So far, more than 20 different mutations of FUCA1 have been found that can cause fucosidosis.

Prevalence

The α- L -fucosidase deficiency is a very rare disease, the prevalence of which is around 1: 1 million. Fewer than 100 patients have been described worldwide so far, of which around 20 come from southern Italy in the localities of Grotteria and Mammola in the Reggio Calabria area . Another cluster of patients can be found in the southwestern United States in New Mexico and Colorado . 40% of the 45 affected families known to date are consanguineous . The high prevalence in these populations can be partly explained by the founder effect .

Symptoms and diagnostics

A distinction is made between two forms of the disease, but their transitions are fluid. The clinically more severe type 1 begins between 3 and 18 months of age. Type 2 begins between the 12th and 24th month and is characterized by a less progressive course of the disease . The life expectancy in type 2 is higher than in patients with type 1. In addition, a third type of the disease is discussed, which has been described in two Dutch patients. It is a less severe, more juvenile form of the disease in which angiokeratomas do not occur.

Typical symptoms of fucosidosis are deformities of the face ( facial dysmorphism ) and malformations of the skeleton , severe mental retardation , seizures, enlargement of the liver ( hepatomegaly ), spleen ( splenomegaly ) and of the heart ( cardiomegaly ). Besides are deafness and angiokeratoma observed.

Fucosidosis can be diagnosed by chromatographic analysis of the patient's urine . The determination of the activity of the α- L -fucosidase in the leukocytes can confirm the findings in the laboratory. A genetic test is not necessary in most cases.

therapy

The only non-symptomatic treatment with a curative approach to date is bone marrow transplantation . Since only ten patients have been treated in this way worldwide, this therapeutic approach cannot yet be conclusively assessed. The method was first successfully tested on dogs.

forecast

The first patients described by Paolo Durand and colleagues in 1969 all died before they reached the age of five. In a later study with a larger number of patients, however, only 9% of the patients died before the age of five and 64% reached the second decade of life.

Initial description

Fucosidosis was first described in 1966 by Paolo Durand and colleagues in two Italian children and recognized as a lysosomal storage disease. Three years later, H. Loeb and colleagues established the lack of active α- L -fucosidase as the cause of the disease.

Veterinary medicine

In veterinary medicine , canine fucosidosis is a hereditary disease that is particularly common in English Springer Spaniels .

literature

  • G. Tiberio et al: Mutations in fucosidosis gene: a review. In: Acta Genet Med Gemellol (Roma) 44, 1995, pp. 223-232. PMID 8739734 (Review)
  • H. Cragg et al .: Fucosidosis: genetic and biochemical analysis of eight cases. In: J Med Genet 34, 1997, pp. 105-110; PMID 9039984 ; PMC 1050861 (free full text).
  • P. Durand et al: A new glycolipid storage disease. In: Pediat Res 1, 1967, p. 416.

Web links

Individual evidence

  1. ↑ P. Durand et al .: Fucosidosis. (Letter) In: The Lancet , Volume 291, 1968, p. 1198.
  2. ↑ a b P. J. Willems et al.: Spectrum of mutations in fucosidosis. In: Eur. J. Hum. Genet. , Volume 7, 1999, pp. 60-67. PMID 10094192 .
  3. ↑ S. Sangiorgi et al .: Genetic and demographic characterization of a population with high incidence of fucosidosis. In: Hum. Hered. , Volume 32, 1982, pp. 100-105. PMID 7095811 .
  4. ↑ BG Kousseff et al .: Fucosidosis type 2. In: Pediatrics , Volume 57, 1976, pp. 205-213. PMID 814528 .
  5. ↑ HC Schoonderwaldt et al .: Two patients with an unusual form of type II fucosidosis. In: Clin Genet. , Volume 18, 1980, pp. 348-354. PMID 7460371 .
  6. ↑ M. Zenker and others: Fucosidosis in two German patients - clinic and molecular genetics. In: Kinderheilkunde 146, 1998, pp. 323–327. doi : 10.1007 / s001120050276
  7. ↑ fucosidosis. In: Orphanet (Rare Disease Database).
  8. ↑ RM Taylor et al: Enzyme replacement in nervous tissue after allogeneic bone-marrow transplantation for fucosidosis in dogs. In: The Lancet, 328, 1986, pp. 772-774. PMID 2876234
  9. ↑ P. Durand et al .: Fucosidosis. In: J Pediat 75, 1969, pp. 665-674. PMID 4241464
  10. ↑ PJ Willems et al: Fucosidosis revisited: a review of 77 patients. In: Am J Med Genet 38, 1991, pp. 111-131. PMID 2012122 (Review)
  11. ^ P. Durand et al.: New mucopolysaccharide lipid storage disease. In: The Lancet 2, 1966, pp. 1313-1314. doi : 10.1016 / S0140-6736 (66) 91718-1
  12. ↑ H. Loeb et al: Biochemical and ultrastructural studies in a case of mucopolysaccharidosis F (fucosidosis). In: Helv Paediat Acta 24, 1969, pp. 519-537. PMID 4247654
  13. ^ BJ Skelly et al .: Genomic screening for fucosidosis in English Springer Spaniels. In: Am J Vet Res 60, 1999, pp. 726-729. PMID 10376901
  14. ↑ NG Holmes: A PCR-based diagnostic test for fucosidosis in English springer spaniels. In: Vet J 155, 1998, pp. 113-114. PMID 9564263
  15. ^ MO Smith et al: Fucosidosis in a family of American-bred English Springer Spaniels. In: J Am Vet Med Assoc 209, 1996, pp. 2088-2090. PMID 8960193
  16. ^ BJ Skelly et al.: The molecular defect underlying canine fucosidosis. In: J Med Genet 33, 1996, pp. 284-288; PMID 8730282 ; PMC 1050576 (free full text).
  17. ↑ Canine Fucosidosis accessed October 22, 2009