Fucosidosis

Fucosidosis, often written Fucosidosis or referred to as α -L- fucosidase deficiency is a very rare autosomal recessive lysosomal storage disease belonging to the group of oligosaccharidoses.

Etiology

In the patients affected by the Fucosidosis the enzyme α -L- fucosidase is reduced in its activity. Cause of the enzyme defect is nonsense or missense mutations in the gene coding for α -L- fucosidase gene ( FUCA1 ), which is located on chromosome 1 p34 gene locus. The enzyme catalyzes the cleavage of L- fucose, or glycolipids and oligosaccharides containing fucose. The substrate is an essential monosaccharide fucose; specifically a hexose. The genetic defect caused by the reduction in the enzyme activity leads to an accumulation of non- metabolized fucose, or fucose compounds, in the cells in all tissues of the body. This buildup can cause damage in the cell and the institutions concerned.

In humans is located on chromosome 2, a pseudogene of FUCA1 on chromosome 6 and the polymorphic FUCA2 gene. The gene product of FUCA2 controls the enzyme activity in the blood serum, and in fibroblasts. To date, over 20 different mutations of FUCA1 were found, which can trigger a Fucosidosis.

Prevalence

The α -L- fucosidase deficiency is a very rare disease whose prevalence approximately 1: is 1 million. Been less than 100 cases have been reported worldwide, of which about 20 come from southern Italy in the villages Grotteria and Mammola in the area of Reggio Calabria. Another patient accumulation is found in the southwestern United States (New Mexico and Colorado). In the previously known 45 affected families consists of 40% consanguinity. The high prevalence in these populations can be partly explained by the founder effect.

Symptoms and diagnosis

A distinction is made between two different forms of the disease course, with the transitions between the two forms are fluid. The clinically more severe type 1 begins 3 to 18 months of age. The type 2 starts between 12 and 24 months and is characterized by a less progressive disease course. The life expectancy in type 2 is higher than in patients with type 1 also is still a third type of the disease discussed, which was described in two Dutch patients. There is a less pronounced, more juvenile form of the disease, in which no Lesions occur.

Typical symptoms of Fucosidosis are deformations of the face ( facial dysmorphia ) and skeletal malformations, severe mental retardation, seizures, enlarged liver ( hepatomegaly ), spleen (splenomegaly ) and the heart ( cardiomegaly ). In addition, are still deafness and angiokeratomas observed.

Diagnosis can be fucosidosis determine by chromatographic analysis of the urine of patients. Determining the activity of α -L- fucosidase in the leukocytes in the laboratory can secure the diagnosis. A genetic test is not necessary in most cases.

Therapy

The so far only, non- symptomatic, treatment with curative intent is the bone marrow transplant. Since only ten patients have been treated worldwide to date, this therapeutic approach can not yet be conclusively assessed. The method was first successfully tested in dogs.

Forecast

The first patient described by Paolo Durand and colleagues died in 1969, all in front of their fifth year of life. In a later study with a larger number of patients, however, only 9% of patients died before age five and 64% could reach the second decade of life.

First description

The Fucosidosis was first described in 1966 by Paolo Durand and colleagues in two Italian children and recognized as lysosomal storage disease. H. Loeb and colleagues were able to establish the lack of an active α -L- fucosidase as a cause of the disease three years later.

Veterinary Medicine

In veterinary medicine, the Canine Fucosidosis is a common, especially when English Springer Spaniel hereditary disease.