Phenotypic spectrum of fucosidosis in Tunisia

Abstract

Fucosidosis (OMIM 230000) is a rare autosomal recessive lysosomal disorder due to deficient α-L-fucosidase activity(EC 3.2.1.51), leading to the accumulation of fucose-containing glycolipids and glycoproteins in various tissues. This study contained the largest ever Tunisian survey of fucosidosis patients, diagnosed during the period 1987-2007. The clinical pictures and outcomes of these patients are compared with literature data. Ten patients (8 boys and 2 girls) from six unrelated families were diagnosed at a mean age of 29 ± 10.3 months. Six of the patients were diagnosed as having the more severe phenotype. The other four cases presented the low progressive phenotype. This distinction was determined by the presence or absence of angiokeratoma and age of death. For all of the patients in our survey, early motor development was more severely delayed than described in the literature. Six patients presented psychomotor decline during the second year of life. Clinical features consist of variable mental retardation (all patients), progressive spastic quadriplegia (6/10 cases), coarse facies (9/10 cases), growth retardation (7/9 cases), visceromegaly (3 cases), angiokeratoma corporis diffusum (4 cases), recurrent bronchopneumonias (all cases), seizures (4 cases) and variable degrees of dysostosis multiplex (all cases). Portal cavernoma, never described in the literature, was observed in one patient. The outcomes were severe in this survey, probably owing to restricted health care; death occurred in 6 of the 10 patients before age 10 years, following recurrent pulmonary infections and neurological deterioration. No intrafamilial variability was noted in the multiplex families. The clinical presentation and outcomes of some of these patients were consistent with the continuous clinical spectrum of severity in fucosidosis attested by most clinical studies.

Neuronopathic lysosomal storage diseases: Clinical and pathologic findings

“…b-Hexosaminidase A (Hex A) deficiencies result from the defects of its a-(HEXA) or b-(HEXB) subunits (EC 3.2.1.52). HEXA mutations result in the Tay-Sachs diseases (TSDs), whereas HEXB mutations cause the Sandhoff diseases, or Variant 0: so called owing to the defects in both HexA and HexB enzymes [Willems et al, 1991;Ben et al, 2008]. HexA is a trimer of ab 2 and HexB is a tetramer of b 4 .…”

“…Although the disorder is panethnic, the majority of reported patients have been from Calabria (Italy) and the United States [Lacey and Terplan, 1984;Verghese et al, 2000]. The prevalence is unknown, but seems to be a rare and underestimated disorder [Ben et al, 2008].…”

Diagnosis of Fucosidosis through Cutaneous Manifestations

“…Fucosidosis (MIM 230000) is a rare autosomal recessive lysosomial storage disease due to α-L-fucosidase deficiency resulting in multisystem accumulation of oligosaccharides and shingoglycolipids. The disease presents with progressive mental retardation, motor deterioration, coarse facies, growth retardation, recurrent respiratory infections, dysostosis, visceromegaly and seizure [2]- [4].…”

“…The presence of angiokeratomas is correlated to intermediate forms of fucosidosis, and they become more common with increasing age [3] [4].…”

Siblings with fucosidosis

“…Type I presents in infancy with a very rapid progression of illness and death in early childhood, whereas type II presents later with lesser severity although it is gradually progressive, and sometimes people survive into adulthood. [12] So far around 100 cases have been reported worldwide with only one case from India. Here, we present two siblings with fucosidosis with characteristic clinical, radiological and laboratory features with a brief review of the literature.…”