Fucosidosis revisited: A review of 77 patients

Fucosidosis is a rare, autosomal recessive, lysosomal storage disorder caused by a severe deficiency of alpha‐L‐fucosidase in all tissues. We have conducted a review of fucosidosis, compiling data from published reports and an international questionnaire survey. Seventy‐seven patients affected with fucosidosis of which 19 had not been reported before have been identified. A major aim of the present study was to define the natural history of fucosidosis. The clinical picture of fucosidosis consists of progressive mental (95%) and motor (87%) deterioration, coarse facies (79%), growth retardation (78%), recurrent infections (78%), dysostosis multiplex (58%), angiokeratoma corporis diffusum (52%), visceromegaly (44%), and seizures (38%). Whereas the original fucosidosis patients described by Durand et al. (Pediatr 75:665–674, 1969) were decerebrate and died before age 5 years, most fucosidosis patients have a slower course of degeneration. Mortality before age 5 years was observed in only 7 patients (9%), whereas 36 patients (64%) reached the second decade. We did not find evidence for the existence of clinical heterogeneity with a rapidly progressive type I and a slowly progressive type II fucosidosis as suggested in the literature. Instead, there seems to exist a wide continuous clinical spectrum. At the biochemical level no heterogeneity in residual fucosidase enzyme activity or crossreacting immunoreactive fucosidase protein was observed. At the DNA level at least 4 different mutations must be responsible for fucosidosis. These genotypic differences however do not explain the observed phenotypic differences.