Fucosidosis revisited: A review of 77 patients

Abstract

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. (J. 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 cross-reacting 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.

Spectrum of mutations in fucosidosis

“…5,6 All but two mutations were found in homozygous form, confirming the very high rate of consanguinity found in fucosidosis families. 4 The different mutations are discussed below. The patients' initials refer to the appendix table in the review study by Willems et al 4 …”

“…Additional features are angiokeratoma corporis diffusum, dysostosis multiplex, visceromegaly, ocular abnormalities, hearing loss, seizures, coarse features, recurrent infections, spasticity, contractures, growth retardation, muscle wasting and dystrophy. [2][3][4] All these clinical abnormalities are progressive, leading to cachexia and early death. Although clinical heterogeneity with a very rapidly progressive course and death in infancy (type I), and a slightly milder variant with death in adulthood (type II) has been described, further studies have shown that fucosidosis has a wide continuous clinical spectrum without any evidence for real clinical heterogeneity.…”

“…Although clinical heterogeneity with a very rapidly progressive course and death in infancy (type I), and a slightly milder variant with death in adulthood (type II) has been described, further studies have shown that fucosidosis has a wide continuous clinical spectrum without any evidence for real clinical heterogeneity. 4 In a clinical review study compiling information from the literature and from an international questionnaire survey in North America, Western Europe, Japan and Australia, 77 patients affected with fucosidosis from 54 sibships have been reviewed. 4 A few additional patients have been reported after 1990, but in total less than 100 fucosidosis patients have been identified, indicating that the incidence of fucosidosis must be very low.…”

“…4 In a clinical review study compiling information from the literature and from an international questionnaire survey in North America, Western Europe, Japan and Australia, 77 patients affected with fucosidosis from 54 sibships have been reviewed. 4 A few additional patients have been reported after 1990, but in total less than 100 fucosidosis patients have been identified, indicating that the incidence of fucosidosis must be very low. The ethnic origin of fucosidosis has a worldwide distribution and fucosidosis patients have been reported in more than 20 different countries from Europe, North and South America, Asia and Africa.…”

Four year follow-up of a case of fucosidosis treated with unrelated donor bone marrow transplantation

“…1,2 Over the last few years, several storage diseases have been treated with hematopoietic stem cell transplantation (HSCT). [3][4][5][6] The enzymatic activity of white blood cells has been proven to rise to normal levels after HSCT.…”