PEDBASE.org - The Pediatric Database -
Detailed information of FUCOSIDOSIS
FUCOSIDOSIS
DEFINITION:
A lysosomal storage disorder characterized by the accumulation of
lipids (glycosphingolipids) in the CNS and peripheral tissues
resulting in 2 clinical variants.
EPIDEMIOLOGY:
- incidence: rare (about 60 cases reported)
- age of onset:
- infancy (Type I) -> 1-2 years of age (Type II)
- risk factors:
- familial - autosomal recessive
- chrom.#: 1p34
- gene: alpha-fucosidase
- M = F
- panethnic but increased frequency in Italians and
Spanish-Americans
PATHOGENESIS:
- alpha-fucosidase is a homotetramer which catalyzes the
removal of fucose residues from glycosphingolipids
2. Genetic Defect
- genetic defect -> deficiency of alpha-fucosidase activity ->
accumulation of fucose-containing glycosphingolipids and glyco-proteins
in the CNS and peripheral tissues
- lungs, heart, liver, pancreas, kidneys, cornea, skin,
mucous-secreting glands, lymphocytes, peripheral nerves,
spleen
- major glycolipid accumulating is the H-antigen glycolipid
- two clinical variants:
CLINICAL FEATURES:
- 60% of cases
- early and rapid course with death around 5 years of age
- psychomotor retardation
- begin to fall off milestones around the end of 1st year
- weakness and hypotonia initially with eventual spastic
quadriplegia
- seizures
- progressive mental retardation
2. Gastrointestinal Manifestations
- hepatomegaly/hepatosplenomegaly
- macroglossia
- progressive impairment of gallbladder function
3. Musculoskeletal Manifestations
- brachycephalic skull
- frontal bossing
- coarse facial features
- growth retardation
- lumbar kyphosis
- joint contractures
4. Other Manifestations
- chronic recurrent lung infections
2. Cardiovascular
3. Ophthalmologic
- tortuous conjunctival vessels
- slight corneal clouding
- pigmentary retinopathy
4. Integument
2. Type II (Juvenile Form)
- 40% of cases
- later onset and slower course with survival into adulthood
- psychomotor retardation
- later onset with slower progression
- weakness and hypotonia initially with eventual
spasticity and contractures
2. Musculoskeletal Manifestations
- coarse facial features
- growth retardation -> dwarfism
3. Integument Manifestations
- indistinguishable from those seen in Fabry Disease with
similar distribution
- onset about 3 years of age
- small dark purple-blue telangiectasia
- most dense between the umbilicus and knees with
propensity for umbilicus and buttocks
- occasionally occur in mouth
INVESTIGATIONS:
- deficiency of alpha-fucosidase activity in leukocytes or
cultured skin fibroblasts (also samples from liver, lung,
kidney, & brain)
- prenatal
- deficiency of alpha-fucosidase activity in cultured
chorionic villi or amniocytes
2. Imaging Studies
- mild dysostosis multiplex
- lumbar kyphosis
- vertebrae - ovoid configuration with beaking of L2 and L3
- acetabula deformed and sclerotic
- widened shaft of long bones
2. CT/MRI
- progressive leukodystrophy with demyelination and gliosis
3. Chest X-Ray
3. Urine
- elevated fucose-rich oligosaccharides, sphingolipids,
glycopeptides (about 22 glycopeptides) detected by thin-layer
chrom-atography
- no mucopolysaccharides
4. Pathology
- biopsy of the liver (hepatocytes, Kupffer cells), skin,
conjunctiva shows vacuolization within the cells with some of
the vacuoles empty and others rich in glycosphingolipids and
glycoproteins
- these cytoplasmic vacuoles are surrounded by a single
mem-brane containing granular inclusions and lamellar bodies
5. Sweat Chloride
- positive in the Infantile Form
MANAGEMENT:
- no treatment for underlying disorder
- multidisciplinary approach
- Paediatrics, Neurology, Ophthalmology, Orthopedics
- genetic counselling
|
Pediatric Database - FUCOSIDOSIS
Pediatric Organization - Pedbase [at] Gmail.com