fucosidosis
Fucosidosis is a rare inherited autosomal recessive lysosomal storage disorder, hypomyelinating disorder, and mucopolysaccharidosis-like disorder, characterized by multiorgan accumulation of fucose-containing products.
Epidemiology
It is considered very rare, with approximately only 100 cases described in the literature .
Clinical presentation
Typical clinical features, as described in decreasing order of frequency in one relatively large case series, include :
- progressive intellectual disability with eventual dementia
- progressive motor deterioration: initially hypotonia before spasticity manifests
- coarse facies
- dwarfism and other musculoskeletal anomalies
- recurrent respiratory infections
- angiokeratomas
- organomegaly: glossomegaly, hepatomegaly, splenomegaly, and cardiomegaly
- seizures
The temporal progression of these clinical features can vary, and as such, two clinical phenotypes have been described based on temporal progression of the disease :
- type I: rapidly progressive course, with death typically in infancy
- type II: milder course, with death typically in adulthood
However, many authors contend that fucosidosis should instead be thought of having a phenotypic spectrum, rather than two distinct types, given many patients lie in between types I and II .
Pathology
Fucosidosis is caused by a mutation in the FUCA1 gene on chromosome 1p34, which is inherited in an autosomal recessive fashion . This gene encodes for alpha-L-fucosidase, which normally catalyzes the breakdown of various fucose-containing oligosaccharides, glycoproteins, and glycolipids . In fucosidosis, there is an absence or near-absence of this enzyme and function, and thus these fucose-containing products accumulate within the body and deposit within various organs, such as the brain .
Radiographic features
Although fucosidosis is a multisystem disease, neuroimaging features are most commonly described. In addition to neuroimaging features, patients will also have non-specific features of organomegaly and dysostosis multiplex .
CT
CT features of fucosidosis are rarely described, but include hypodensity of the corona radiata, globi pallidi, and thalamus . Additionally, generalized cerebral and cerebellar atrophy has also been noted .
MRI
MRI is the modality of choice, where abnormalities of both white and grey matter can be detected in fucosidosis.
In the white matter, there is evidence of hypomyelination, with extensive, confluent, progressive, and symmetric signal anomaly in the periventricular and subcortical white matter . This white matter signal anomaly manifests as hyperintense on T2/FLAIR sequences, while T1 sequences are often unremarkable .
In the grey matter, fucosidosis is characterized by signal changes in the globi pallidi . This manifests as marked hypointensity on T2/FLAIR sequences, and hyperintensity on T1 sequences . This is a finding unique to fucosidosis among lysosomal storage diseases .
Furthermore, as seen on CT, generalized cerebral and cerebellar atrophy is also noted as the disease progresses . Given atrophy is a chronic process, it is more commonly noted in patients with the type II phenotype .
MR spectroscopy
Although infrequently reported, MR spectroscopy findings include a decreased NAA/choline ratio and a characteristic abnormal peak at 3.8 ppm . This peak is thought to represent resonance of fucose-containing macromolecules such as oligosaccharides and glycolipids .
Treatment and prognosis
Although bone marrow transplant has been reported as an effective treatment, this is very uncommonly performed, and only after careful patient selection . Furthermore, unlike other inborn errors of metabolism, unfortunately enzyme replacement therapy and substrate inhibition are not yet (as of March 2019) available . Thus, the cornerstone of management is generally supportive with physiotherapy and other allied health input .
History and etymology
The first case of fucosidosis was described by Italian pediatrician P Durand et al. in their 1966 seminal case series .
Siehe auch:
