Fucosidosis
General description
Fucosidosis represents a rare autosomal recessive lysosomal storage disorder caused by biallelic pathogenic variants in the FUCA1 gene located on chromosome 1p36.11, leading to deficiency of the lysosomal hydrolase α-L-fucosidase. This enzyme normally catalyzes the cleavage of α1,2-, α1,3-, α1,4-, and α1,6-linked fucosyl residues within glycoconjugates, facilitating the breakdown of fucose-containing glycoproteins, glycolipids, and oligosaccharides.
Fucosidosis presents with a characteristic constellation of progressive neurological and systemic manifestations. The clinical picture is dominated by progressive mental deterioration and motor deterioration. Coarse facial features and growth retardation are observed. Recurrent respiratory infections represent another common feature, contributing to significant morbidity.
Systemic manifestations include dysostosis multiplex, characterized by skeletal abnormalities affecting the spine, pelvis, and long bones. Angiokeratoma corporis diffusum occurs, representing a distinctive dermatological feature. Visceromegaly may also present, reflecting the multi-organ nature of the storage disorder. Additional features include cardiomegaly, hepatomegaly, inguinal hernia, and hearing loss.
The neurological manifestations include seizures and progressive loss of previously acquired skills. Motor symptoms encompass ataxia, spasticity, and hypotonia, resulting from lysosomal burden in motor neurons and associated pathways.
MR spectroscopy
MRS typically shows a decrease in NAA, reflecting neuronal loss. In addition, it characteristically reveals an increased peak at 3.8–3.9 ppm on short TE, corresponding to the accumulation of macromolecules containing fucose, and an inverted peak at 1.2 ppm on long TE.
References
- Galluzzi, Paolo, et al. "MR brain imaging of fucosidosis type I." American journal of neuroradiology 22.4 (2001): 777-780.
- Steenweg, Marjan E., et al. "Magnetic resonance imaging pattern recognition in hypomyelinating disorders." Brain 133.10 (2010): 2971-2982.
White matter lesion
MRI reveals extensive and progressive white matter changes.
Globus pallidus and substantia nigra
The globus pallidus and substantia nigra demonstrate characteristic signal alterations with high signal intensity on T1-weighted images and low signal intensity on T2-weighted and FLAIR sequences. These changes are present bilaterally and symmetrically, creating a pathognomonic appearance that aids in diagnosis. Similar to other lysosomal storage diseases, bilateral thalami demonstrate T2-weighted and FLAIR hypointensity.
Medial and lateral medullary laminae of globus pallidus
Within the globus pallidus, curvilinear streaks of abnormal signal intensity are evident, representing the medial and lateral medullary laminae. These structures show hyperintensity on T2-weighted images, contrasting with the hypointense pallidal parenchyma.