α-Fucosidase Deficiency: A Rare Differential Diagnosis of the Eye-of-the-Tiger Sign and Extrapyramidal Movement Disorders

Background: The eye-of-the-tiger sign in cMRI is a feature associated with syndromes of neurodegeneration with brain iron accumulation (NBIA). White matter changes are atypical for NBIA diseases. We present a case of a 6-year-old patient of consanguineous parents from Tajikistan, who showed developmental regression, seizures, extrapyramidal movement disorders, coarsening of facial features, angiokeratomas, and eye-of-the-tiger sign and white matter changes in cMRI.

Methods:

Cranial MRI scan

NBIA-panel

Exclusion of manganese and copper metabolic disorders

Enzymatic analysis of α-fucosidase-activity

Thin-layer chromatography of oligosaccharides

Results: cMRI: T2-weighted sequences increased signal intensity of the periventricular layer, radiating into U-fibers. There is substantial signal reduction in T2-weighted sequences in globus pallidus, less in substantia nigra and nucleus ruber with minimal T1 hyperintensity in globus pallidus. Mild eye-of-the-tiger sign. Metabolic analysis: distinctive peak for oligosaccharides in urine enzymatic analysis—activity reduction pf the α-fucosidase to 1.6%, from mean of healthy controls. With eye-of-the-tiger sign in cMRI we first considered an NBIA, which was excluded by genetic panel. With Angiokeratosis on extremities as clinical finding, we focused on thin-layer chromatography of oligosaccharides in urine, which showed a distinctive pattern of fucosidosis, followed by enzymatic analysis for α-fucosidase-deficiency. This was confirmed by reduced activity of the enzyme.

Conclusion: Fucosidosis should be considered when finding an eye-of-the-tiger-sign and white matter changes combined with extrapyramidal movement disorders and angiokeratosis.