Severe Hypomyelination as the Leading Neuroradiological Sign in a Patient with Fucosidosis

Abstract

Fucosidosis is a rare autosomal recessive lysosomal storage disease, resulting from a deficiency of alpha- L-fucosidase. We report on the clinical and MRI findings of a girl with this disorder. Developmental delay became obvious at an age between 6 and 12 months. Cranial MRI at 16 months revealed severe global hypomyelination of both supra- and infratentorial white matter but no involvement of basal ganglia or thalamus. No clinical signs typical for fucosidosis were present at this time, and psychomotor development still progressed slowly. Since the age of 2 years, progressive neurological deterioration occurred. The diagnosis was established by severely decreased activity of alpha- L-fucosidase in plasma and leukocytes and confirmed by the detection of compound heterozygosity for two missense mutations of the FUCA1 gene. A follow-up imaging at the age of 4 years showed progression of neuroradiological abnormalities, particularly progressive involvement of basal ganglia and thalami. The course of this patient and her MRI findings enlarge the clinical and neuroradiological spectrum of fucosidosis.

Magnetic resonance imaging pattern recognition in hypomyelinating disorders

“…However, T 2 hypointensity of the globus pallidus has been reported in fucosidosis only (Provenzale et al, 1995;Inui et al, 2000). The magnetic resonance images published by Prietsch et al (2008) show that the lateral geniculate bodies have a low T 2 signal as well. This can also be seen in two of our patients.…”

“…Over the last few decades, several new hypomyelinating disorders and their genetic defects have been identified. They include Salla disease (Sonninen et al, 1999), Cockayne syndrome (Nishio et al 1988), Tay syndrome (also called trichothiodystrophy with hypersensitivity of the skin to sunlight) (Østergaard and Christensen, 1996), oculodentodigital dysplasia (Gutmann et al, 1991;Loddenkemper et al, 2002), Waardenburg-Hirschsprung syndrome with peripheral neuropathy and central hypomyelination (Inoue et al, 1999(Inoue et al, , 2002, serine synthesis defects (Jaeken et al, 1996;de Koning et al, 2000), fucosidosis (Provenzale et al, 1995;Galluzzi et al, 2001, Prietsch et al, 2008, 18q À syndrome (Miller et al, 1990, Loevner et al, 1996, Gay et al, 1997, hypomyelination with atrophy of the basal ganglia and cerebellum (HABC) (Van der Knaap et al, 2002), hypomyelination with congenital cataract (HCC) (Zara et al, 2006, Rossi et al, 2008, Pelizaeus-Merzbacher-like disease (PMLD) (Uhlenberg et al, 2004;Bugiani et al, 2006) and hypomyelination with hypogonadotropic hypogonadism and hypodontia (4H syndrome) (Wolf et al, 2005;Timmons et al, 2006). It is important to also realize that neuronal disorders with early infantile onset, like infantile GM1 and GM2 gangliosidosis (Fukumizu et al, 1992;Koelfen et al, 1994;Mugikura et al, 1996, Shen et al, 1998, Lin et al, 2000 can present with hypomyelination on MRI scans (Schiffmann and van der Knaap, 2009).…”

Secondary biochemical and morphological consequences in lysosomal storage diseases

“…It was hypothesized that in β man nosidosis this phenomenon is secondary compared to decreased thyroid hormone level [64]. Severe hypomyeli nation has been described in a patient with fucosidosis [65]. In dogs with fucosidosis, the severe progressive brain lesions involved perivascular storage, gliosis, axonal dys morphia, and apoptosis [66].…”

Identification of Five Novel Mutations Causing Rare Lysosomal Storage Diseases

“…Type I has a severe infantile presentation (neurological functions impairment starting before 1 year of age) and severe skeletal malformations; type II has progressive features (dermal system impairing obviously). In our study, Patient 2 had no dermal system signs for fucosidosis, just mild skeletal symptoms and psychomotor retardation, and his presentations look like a German case [9], which was more inclined to belong to type I. Nonsense mutation c.717C>A in FUCA1 can lead to atypical fucosidosis Type I.…”