MR Imaging Findings in 2 Cases of Late Infantile GM1 Gangliosidosis

Abstract

SUMMARY:Late infantile GM1 gangliosidosis is a rare lysosomal disorder characterized by mental deterioration and progressive spastic, cerebellar, and extrapyramidal signs, without facial dysmorphisms and organomegaly. Neuroimaging findings have been reported in only a few cases. Here we report on predominant globus pallidus MR signal-intensity abnormalities in 2 patients with the late infantile form of GM1 gangliosidosis. GM1 gangliosidosis is a rare metabolic disorder due to deficiency of the lysosomal enzyme ␤-galactosidase, resulting in accumulation of GM1 gangliosides and other glycoconjugates in the brain and visceral organs. There are 3 clinical forms correlating with the degree of residual activity of the mutant enzyme. The infantile form (type 1) is a severe degenerative encephalopathy presenting between birth and 6 months with coarse facial features, skeletal dysostosis, and hepatosplenomegaly, leading to death within the first 2 years of life. Patients with the late infantile or juvenile form (type 2) present after 1 year of age with motor delay in the absence of dysmorphisms and organomegaly; later, mental deterioration and spastic, cerebellar, and extrapyramidal signs dominate the neurologic picture, probably as a consequence of predominant basal ganglia storage of gangliosides.1 The adult form (type 3) has a slowly progressive course and predominant extrapyramidal features without visceral or skeletal changes. 2Reports on the neuroimaging features of the very rare late infantile GM1 gangliosidosis are scant and have mainly included brain atrophy and white matter and basal ganglia abnormalities.3,4 We report 2 young patients in whom MR imaging predominantly showed evidence of globus pallidum paramagnetic ion accumulation. Case Reports Case 1This 8-year-old boy presented with developmental delay and recent swallowing difficulties. He was born at term from consanguineous parents. Family history was negative. He started to walk at 2 years of age and had language delay. At 8 years, he had a generalized seizure. Findings of the physical examination were normal with no dysmorphic features or hepatosplenomegaly. Neurologic examination revealed extrapyramidal rigidity and dystonic postures affecting particularly the upper limbs. Speech was severely impaired because of oromandibular dystonia. He was dysmetric and had an ataxic gait. Reflexes were normal. Routine blood tests, ␣-fetoprotein, vitamin E, copper, and ceruloplasmin titers were negative. Metabolic work-up, including blood and urine chromatography of amino acids and urinary organic acids, and peroxysomal function tests, were unremarkable. Fundoscopy findings, visual and brain stem auditory evoked potentials, and nerve conduction velocity were normal, whereas electromyography disclosed mild neurogenic abnormalities. Electroencephalography showed nonspecific bilateral occipitotemporal slow waves. Lysosomal enzyme assay in cultured skin fibroblasts revealed a ␤-galactosidase activity of 5.8 nmol/mg/h (normal mean, 145 Ϯ 32 nmol/mg/h). Spine x-rays revea...

Sustained Normalization of Neurological Disease after Intracranial Gene Therapy in a Feline Model

“…4A). Of 4 cats treated with the one-tenth dose, 2 reached the humane endpoint at 14.2 and 19.1 months old, 1 was euthanized at 13.9 months old due to chronic weight loss and lethargy, and 1 was euthanized at 21.2 months due to dysphagia, also reported in juvenile-onset GM1 patients (29). Nevertheless, mean survival of the tenth dose cohort was 2.1 times greater than untreated GM1 cats ( P = 0.0012).…”

GM1 Gangliosidosis, Late Infantile Onset Dystonia, and T2 Hypointensity in the Globus Pallidus and Substantia Nigra

“…Two patients reported by De Grandis et al [6] had dysostosis: one had dystonia and ataxia and the other dystonia and spasticity, apparently also of childhood onset, but dysmorphism was not reported. Their genotype was not reported.…”

“…There may also be overlap between GM1 gangliosidosis and Morquio phenotypes [1][2][3]. Neuroimaging in GM1 gangliosidosis has been reported in a limited number of patients [2,[4][5][6].…”

MRI/MRS as a surrogate marker for clinical progression in GM1 gangliosidosis

“…The type is denoted as infantile (I), juvenile (J), or adult (A). Reference number (1) [Ong et al, 2012], (2) [Steenweg et al, 2010], (3) , (4) [Erol et al, 2006], (5) [van der Voorn et al, 2005], (6) [Di Rocco et al, 2005], (7) [Lin et al, 2000], (8) [Al-Essa et al, 1999], (9) [Shen et al, 1998], (10) [Chen et al, 1998], (11) [Kobayashi and Takashima, 1994], (12) [De Grandis et al, 2009], (13) [Vieira et al, 2013], (14) [ Roze et al, 2005], (15) [Campdelacreu et al, 2002], (16) [Tanaka et al, 1995], (17) , (18) [Nardocci et al, 1993], (19) [Inui et al, 1990].…”

“…Only two publications describe imaging in three Type II GM1 gangliosidosis patients. Hypointensity of the globus pallidus, hyperintensity of the putamen, and iron deposition were noted in both reports [De Grandis et al, 2009;Vieira et al, 2013], while atrophy was noted in one [De Grandis et al, 2009]. A third article described MRI findings, however, the type of GM1 gangliosidosis was difficult to classify, based on the description given [Muthane et al, 2004].…”