G M1 Gangliosidosis Type 2 in Two Siblings

Abstract

A sister and brother, now aged 7 and 9 years, presented with developmental arrest, gait disturbance, dementia, and a progressive myoclonic epilepsy syndrome with hyperacusis in the second year of life. Then, spastic quadriparesis led to a decerebrate state. In the absence of macular or retinal degeneration, organomegaly, and somatic-facial features suggesting mucopolysaccharidosis, the presence of hyperacusis together with sea-blue histiocytes in bone marrow biopsies and deficient beta-galactosidase activity but normal glucosidase, hexosaminidase, and neuraminidase activity on lysosomal enzyme assays constitutes the clinical-pathologic-biochemical profile of GM1 gangliosidosis type 2. This is a rare, late infantile onset, progressive gray-matter disease in which beta-galactosidase deficiency is largely localized to the brain, though it can be demonstrated in leukocytes and cultured skin fibroblasts. It must be distinguished from the Jansky-Bielschowsky presentation of neuronal ceroid lipofuscinosis, mitochondrial encephalopathy, lactic acidosis, strokelike episodes (MELAS) and myoclonic epilepsy with ragged-red fibers (MERRF) syndromes, atypical presentations of GM2 gangliosidoses (Tay-Sachs and Sandhoff's diseases), primary sialidosis (neuraminidase deficiency), galactosialidosis, and Alpers' disease.

Brain Proton Magnetic Resonance Spectroscopy and Neuromuscular Pathology in a Patient With GM1 Gangliosidosis

“…[9][10][11][12][13][14] In our patient, the brain MRI showed the typical diffuse and severe reduction of myelination in the central white matter and increased T2-weighted signal in the thalami and basal ganglia ( Figure 1A, B). [10][11][12][13] It also showed a lack of myelination in the central aspect of the cerebellar hemispheres on T2-weighted images and a diffusely and severely thinned corpus callosum.…”

“…[9][10][11][12][13][14] In our patient, the brain MRI showed the typical diffuse and severe reduction of myelination in the central white matter and increased T2-weighted signal in the thalami and basal ganglia ( Figure 1A, B). [10][11][12][13] It also showed a lack of myelination in the central aspect of the cerebellar hemispheres on T2-weighted images and a diffusely and severely thinned corpus callosum. Cerebellar involvement was previously reported in only 1 patient described by Di Rocco et al 13 A characteristic pattern of radial stripes of low signal intensity within the hyperintense white matter has also been observed in a single case of GM 1 gangliosidosis, as well as other lysosomal storage disorders (ie, metachromatic leukodystrophy and Krabbe disease).…”

Pathogenic role of ganglioside metabolism in neurodegenerative diseases

“…GM1 gangliosidosis is an autosomal recessive disease caused by a deficiency of lysosomal β‐galactosidase. GM1 gangliosidosis is a progressive neurodegenerative disease with three clinical subtypes: infantile (type 1), juvenile (type 2), and adult‐onset (type 3; Beratis et al, ; Suzuki and Vanier, ; Gascon et al, ) variants. In type 1, motor and mental retardation progress most rapidly and resemble the features of a neurolipidosis and mucopolysaccharidosis (i.e., neurodegeneration, progressive organomegaly, dysostosis, coarsened facial features, and multiplex macular cherry‐red spots).…”

Case series of two siblings suffering from GM1 gangliosidosis resulting in early multiple joint arthroplasties

“…GM1 gangliosidosis results from the deficiency of beta-galactosidase enzyme, which hydrolyzes the terminal beta-galactosyl residues from GM1 ganglioside glycoprotein and glycosaminoglycans [3]. Diagnostic blood tests demonstrate a deficiency of beta galactosidase in brain cells, leukocytes and cultured skin fibroblasts [4,5].…”

“…Gaucher disease, the most common lysosomal storage disorder, is associated with chronic inflammation resulting in microvascular occlusions including avascular necrosis [6,7]. GM1 gangliosidosis is divided into three categoriestype 1(the most severe): affecting the early infantile population leading to an early death of the patients, type 2: affecting the late infantile population (1-3 years) [5] and type 3: affecting the child from age 3 onwards up to 41 years [2]. The condition affects the central nervous system predominantly and the musculoskeletal system.…”