Short Communication Late onset GM2 gangliosidosis mimicking spinal muscular atrophy Z. Jamrozik a, ⁎, A. Ługowska b , M. Gołębiowski c , L. Królicki d , J. Mączewska d , M. Kuźma-Kozakiewicz a a Department of Neurology, Medical University of Warsaw, Poland b Department of Genetics, Institute of Psychiatry and Neurology, Warsaw, Poland c Department of Radiology, Medical University of Warsaw, Poland d Department of Nuclear Medicine, Medical University of Warsaw, Poland abstract article info Article history: Accepted 4 June 2013 Available online 29 June 2013 Keywords: Late onset GM2 ganglisidosis Motor neuron disease Spinal muscular atrophy HEXA gene A case of late onset GM2 gangliosidodis with spinal muscular atrophy phenotype followed by cerebellar and extrapyramidal symptoms is presented. Genetic analysis revealed compound heterozygous mutation in exon 10 of the HEXA gene. Patient has normal intelligence and emotional reactivity. Neuroimaging tests of the brain showed only cerebellar atrophy consistent with MR spectroscopy (MRS) abnormalities. (18) F-fluorodeoxyglucose positron emission tomography (18)F-FDG PET/CT of the brain revealed glucose hypometabolism in cerebellum and in temporal and occipital lobes bilaterally. © 2013 Elsevier B.V. All rights reserved. 1. Introduction The GM2 gangliosidoses (GM2G) are a group of rare metabolic diseases, inherited in autosomal recessive fashion. They are charac- terized by lysosomal storage of ganglioside GM2 and related gangliosphingolipids in neurons and glial cells. There are three vari- ants of GM2 gangliosidoses: Tay–Sachs disease (TSD), Sandhoff dis- ease, and GM2 activator deficiency. TSD is caused by a deficient activity of a lysosomal hydrolase — hexosaminidase A (Hex A). This enzyme is composed of two subunits, called alpha and beta (αβ structure). The alpha subunit of Hex A is coded for by the HEXA gene located on chromosome 15q23. The beta subunit of Hex A is encoded by the HEXB gene located on chro- mosome 5q13.3. TSD results only from mutations in the HEXA gene (GM2 gangliosidosis type B; GM2-B). Sandhoff disease is caused by deficient activities of both hexosamin- idase A and hexosaminidase B (Hex B). Hex B is composed of two beta subunits (ββ structure). Thus, Sandhoff disease results from mutations in the HEXB gene (GM2 gangliosidosis type 0; GM2-0). There is also a third variant of GM2 gangliosidosis caused by the lack of functional protein — GM2 activator, which is coded for by the GM2A gene located on chromosome 5q33.1. Total lack of enzymatic activity is typical of severe forms of Tay– Sachs disease or Sandhoff disease. Partial enzymatic deficiency is char- acteristic of late-onset or chronic GM2 gangliosidoses (LOGM2). This consists of juvenile and adult forms. Adult forms of TSD with residual Hex A activity are usually found in compound heterozygotes for, most often, p.G269S mutation and another mutation in the HEXA gene and they are characterized by genetic heterogeneity (Navon, 1991). Late onset GM2G exhibits a wide range of symptoms including cerebellar ataxia, dystonia, anterior motor neuron disease, psychiatric symptoms, dementia and rarely polyneuropathy (Hund et al., 1997). We describe an adult patient presenting with LOGM2, with long his- tory mimicking spinal muscular atrophy, who after nine years devel- oped extrapyramidal and cerebellar syndrome without dementia. 2. Case report The patient is a male of Caucasian origin who developed muscle atrophy in the lower limbs at the age of 30. Gene 527 (2013) 679–682 Abbreviations: MRI, magnetic resonance imaging; MRS, magnetic resonance spectros- copy; MRS (SVS), magnetic resonance spectroscopy single voxel; (18)F-FDG PET CT, (18) F-fluorodeoxyglucose positron emission tomography; FDG-PET, fluorodeoxyglucose positron emission tomography; GM2G, GM2 gangliosidoses; GM2-B, GM2 gangliosidosis type B; GM2-0, GM2 gangliosidosis type 0; LOGM2, late-onset or chronic GM2 gangliosidoses; Hex A, hexosaminidase A; Hex B, hexosaminidase B; mI/Cr, myo- inositol/creatine; NAA/Cr, ratio of the N-acetylaspartate/creatine; SMA, spinal muscular atrophy; TSD, Tay–Sachs disease; TE, time echo; MLPA, multiplex ligation-dependent probe amplification; ALS, amyotrophic lateral sclerosis; MND, motor neuron disease; TSE, time spin echo. ⁎ Corresponding author at: Department of Neurology Medical University of Warsaw, Banacha 1 a Str., 02-093 Warsaw, Poland. Tel.: + 48 22 5992773; fax: + 48 22 5991857. E-mail address: zygmunt.jamrozik@wum.edu.pl (Z. Jamrozik). Table 1 Lysosomal enzyme activities in isolated blood leucocytes. Enzyme Activity Units Mean controls β-Galactosidase (control enzyme) 150 nmol/mg protein/h 166 ± 99 Hexosaminidase A + B 330 nmol/mg protein/h 746 ± 241 % of the Hex A thermolabile form 7 % 54 ± 7 Hex A (activity measured with sulfated substrate) 5 nmol/mg protein/h 149 ± 53 0378-1119/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.gene.2013.06.030 Contents lists available at SciVerse ScienceDirect Gene journal homepage: www.elsevier.com/locate/gene