Abstract
GM2-gangliosidosis, AB variant is a very rare form of GM2 gangliosidosis due to a deficiency of GM2 activator protein, associated with autosomal recessive mutations in GM2A. Less than ten patients, confirmed by molecular analysis, have been described in the literature.
A 12-month-old Hmong girl presented to the neurometabolic clinic for evaluation of global developmental delay, hypotonia, and cherry red spots. The parents were not known to be consanguineous. Her examination was remarkable for hypotonia with hyperreflexia and excessive startling. The head circumference was normal. An extensive neurometabolic evaluation was negative.
Developmental regression began at 14 months of age. Retinal examination at 16 months of age disclosed 4+ cherry red/black spots with “heaped up” ring of whitish infiltrate surrounding both foveae but no evidence of optic atrophy or peripheral retinal abnormalities. Repeat magnetic resonance imaging (MRI) scan at 17 months of age revealed delayed but interval myelination associated with abnormal signal intensity of the bilateral thalami presenting as T2 hyperintensity of the posterior thalami in the region of the pulvinar nuclei and T2 hypointensity in the anterior thalami. Sequencing of the GM2A gene revealed a homozygous c.160 G>T mutation, predicted to result in a premature protein termination p. Glu54*.
Competing interests: None declared
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Communicated by: Nicole Wolf, MD PhD
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Take-Home Message
Typical clinical symptoms and MRI findings associated with cherry red spots in the setting of normal beta-hexosaminidase A activity should lead to sequencing of GM2A for AB variant, a rare, but underdiagnosed, form of GM2 gangliosidosis.
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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.
Author Contributions
Deborah L. Renaud, M.D., is the primary author and corresponding author.
Michael Brodsky, M.D., contributed to the writing and editing of the manuscript and provided Fig. 1.
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Renaud, D., Brodsky, M. (2015). GM2-Gangliosidosis, AB Variant: Clinical, Ophthalmological, MRI, and Molecular Findings. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 25. JIMD Reports, vol 25. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2015_469
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DOI: https://doi.org/10.1007/8904_2015_469
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