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*.
Global Developmental Delay Abnormal Signal Intensity Sandhoff Disease Repeat Magnetic Resonance Imaging Anterior Thalamus
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.
Chen B, Rigat B et al (1999) Structure of the GM2A gene: identification of an exon 2 nonsense mutation and a naturally occurring transcript with an in-frame deletion of exon 2. Am J Hum Genet 65(1):77–87CrossRefPubMedPubMedCentralGoogle Scholar
Gravel R, Kaback MM et al (2014) The GM2 Gangliosidoses. In: Valle D, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G (eds) OMMBID. McGraw-Hill, New YorkGoogle Scholar
Schepers U, Glombitza G et al (1996) Molecular analysis of a GM2-activator deficiency in two patients with GM2-gangliosidosis AB variant. Am J Hum Genet 59(5):1048–1056PubMedPubMedCentralGoogle Scholar
Schroder M, Schnabel D et al (1991) A mutation in the gene of a glycolipid-binding protein (GM2 activator) that causes GM2-gangliosidosis variant AB. FEBS Lett 290(1-2):1–3CrossRefPubMedGoogle Scholar
Schroder M, Schnabel D et al (1993) Molecular genetics of GM2-gangliosidosis AB variant: a novel mutation and expression in BHK cells. Hum Genet 92(5):437–440CrossRefPubMedGoogle Scholar
Smith NJ, Winstone AM et al (2012) GM2 gangliosidosis in a UK study of children with progressive neurodegeneration: 73 cases reviewed. Dev Med Child Neurol 54(2):176–182CrossRefPubMedGoogle Scholar
Xie B, Wang W et al (1992) A Cys138-to-Arg substitution in the GM2 activator protein is associated with the AB variant form of GM2 gangliosidosis. Am J Hum Genet 50(5):1046–1052PubMedPubMedCentralGoogle Scholar