IllnessGM2-Gangliosidosis, differential diagnosis

NGS +

Classical Tay-Sachs disease is characterized by progressive weakness, loss of motor skills from 3-6 months, decreased attention and startle response in addition to the cherry red spot in the retina, followed by loss of previous skills after about nine months. Seizures predominate at the age of one year, with continuing deterioration in the second year and death between 2-3 years (rarely surviving up to 5-7 years possible). The subacute juvenile Tay-Sachs disease is associated with normal development until the age of two years, when gait disorders and dysarthria begin, acquired abilities and cognition decrease. Spasticity, dysphagia and seizures are observed after the age of 10, with death occurring after a few more years. Late onset forms occur in adolescents or young adults with progressive neurological symptoms including psychosis. Clinical variability is evident even among affected members of the same family in subacute adolescents and late onset phenotypes. The clinical phenotype of the AB variant is very similar to the classical M. Tay-Sachs. In addtion, M. Sandhoff is also a progressive neurodegenerative disease caused by accumulation of GM2 gangliosides in neurons. M. Sandhoff is clinically practically indistinguishable from the subacute form of Tay-Sachs. M. Tay-Sachs, M. Sandhoff and the GM2 gangliosidosis AB variant are inherited autosomal recessively.

The clinical sensitivity, specificity and positive predictive value of DNA analysis are close to 100% and always significantly higher than enzymatic tests. An inconspicuous genetic finding means a practically certain exclusion of the clinical suspected diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1218/

• Alias: GM2 activator deficiency (GM2)
• Alias: GM2-gangliosidosis, AB variant (Tay-Sachs disease, AB variant)
• Allelic: Lewy body dementia, susceptibility to (GBA)
• Allelic: Macular dystrophy with central cone involvement (MFSD8)
• Allelic: Parkinson disease, late-onset, susceptibility to (GBA)
• Allelic: Spinocerebellar ataxia, AR 7 (TPP1)
• Alexander disease (GFAP)
• Canavan disease (ASPA)
• Ceroid lipofuscinosis, neuronal, 1 (PPT1)
• Ceroid lipofuscinosis, neuronal, 10 (CTSD)
• Ceroid lipofuscinosis, neuronal, 2 (TPP1)
• Ceroid lipofuscinosis, neuronal, 5 (CLN5)
• Ceroid lipofuscinosis, neuronal, 6A (CLN6)
• Ceroid lipofuscinosis, neuronal, 6B, Kufs type (CLN6)
• Ceroid lipofuscinosis, neuronal, 7 (MFSD8)
• Ceroid lipofuscinosis, neuronal, 8 (CLN8)
• Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant (CLN8)
• GM1-gangliosidosis, type I, II, III (GLB1)
• GM2-gangliosidosis, several forms (HEXA)
• Galactosialidosis (CTSA)
• Gaucher disease, perinatal lethal (GBA)
• Gaucher disease, type I, II, III, IIIC (GBA)
• Hex A pseudodeficiency (HEXA)
• Hexosaminidase activator deficiency (GM2)
• Krabbe disease (GALC))
• Mucolipidosis II, III alpha/beta (GNPTAB)
• Mucopolysaccharidosis type IVB, Morquio (GLB1)
• Niemann-Pick disease, type A, B (SMPD1)
• Sandhoff disease, infantile, juvenile + adult forms (HEXB)
• Sialidosis, type I, II (NEU1)
• Tay-Sachs disease (HEXA)