Table 1.

The main clinical hallmarks and symptoms in gangliosidoses

Disease	Manifestation	Regular symptoms/signs	Facultative symptoms/signs	Remarks
GM1-gangliosidosis	Infantilea,b	Dysmorphic face, severe dysostosis, hepatomegaly, unable to sit, muscle hypotonia, later on spasticity, visual failure, foam cells in bone marrow, oligosacchariduria, mucopolysacchariduria	Cherry-red macular spotc, nystagmus, seizures, splenomegaly, joint contractures, hematologic signs, vacuolated blood lymphocytesd	Rapid or 1–2 year downhill course with psychomotor deterioration, general dystrophy, feeding problems
	Juvenilea	By 4 years or later: dysarthria, extrapyramidal signs including dystonia	Slight intellectual impairment, mild bone changes, foam cells in bone marrow	Some patients have also parts or attenuated forms of the symptoms listed for the infantile disease, other patients belong to the chronic group
	Adulta	As in juvenile disease, but with more insidious onset	Psychosis	Disease is chronic rather than with only adult manifestation
	Chronic			Combines late infantile, juvenile, and sometimes adult manifestations in which the above listed symptoms are partly or gradually developed
GM2-gangliosidosis, variants B, B1 and 0	Infantilee	Loss of head/trunk control, smiling, by about 6 months, cherry-red macular spotc, high startle response to noise, muscle hypotonia by 1 year, epilepsy, tetraparesis with some spasticity, dementia, blindness	Megalencephaly, visceral involvement and oligosacchariduria only in variant 0	Downhill course mostly less rapid than in early GM1-gangliosidosis
	Juvenile/subacute	Onset by 3 to 6 years, dysarthria, loss of speech, spastic paraparesis, later on paraplegyf, pyramidal signsf, cerebellar ataxia, mental deterioration	Seizures, irritability, psychiatric signs, denervation muscle atrophy (EMG), areflexia, cherry red macular spotc	Clinical variability even in siblingsg, above remark to juvenile GM1-gangliosidosis here also apt
	Adult	Clumsiness, lower motor neuron disease, denervation muscle atrophy, cerebellar ataxia	Psychosis	High clinical variability, oldest patient was 76 years
	Chronic			See remark to chronic GM1-gangliosidosis
GM2-gangliosidosis, variant AB		Most as in variants B, B1, 0	Cherry red macular spotc	No adult patients known

^aGrouping of GM1-gangliosidosis patients as type I, II, and III of the disease according to the age at clinical onset is questionable by the often ambiguous onset or insidious or chronic manifestation through all, except the early infantile, age groups (Lyon et al, 1996b).

^bEarlier named “generalized gangliosidosis.”

^cSee Fig. 2D.

^dSee Fig. 2E.

^eEarlier named “infantile amaurotic idiocy”; relatively high prevalence of variant B (Tay–Sachs disease) in Ashkenazim.

^fSee Fig. 2A.

^gMany patients are Ashkenazim, but a genetic isolate of variant B1 is in Spain.