Chemistry Reference
In-Depth Information
Table 30.1
Forms of gangliosidosis and corresponding pathology.
Type
Defective gene
Pathology
GM2 gangliosidosis
B variant (Tay - Sachs)
α
- subunit of HexA (
α
β
) and
Massive storage of GM2 and GA2 in grey and
white matter; severity correlates inversely with
residual activity of HexA; occurs as infantile
(classical Tay-Sachs, fatal), juvenile and adult
forms
S (
); more than 50 different
mutations
α
α
B1 variant
α
- subunit of HexA (
α
β
) and
Mutated HexA active toward uncharged sub-
strates (GA2) but not toward GM2, which is
stored; a juvenile disease progression
S(
α
α
) 3 mutations at Arg178
O variant (Sandhoff )
β
- subunit of HexA (
α
β
) and
Storage of GM2, GA2 and globoside throughout
the CNS; also in visceral organs; pathology and
symptoms similar to B-variant
Hex B (
β
β
)
AB variant
GM2 activator
Comparable to B variant; symptom appearances
slightly delayed
GM1 gangliosidosis
Type 1 (infantile)
GM1 -
β
- galactosidase
Storage of GM1 and GA1 in visceral organs and
brain, progressive motor and mental retardation,
short lifespan.
Type 2 (late infantile)
Similar to type 1, but less severe, with lifespan
about 10 years.
GM1 -
β
- galactosidase
Type 3 (adult)
Mild and slowly progressive neurological symp-
toms.
GM1 -
β
- galactosidase
Morquio type B
Skeletal deformation without involvement of the
CNS; oligosaccharides with terminal galactose
accumulate in viscera
GM1 -
β
- galactosidase
Lysosomal storage diseases that result from genetic defects in
- galactosi-
dase are indicated with corresponding pathological and clinical symptoms. Many mutations have been discovered
in some, with varying effects on enzyme activities.
β
-hexosaminidase (HexA and B) and
β
-Hexosaminidase S is involved in degradation of GAGs. GM2
activator is a glycoprotein that is a necessary cofactor for
β
-hexosaminidase. GA1 and GA2 refer to uncharged
asialo - GM1 and asialo -GM2, respectively. Please see also Info Box in Chapter 11 .
β
is the primary sialidase of lysosomes, but can also appear on the cell surface in
some situations, while Neu2 is cytosolic. The locus and function of Neu4 are not
yet known. In addition to converting gangliotetraose gangliosides to GM1, these
enzymes also hydrolyze such structures as GM4, GM3, GD3 and o- series ganglio-
sides to neutral GSL products.
30.4
Gangliosides of the Peripheral Nervous System
The PNS has not been studied as intensively as the CNS in relation to GSL
composition, but both sensory and motor nerves are known to contain the four
