Environmental Engineering Reference
In-Depth Information
most severe form of the disease (i.e. neonatal Gaucher disease infants die in utero or
shortly after birth), whereas a later onset mainly of peripheral symptoms is char-
acteristic for milder adult forms (i.e. heterozygous female Fabry patients who may
remain asymptomatic throughout life). Juvenile forms are intermediate between
infantile and adult forms.
Many of the conditions show significant similarities. Progressive central nervous
system impairment, with or without systemic involvement, represents by far one of
the most devastating aspects of LSDs and also one of the most difficult disease to
treat. The incidence of central nervous system (CNS) involvement is about 60-
70 % in all LSDs [
43
]. CNS disease can result in developmental delay, mild-to-
severe mental retardation, seizures and profound neurodegeneration. Seizures were
found in oligosaccharidoses and sphingolipidoses, while in mucopolisachharidoses
were not reported. Severe seizures are frequently associated with a rapid mental
decline, which in 1-2 years leads to the vegetative state. Another feature of LSDs is
the visceromegaly. Splenomegaly, especially hepatosplenomegaly, is the hallmark
of lysosomal storage diseases. Heart diseases are also commonly present in LSDs.
Reddish purple cutaneous vascular lesions, known as angiokeratomas, are also
characteristics for some LSDs, most often encountered in Fabry disease. They are
primarily distributed on the buttocks, groin, umbilicus and upper thighs and become
larger and more numerous with age.
A number of other clinical manifestations are specific to certain diseases, such
as: optic atrophy seen in Krabbe disease, retinopathy characteristic for
mucolipidoses type II (i-cell disease), supranuclear ophthalmoplegia (pain in eye
movement) common in type II and III of Niemann-Pick disease, ichthyosis have
been reported in multiple sulfatase deficiency, while proteinuria and chronic renal
failure is distinctive for Fabry disease. Aggressive behavior is prominent in
mucopolisaccharidoses type II (Hunter disease), type III (Sanfilippo disease) and
alpha-fucosidosis.
Most LSDs are autosomal recessive disease, which means that their transmission
and manifestation requires the presence of two copies of the same altered gene, one
copy from each parent; in the case of heterozygotes (carrier-individuals with a
single malfunctioning gene copy), the enzyme activity generated by their other
(normal) allele is often sufficient, so they do not exhibit evidence of tissue storage.
Exceptions are Fabry, Hunter and Danon diseases which are X-linked heterosomal
recessive disorders. While for carrier females of Hunter
s syndrome, clinical
problems related to the presence of an altered protein are not evident, this is not
the case of most of the females who are carriers of Fabry
'
s diseases. The
last ones may experience disease-related complications, which in a few cases can be
as severe as those found in classically affected males.
Although lysosomal storage diseases are considered as a group of rare diseases,
their combined prevalence is between 1:5,000 and 1:8,000 [
44
,
45
]. This relatively
high incidence caused investigations regarding the feasibility of several screening
methods for these diseases [
46
,
47
]. Necessity of screening methods emerge from:
(1) the high frequency of certain diseases among a particular ethnic group
(i.e. Gaucher, Tay-Sachs and Niemann-Pick diseases are common among
s or Danon
'
'
