Lysosomes are sub cellular organelles
responsible for the physiologic turnover of
The lysosomes is commonly referred to as
cell’s recycling centers.
They contain catabolic enzymes,
which require a low pH environment in
order to function optimally.
If one of these catabolic enzymes is
defective, because of a mutation, large
molecules accumulate within the cell,
eventually killing it.
Lysosomal storage diseases describe a
heterogeneous group of rare inherited
disorders characterized by the
accumulation of undigested or
partially digested macromolecules,
which results in cellular dysfunction
and clinical abnormalities.
Lysosomal storage disorders are
caused by lysosomal dysfunction
usually as a consequence of deficiency
of a single enzyme required for the
metabolism of lipids, glycoproteins
(sugar containing proteins) or so-called
Classically, lysosomal storage diseases
encompassed only enzyme
deficiencies of the lysosomal
More recently, the concept of
lysosomal storage disease has been
Recent concept : include deficiencies or
defects in proteins necessary for the normal
post-translational modification of lysosomal
enzymes (which themselves are often
glycoproteins), activator proteins, or proteins
important for proper intracellular trafficking
between the lysosome and other intracellular
Lysosomal storage diseases are generally classified
by the accumulated substrate and include the
mucolipidoses, mucopolysaccharidoses (MPSs),
lipoprotein storage disorders, lysosomal transport
defects, neuronal ceroid lipofuscinosis and others.
Age of onset and clinical manifestations may vary
widely among patients with a given lysosomal
Neuronal ceroid lipofuscinoses (NCL) is the
general name for a family of at least eight
genetically separate neurodegenerative
Lipids are fat-like substances that are
important parts of the membranes found
within and between each cell and in the
myelin sheath that coats and protects the
Autosomal recessive inheritance
X-linked recessive inheritance occurs when
the mother carries the affected gene on the X
chromosome that determines the child’s
Affected men do not pass the disorder to
their sons but their daughters will be carriers
for the disorder.
Fabry disease is an inherited disorder that results from
the buildup of a particular type of fat, called
Fabry DiseaseSynonyms: Anderson-Fabry Disease,
Alpha-Galactosidase A DeficiencyAtul Mehta, MA, MD,
FRCP, FRCPath and Derralynn A Hughes, MA, DPhil,
in the autonomic nervous system, eyes, kidneys, and
Fabry disease affects an estimated 1 in 40,000 to
60,000 males. This disorder also occurs in females,
although less frequently.
Fabry disease is caused by mutations in the GLA
gene. This gene provides instructions for making
an enzyme called alpha-galactosidase A, which
normally breaks down globotriaosylceramide
GLA gene mutations that result in an absence of
alpha-galactosidase A activity lead to the classic,
severe form of Fabry disease. Mutations that
decrease but do not eliminate the enzyme's activity
usually cause the milder, late-onset forms of Fabry
disease that affect only the heart or kidneys.
Diagnosis is made through clinical examination,
biopsy, genetic testing, molecular analysis of cells
or tissues, and enzyme assays (testing a variety of
cells or body fluids for enzyme deficiency).
In some forms of the disorder, a urine analysis can
identify the presence of stored material.
Biopsy for lipid storage disease involves removing
a small sample of the liver or other tissue and
studying it under a microscope
Genetic testing can help individuals who have
a family history of lipid storage disease.
Other genetic tests can determine if a fetus
has the disorder or is a carrier of the
Prenatal testing is usually done by chorionic
villus sampling, in which a very small sample
of the placenta is removed and tested during
Results are usually available within 2 weeks.
One of the first symptoms which often begins
in childhood is a painful burning sensation in
the hands and feet called acroparesthesia.
The pain can be severe and worsen with
exercise, stress, illness, and variations in
Stomach and Intestines
Early gastrointestinal symptoms of Fabry
disease include abdominal cramps, frequent
bowel movements shortly after eating,
diarrhea, and nausea.
A common skin condition associated with Fabry
disease is a red, non-painful rash known as
angiokeratoma. It usually appears in the area
between the belly and the knees, but may also
appear on other parts of the body such as the lips,
tongue, hands, and toes. Additionally, it may be
confined to a small area of the body, or may affect
a larger area
The surface layer of the eye (cornea) may appear
abnormal when examined by an eye specialist
(ophthalmologist). This unique appearance of the cornea
is called cornea verticillata and while it does not affect
vision, it may become more obvious with time. Cornea
verticillata occurs in approximately three-quarters of
patients with Fabry disease and may be a reliable
indicator of the condition.
Most patients with Fabry disease will have
some degree of hearing loss at some point
which can either come on suddenly or
develop over a period of time. Some
individuals experience a ringing in the ears
that is called tinnitus.
Many individuals with Fabry disease experience
kidney problems, commonly beginning in adults
in their mid-30s. Abnormally functioning cells in
the kidney weaken the kidneys' ability to filter
waste from the blood to create urine. When the
kidneys cannot properly filter waste, excess
protein begins to appear in the urine — a
condition know as proteinuria. Over time, kidney
damage may progress to the point that the
kidneys lose some or all ability to function,
requiring dialysis or transplant.
The heart abnormalities often described with
Fabry disease include changes in the size of
the heart (left ventricular enlargement),
irregular heartbeat, and leaky heart valves.
Such problems increase the risk of further
troke like symptoms called transient ischemic
attacks (TIAs) and in some cases, actual
Daily prophylactic doses of neuropathic pain
agents (eg, phenytoin, carbamazepine,
gabapentin, or a combination of these
agents) provide some degree of relief. They
are effective in decreasing the frequency and
severity of pain episodes or pain crises in
most patients.Some patients may require
more potent analgesics (eg, opioids) for pain
No specific treatment has been found to
control GI symptoms in Fabry disease.
However, pancrelipase, metoclopramide, H2
blockers, loperamide, and hydrochloride can
ameliorate GI symptoms in some
patients.Patients with abdominal symptoms
often benefit from a change in eating habits
that includes frequent small meals.
The results of various laser methods used to
treat angiokeratomas in patients with Fabry
disease have not been promising for patients
who are not receiving enzyme replacement
Lesions may be treated with a series of liquid
nitrogen treatments prior to laser therapy.
Ocular symptoms in patients with Fabry
disease rarely, if ever, cause significant
impairment of vision and, as a rule, do not
Hearing loss can be treated with hearing aids.
Patients should avoid excessive noise