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RARE DISEASES
is 0.04 g. An echocardiogram
revealed an ejection fraction
of 66% and no left ventricular
hypertrophy. She has recently
developed angiokeratomas and
a peripheral neuropathy.
The pedigree analysis
(Figure 3) and follow up reveals
that the recipient’s brother also
suffers from Fabry disease.
Both brothers’ children, all
daughters, have also been
diagnosed. The recipient’s son
has been diagnosed as well.
The remaining siblings were
Figure 1: 24 hour protein/units in grams
Figure 2: 24 creatinine clearance/units in ml/min
Figure 3: The pedigree analysis
Figure 4: Fabry disease progression
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unaffected. The mother of both
patients was found to be the
carrier. Three other extended
family members have also been
diagnosed. The average cohort
of family members diagnosed
with Fabry disease is around
five. Thus far, 10 members of
this family have been diagnosed
with Fabry disease.
Discussion
Fabry disease is a lysosomal
storage disorder. It is the second
most prevalent lysosomal
storage disorder after Gaucher
disease. It is inherited as an
X-linked inborn error of the
glycosphingolipid metabolic
pathway. This is a multisystem
progressive disease, which is
devastating if untreated.
The disease transmitted by
the X chromosome. Daughters,
however, can be carriers or be
affected. If a female is affected,
then 50% of her children
manifest disease. Affected sons
will show overt manifestation
of the disease.
It is a pan-ethnic disorder
and the prevalence is under-
estimated due to incorrect
diagnosis or delayed
diagnosis. The prevalence
of Fabry disease is probably
underestimated given
incomplete ascertainment
and the manifestations of the
disease being nonspecific.
The diagnosis is often not
considered by clinicians, given
the rarity of the disease.
In the Fabry Outcome Survey,
the mean delay to correct
diagnosis after symptom
onset was estimated to be 13.7
and 16.3 years for males and
females, respectively.
The symptoms of Fabry
disease tend to appear in a
predictable order in classically
affected males (Figure 4).
They begin in childhood or
adolescence and include severe
neuropathic or limb pain, which
may be precipitated by stress,
extremes of heat or cold and
physical exertion.
Neuropathic symptoms
occur in more than 75 percent
of patients with a mean age
of onset of 10 years. Renal
disease occurs before CNS and
vascular disease.
The morbidity and
eventual mortality is
seen either manifesting
through renal, cardiac or
cerebrovascular disease.
When to suspect
Fabry disease:
» Acroparesthesias
» Angiokeratomas
» Hypohidrosis
» Left ventricular hypertrophy
of unknown etiology
» Stroke of unknown etiology
» Chronic kidney disease of
unknown aetiology
» Multiple renal sinus cysts.
» Family history of premature
death.
Commonly mistaken
diagnosis
» Rheumatoid arthritis due
to pain in the joints and
elevated ESR.
» Erythromelalgia associated
with painful extremities.
» Raynaud’s syndrome causing
pain and sensitvity in the
extremities
» Multiple sclerosis responsible
for stroke-like events in the
brain stem structures.
Inherited kidney disease is
under-diagnosed and not well
screened for. Screening the
family essential in of those
patients who have unexplained
renal failure. There is also
a need for pre-transplant
evaluation for Fabry disease or
other inherited kidney disease
in unexplained end stage renal
disease, especially if a family
history is present.
Although Fabry disease
is considered ‘rare’, its
inheritance, genetics,
pathophysiology and systemic
manifestations are very well
understood. The treatment with
enzyme replacement therapy
reflects a clear understanding
of the disorder and newer
therapies being investigated
provide a reflection of the vast
knowledge surrounding the
disease process of this storage
disorder. SF
The Specialist Forum | Vol. 17 No. 4