Fabry Disease - Dr. Dina Ibrahim Sallam MNDU 8

3. It Is Named:
 ANGIOKERATOMA CORPORIS
DIFFUSUM.
 ANDERSON-FABRY DISEASE.
 HEREDITARY DYSTOPIC LIPIDOSIS.
 ALPHA-GALACTOSIDASE (A) DEFICIENCY.
(Germain DP. Orphanet J Rare Dis 2010;

4. The second most prevalent
lysosomal storage disorder after
Gaucher disease.
It is an X-linked inborn error of the
glycosphingolipid metabolism resulting from
deficient or absent activity of alpha-galactosidase
A.
Accumulation of globotriaoslyceramide (Gb3) and
related glycosphingolipids in tissues and organs
throughout the body account for clinical
manifestations.
(Germain DP. Orphanet J Rare Dis 2010; 5:30).

5. The prevalence
1:17,000
Seen across all ethnic and
racial groups.
The prevalence is underestimated given
incomplete ascertainment.
Caucasian
1:117,000

6. (Houge G and Skarbøvik AJ. Tidsskr Nor
Laegeforen 2005; 125:1004).
Because the
manifestations of the
disease are nonspecific.
The wrong diagnosis is often
made initially.
The diagnosis is often not considered
by clinicians, given the rarity of the
disease.

8. Any male or female with :
●Intermittent episodes of neuropathic pain.
●Angiokeratomas.
●Hypohydrosis.
●Left ventricular hypertrophy, Stroke & CKD of
unknown etiology in young adulthood.
●Multiple renal sinus cysts discovered incidentally.
(Cho ME, and Kopp JB. Pediatr Nephrol 2004; 19:583).

10. Globotriaosylceramide
Gb3

12. GLOMERULI
PODOCYTES
ENDOTHELIA
CELLS
MESANGIAL
CELLS
GB3
PROTENURIA ESRD
DISTAL
TUBULES
POLYUREA &
POLYDEPSIA
Najafian B. et al., Kidney Int.
2011;79(6):663.

14. Neuropathic
pain
75% 10 years
Telangiectasias and
angiokeratomas 70% 17 years
Renal
manifestation 80% 35_40
years
Cardiac
manifestation
80% 42 years
Others: GIT symptoms
, hypohydrosis, eye, ear
manifestation, heat & cold
intolerance.
50_70%
4th
decade
Cerebrovascular &
neuronal manifestation. 25% 42 years

16. Present history
Past history
Family
history
General
Local
DETAILED
HISTORY
EXAMINATION

17. Established family history
and classic phenotype:
Diagnosis in females or males
with atypical presentation:
Borderline
Results:
Gene
Study.
Enzyme assay
(Leucocyte or plasma).
INVESTIGATIONS
(Germain DP. Orphanet J Rare Dis 2010;

18. (Mauer. M uptodate 2015).
Uniform recommendations for the
use of enzyme replacement therapy
(ERT), definitive timing of its start
and duration do not exist.

19. (Najafian B, et al. Kidney Int 2011; 79:663).

20. (Eng CM, et al. , N Engl J Med 2001; 345:9).
Agalsidase beta
(Fabrazyme)
1 mg/kg IVI / 2 wks.
Extremely expensive, the
estimated cost of therapy for one
year was about $200,000 in
Europe and the United States.
Agalsidase alfa
(Replagal)
0.2 mg/kg IVI / 2 wks.
Types of ERT

21. Clear deposits
moderately from
vascular smooth
muscle.
Significant
reduction of
deposition
(Gb3).
Improve GIT
manifestations.
(El Dib RP.,et al., Cochrane Database Syst Rev
2013; 2).
*Clears deposits from
glomerular endothelial,
mesangial and interstitial
cells.
*No significant effect on
Podocytes, distal tubules
and arterial smooth muscle
cells.
Significantly
Reduces the
neuropathic
pain.
Value of
E.R.T.

22. Effect of E.R.T. On
KINDEY diseases:
 CKD stage 1-2:
Significantly reduce rate of deterioration of kidney
function.
 CKD 3-5 and Dialysis patients: Of limited
value as it does not fully clear Gb3 deposits from
Podocytes, only improves neuronal and cardiac
manifestations.
 Transplanted kidney: Reduces renal
deposition of GB3 coming from the high systemic
load that exceeds the renal clearance capacity.Tøndel C. et al., J Am Soc Nephrol 2013;
24:137.
Terryn W. et al., Nephrol Dial
Transplant.2013;28(3):505.

23. Renal
Transplantation
Shah T. et al., Transplantation.
 Five- and ten - year graft survival
were similar in patients with Fabry disease and
those
with other causes of ESRD.
 Without ERT, deposits are shown to Reappear
but late & insufficient to compromise allograft
function.
 Causes of death in transplanted patients with
Fabry are due to cardiovascular and neuronal
complications.
 Renal transplantation with ERT is much more
superior than transplantation only.

24. Conclusion:
 Fabry disease is not uncommon disease
.
 Diagnosis needs a high index of
suspicion.
 Screening of family member of affected
patient is important.
 Start enzyme replacement therapy as
soon as renal manifestations appear.
 Treat female carrier once has