21 - 127 - FABRY DISEASE Flashcards
Fabry disease is a rare X-linked metabolic disorder caused by the partial or complete deficiency of a lysosomal enzyme ________
α-galactosidase A
What glycosphingolipids predominantly accumulates in Fabry disease?
globotriaosylceramide
As a result of this enzyme deficiency, neutral sphingolipids with terminal α-galactosyl residues (predominantly globotriaosylceramide [Gb3]) accumulate in the lysosomes of different tissues and fluids (epithelial cells of glomeruli and tubules of the kidneys; cardiac myocytes; ganglion cells of the autonomic system; cornea; endothelial, perithelial, and smooth muscle cells of blood vessels; and histiocytic and reticular cells of connective tissue).
cutaneous hallmark of Fabry disease
Angiokeratomas
(pinpoint to 4 mm diameter, dark-red to blue-black, macular and papular lesions that do not blanch on pressure)
Angiokeratomas are also seen on the proximal limbs, particularly their medial aspects, the elbows and knees, the palms and soles, and over the distal phalanges of the digits (Fig. 127-4).
Lesions may occur on the lips, particularly along the vermilion border, and occasionally on the mucosal surfaces (Fig. 127-5).
In females, angiokeratomas are usually sparsely distributed (Fig. 127-6), and may occasionally occur in a dermatomal distribution.13 The most common sites are the trunk and proximal limbs. 13 Female genital lesions are relatively infrequent.
Which of the following is true regarding Fabry Disease, except?
a. The cutaneous hallmark of this X – linked metabolic disorder are angiokeratomas. This is present in 70% of males and 39% of females
b. Up to a third of Fabry males and two-thirds of Fabry females hav angiokeratomas
c. Cutaneous vascular lesions is associated with higher disease severity scores
d. Angiokeratomas are seen typically in bathing trunk area of males, while in females these are sparsely distributed and may occasionally occur in a dermatomal distribution.
Answer: B p. 2295 …DO NOT have angiokeratomas
Which enzyme accumulates in the lysosomes of different tissues and fluids in patients with Fabry Disease
a. Alpha- galactosidase A
b. Chondroitin sulfate
c. Globotriaosylceramide
d. Cerebroside
Answer: C – elevated levels of globotriaosylsphingosine accumulate in the lysosomes of diff tissues and fluids a- Deficient lysosomal enzyme
Which of the following is true regarding Fabry Disease
a. Females die in the 4th -5 th decade, while males live perhaps 15 years longer
b. Right ventricular hypertrophy is a common cardiac manifestation of Fabry disease
c. Renal manifestation is a constant feature and increasingly recognized as the major cause of death in both male and female patients
d. Renal manifestations are seen in more
than 90% of males
Answer: D
A. males with fabry disease die in 4-5th decade, females live perhaps 15 years longer p. 2300
B. leFFFt ventricular hypertrophy p. 2299 FFFABRY
C. Cardiac manifestation p. 2299
D. True p. 2299
True/False: Hypohidrosis is a classical feature of Fabry diseases. It is more common in male patients than females, while hyperhidrosis occur more often in females
a. True
b. False
Answer: A. Hypohidrosis was reported by 53% of males and 28% females. Hyperhidrosis occur more often in females than males p. 2297
Agalsidase beta (Genzyme) is administered a. 1mg/kg twice a week
b. 0.2 mg/kg twice a week
c. 1mg/kg twice a day
d. 0.2 mg/kg twice a day
Answer:
A. 1mg/kg biweekly – agalsidase beta p. 2303
B. 0.2mg/kg biweekly – agalsidase alpha
most prevalent lysosomal storage disorder
- Gaucher disease
- Fabry disease
what do you call the characteristic, electron-dense, lamellated, intracytoplasmic vacuolar inclusions typically seen on electron microscopy of patients with fabry disease?
Zebra bodies
They exhibit a pattern of alternating light and dark 4- to 6-nm bands. These inclusions may be present in biopsies of angiokeratoma or from normal skin.
classical feature of Fabry disease and thought largely to be a consequence of autonomic neuropathy, although substrate accumulation within sweat glands may play a role
Reduced sweating
frequent complaint among Fabry patients
“Cold intolerance” and the development of pain in the extremities in cold environments
most common ocular finding in Fabry disease
cornea verticillata (opacities in the cornea characterized by 1 or more lines radiating from near the center of the cornea)
constant feature and increasingly recognized as the major cause of death in both male and female patients with Fabry disease
Cardiac manifestations
A common presentation is with** left ventricular hypertrophy,** but mitral valve prolapse, arrhythmia, and coronary artery disease can all be present
most disturbing and early symptom of Fabry disease
Pain
Two formulations of ERT
give the doses
- agalsidase beta (Genzyme) - 1 mg/kg biweekly
- agalsidase alpha (Replagal) - 0.2 mg/kg biweekly
recommended for all symptomatic males and at the first sign of organ dysfunction in females
ENZYME REPLACEMENT THERAPY
Chaperone-based enzyme enhancement therapy approved by the regulatory authorities in both the United States and Europe.
It consists of small molecules that rescue misfolded/ mistrafficked enzymes from the lysosomes and transport them to the endoplasmic reticulum
Migalastat
