Fabry disease (FD), also known as Anderson-Fabry disease, is an X-linked recessive X-Linked Recessive Duchenne Muscular Dystrophy lysosomal storage disorder and the 2nd most common of the lysosomal storage disorders (after Gaucher disease Gaucher disease Gaucher Disease (GD) is an autosomal recessive lysosomal storage disorder caused by a deficiency of glucocerebrosidase enzyme activity, resulting in accumulation of glucocerebroside in cells and certain organs. The disease is categorized into 3 types with variable clinical presentation. Gaucher Disease). Fabry disease is caused by a deficiency in the alpha-galactosidase enzyme (alpha-Gal A), resulting in the accumulation of the glycosphingolipid globotriaosylceramide (Gb3) in lysosomes Lysosomes A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured or undergoes membrane fusion. The Cell: Organelles. This accumulation leads to organ dysfunctions and clinical manifestations. Fabry disease is classified into classic (early-onset) and atypical (late-onset) FD. The clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor and severity can vary but may include acroparesthesias, angiokeratomas, stroke, cardiovascular disease, and renal dysfunction. Diagnosis is made by measurement of alpha-Gal A enzyme activity or identification Identification Defense Mechanisms of an alpha-galactosidase A (GLA) gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations. There is no cure for FD. Management is supportive, including pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways control and slowing the progression of disease with enzyme replacement Enzyme replacement Therapeutic replacement or supplementation of defective or missing enzymes to alleviate the effects of enzyme deficiency (e.g., glucosylceramidase replacement for gaucher disease). Severe Combined Immunodeficiency (SCID) or chaperone therapies.
Last updated: 29 Jan, 2022
Histological slide from a kidney biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma in a patient with Fabry disease. The collections of globotriaosylceramide within podocytes are darkly stained.
Image: “Morbus Fabry kidney biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma” by Barisoni L. License: CC BY 2.0 The lysosomal storage pathway:
Fabry disease results from alpha-galactosidase A deficiency, resulting in a build-up of globotriaosylceramide (also known as ceramide trihexoside)
The clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor and severity vary, and men have more severe symptoms than women do.
Musculocutaneous:
Angiokeratoma are often distributed on the buttocks, groin Groin The external junctural region between the lower part of the abdomen and the thigh. Male Genitourinary Examination, umbilicus, and upper thighs. They are occasionally seen on the lips Lips The lips are the soft and movable most external parts of the oral cavity. The blood supply of the lips originates from the external carotid artery, and the innervation is through cranial nerves. Lips and Tongue: Anatomy and oral mucosa Oral mucosa Lining of the oral cavity, including mucosa on the gums; the palate; the lip; the cheek; floor of the mouth; and other structures. The mucosa is generally a nonkeratinized stratified squamous epithelium covering muscle, bone, or glands but can show varying degree of keratinization at specific locations. Stomatitis.
Image: “Angiokeratoma” by Alessandro P Burlina et al AL Amyloidosis. License: CC BY 2.0GI:
Ocular:
Common ocular changes in Fabry disease:
a:
Cornea
Cornea
The transparent anterior portion of the fibrous coat of the eye consisting of five layers: stratified squamous corneal epithelium; bowman membrane; corneal stroma; descemet membrane; and mesenchymal corneal endothelium. It serves as the first refracting medium of the eye.
Eye: Anatomy verticillata
b: Increased vessel tortuosity and aneurysms (arrows)
c: Increased tortuosity of the superior temporal artery and vein
d:
Lens
Lens
A transparent, biconvex structure of the eye, enclosed in a capsule and situated behind the iris and in front of the vitreous humor (vitreous body). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the ciliary body is crucial for ocular accommodation.
Eye: Anatomy
opacity
Opacity
Imaging of the Lungs and Pleura
Renal:
Neurologic:
Cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR):
Auricular:
Other:
Clinical suspicion in children or adolescents will lead to testing and diagnosis. However, a late diagnosis is not uncommon given the varied clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor.