Read more about Pedigree analysis of Fabry disease.
Read more about Symptomatic treatment of Fabry disease.
Read more about Symptomatic treatment of Fabry disease.
The Fabry disease gene is located on the X chromosome, and the condition is transmitted following an X-linked inheritance pattern. When there is a suspicion that a patient may be affected by Fabry disease, a pedigree analysis should be undertaken to inform diagnosis and identify any relatives of the patient who may have symptomatic disease or be carriers.1 Thorough family history evaluation and pedigree analysis can ensure an earlier diagnosis and more effective treatment for undiagnosed or misdiagnosed individuals.
Following a diagnosis of Fabry disease, genetic counselling should be offered to every patient to assist them in assessing their situation, and in deciding if and how to discuss the diagnosis with their family. Denial and lack of communication with the family are frequently observed, especially in cases of severe disease manifestations. Family tensions are often exposed following a diagnosis.
Fabry disease is an incurable condition and patients have to take treatment life-long, irrespective of whether it is treating the signs and symptoms of disease or managing the underlying metabolic defect. Broadly speaking, there are currently two complementary approaches to the management of Fabry disease:
ERT is the standard treatment for Fabry disease. ERT was introduced in 2001 and offered the first opportunity to treat the underlying enzyme deficiency.1,2 Considered the standard treatment for Fabry disease, ERT provides an exogenous source of α-galactosidase (α-Gal) A, replacing the deficient enzyme in the body’s cells, 1–4 thus helping to slow disease progression. ERT for Fabry disease is administered intravenously once every other week and is indicated for patients with a confirmed diagnosis of Fabry disease.1,2
Some α-Gal A gene mutations (termed ‘amenable mutations’) can lead to misfolded α-Gal A variants that have residual enzyme activity but are unstable. This results in impaired delivery of the enzyme into lysosomes and misassembled or aggregated enzyme in the endoplasmic reticulum, leading to a loss of or reduction in enzyme function.1,2 These variants may be stabilised by chemical chaperones, which bind to the enzyme’s active site to promote correct folding and trafficking of endogenous α-Gal A.3 Chaperone therapy is administered orally and is only feasible and approved for patients with an amenable mutation.4