Fabry disease is a rare, inherited metabolic disorder caused by a deficiency of the enzyme alpha-galactosidase A. This enzyme is responsible for breaking down a specific type of fat called globotriaosylceramide within the body's cells. Due to the lack of this enzyme, globotriaosylceramide accumulates in various tissues and organs, leading to a wide range of symptoms and complications that can affect many different parts of the body.
Fabry disease is caused by alterations or mutations in the GLA gene, which provides instructions for making the alpha-galactosidase A enzyme. Changes in this gene disrupt the structure and function of the enzyme, preventing it from properly breaking down globotriaosylceramide. As a result, this substance accumulates in cells, especially in the skin, kidneys, heart, and nervous system, leading to the various symptoms and complications associated with Fabry disease.
Fabry disease is inherited in an X-linked pattern. In males, a single altered copy of the GLA gene in each cell is enough to cause the condition, as they only have one X chromosome. Females, on the other hand, have two copies of the X chromosome. If a female inherits one altered copy and one normal copy of the GLA gene, she can be a carrier of the condition but may not necessarily develop the full-blown symptoms. The severity of the disease in females can vary widely, depending on factors such as the specific mutation and the pattern of X chromosome inactivation.
Diagnosing Fabry disease involves a comprehensive evaluation that takes into account the patient's clinical features, biochemical analysis, and genetic testing. Healthcare providers may suspect Fabry disease based on the presence of characteristic symptoms, such as episodes of pain, skin lesions, eye abnormalities, and signs of organ damage. Enzyme activity tests can be used to measure the levels of alpha-galactosidase A, which are typically reduced in individuals with Fabry disease. Genetic testing, which can identify specific variants in the GLA gene, is often the definitive way to confirm the diagnosis.
Due to the complexity of its genetics as well as the overlapping spectrum of its symptoms with the clinical manifestations of other diseases, diagnoses of FD still poses as a challenge. In order to confirm FD, a multidisciplinary approach based on data from clinical findings, genetic analysis, and biochemical investigations are essential. LysoGb3 (globotriaosylsphingosine), a deacylated form of Gb3, has been identified to be a useful biomarker in the confirmation of FD diagnosis. It was found to be effective even in symptmatic females with normal or borderline leukocyte enzyme activity as an effect of X-chromosome inactivation.
Although there is no cure for Fabry disease at the moment, various treatments are available to manage the symptoms and delay the progression of the condition. One of the primary treatments is enzyme replacement therapy, which involves the administration of synthetic versions of the alpha-galactosidase A enzyme to help break down the accumulating globotriaosylceramide. Additionally, medications may be prescribed to address specific symptoms, such as pain, gastrointestinal issues, and other complications. Monitoring and management of organ damage, such as kidney failure, heart disease, and stroke, are also crucial components of the treatment plan. Supportive care, including lifestyle modifications, physical therapy, and management of associated symptoms, can also help improve the patient's quality of life.