Fabrys disease

Fabry's disease, also known as Anderson-Fabry disease, is a rare genetic disorder that affects many parts of the body including the skin, eyes, kidneys, heart, and nervous system. It is categorized under lysosomal storage diseases, which are disorders that result from the malfunction of lysosomal enzymes, leading to the accumulation of harmful substances in cells. Fabry's disease is specifically caused by mutations in the GLA gene, which encodes the enzyme alpha-galactosidase A. This enzyme deficiency leads to the accumulation of globotriaosylceramide (Gb3) within lysosomes, causing progressive damage to cells and tissues throughout the body.

Symptoms

The symptoms of Fabry's disease can vary widely among affected individuals, ranging from mild to severe and may appear in childhood or adulthood. Common symptoms include episodes of pain, particularly in the hands and feet (acroparesthesia); clusters of small, dark red spots on the skin known as angiokeratomas; decreased sweating (hypohidrosis); problems with the gastrointestinal system; cloudiness of the front part of the eye (corneal opacity); and hearing loss. Over time, life-threatening complications such as kidney failure, heart attack, and stroke can develop.

Diagnosis

Diagnosis of Fabry's disease involves a combination of clinical evaluation, family history, and laboratory tests. Enzyme assays can measure the activity of alpha-galactosidase A in the blood, which is significantly reduced in males with the disease. Genetic testing can identify mutations in the GLA gene, confirming the diagnosis and allowing for carrier testing and prenatal diagnosis.

Treatment

While there is no cure for Fabry's disease, treatments are available to manage symptoms and prevent complications. Enzyme replacement therapy (ERT) with recombinant human alpha-galactosidase A is the primary treatment, aiming to replace the deficient enzyme and reduce the accumulation of Gb3. Pain management, kidney dialysis or transplantation, and treatments for heart disease and stroke are also important aspects of care for individuals with Fabry's disease.

Epidemiology

Fabry's disease is a rare condition, affecting approximately 1 in 40,000 to 60,000 males. The disease is less common in females, who are typically carriers of the condition and may have milder symptoms.

Genetics

Fabry's disease is inherited in an X-linked recessive manner, meaning the mutated gene is located on the X chromosome. Males have only one X chromosome and thus one copy of the GLA gene, so they are more severely affected by the disease. Females have two X chromosomes and usually have one normal copy of the GLA gene, which can partially compensate for the defective one, leading to a milder manifestation of the disease.