Overview of Fabry Disease symptoms
Fabry disease is a rare genetic disorder that results from a deficiency of the enzyme alpha-galactosidase A. This enzyme deficiency causes the buildup of a fatty substance called globotriaosylceramide (Gb3 or GL-3) within various cells of the body, leading to a wide range of symptoms affecting multiple organs. Because of its diverse presentation, early recognition and diagnosis are crucial for management and improving quality of life.
The symptoms of Fabry disease often begin in childhood or adolescence but may not become apparent until later in adulthood. One of the earliest and most characteristic signs is pain, particularly burning or tingling sensations in the hands and feet, a condition known as acroparesthesia. This neuropathic pain can be episodic or persistent and often worsens with exercise, heat, or fatigue. Along with pain, individuals may experience decreased sweating (hypohidrosis or anhidrosis), which can make it difficult to regulate body temperature and increase susceptibility to heat intolerance.
Gastrointestinal issues are also common, including episodes of abdominal pain, diarrhea, and nausea, which can be attributed to Gb3 accumulation in the gastrointestinal tract. Some individuals may experience difficulty with digestion or a feeling of fullness after eating small amounts. These symptoms can be mistaken for other gastrointestinal disorders, leading to delays in diagnosis.
Cutaneous manifestations are another hallmark of Fabry disease. The appearance of small, reddish-purple skin lesions called angiokeratomas, primarily located in the bathing suit area, groin, or around the navel, is distinctive. These lesions result from dilated blood vessels and are often visible upon examination. Additionally, some patients develop a characteristic corneal opacity called cornea verticillata, which can be detected through slit-lamp examination, although it usually does not affect vision.
As Fabry disease progresses, it can cause significant damage to the kidneys, heart, and brain. Kidney involvement may manifest as proteinuria, decreased kidney function, or eventual renal failure. Cardiac symptoms often include arrhythmias, hypertrophic cardiomyopathy, or chest pain due to myocardial involvement. Cerebrovascular complications, such as strokes or transient ischemic attacks, can also occur, especially in untreated individuals.
The progression of symptoms varies widely among patients, depending on the severity of enzyme deficiency and the age at onset. Some individuals experience only mild symptoms, while others develop severe complications early in life. While the initial symptoms are often neurological or dermatological, the later stages tend to involve major organ systems, underscoring the importance of early diagnosis and intervention.
In summary, Fabry disease presents with a constellation of symptoms that reflect its systemic nature. Neuropathic pain, skin lesions, gastrointestinal discomfort, and ocular changes are common early signs. As the disease advances, renal, cardiac, and neurological complications can develop, emphasizing the need for awareness among healthcare providers and patients for timely diagnosis and management.
