Fabry disease is a rare genetic disorder caused by a deficiency of the enzyme alpha-galactosidase A. This enzyme deficiency leads to the buildup of a fatty substance called globotriaosylceramide (Gb3 or GL-3) in various cells throughout the body. Over time, this accumulation causes damage to multiple organs and systems, resulting in a wide range of complications that can severely affect quality of life and longevity.
One of the most significant complications of Fabry disease involves the **kidneys**. The buildup of Gb3 in kidney cells leads to progressive kidney damage, which often starts with proteinuria (excess protein in the urine) and gradually advances to chronic kidney disease. If untreated, this can progress to end-stage renal failure, requiring dialysis or kidney transplantation. Kidney involvement is a major cause of morbidity and mortality in Fabry patients.
The **heart** is another critical organ affected by Fabry disease. Fatty deposits accumulate in the heart muscle, causing a condition known as **cardiomyopathy**. This typically manifests as thickening of the heart walls (hypertrophic cardiomyopathy), which impairs the heart’s ability to pump blood efficiently. Patients may experience symptoms such as shortness of breath, chest pain, palpitations, and fainting. Over time, this can lead to heart failure, arrhythmias (irregular heartbeats), and an increased risk of sudden cardiac death. The heart complications are often a leading cause of death in Fabry disease.
Neurological complications are also common and can be quite debilitating. Many patients suffer from **neuropathic pain**, often described as burning or tingling sensations in the hands and feet (acroparesthesia). This pain can be severe and chronic. Additionally, Fabry disease can cause damage to small blood vessels in the brain, leading to **stroke** or transient ischemic attacks (mini-strokes), sometimes at a young age. Other neurological symptoms include dizziness, hearing loss, and problems with sweating (hypohidrosis), which can affect temperature regulation.
The skin is frequently affected, with many patients developing small, dark red or purple spots called **angiokeratomas**, typically found between the belly button and knees. These spots are caused by the buildup of Gb3 in the skin’s blood vessels and are a visible sign of the disease.
Fabry disease can also affect the **gastrointestinal system**, causing symptoms such as abdominal pain, diarrhea, nausea, and vomiting. These symptoms result from the involvement of the autonomic nervous system and blood vessels supplying the digestive tract.
Eye complications include **corneal verticillata**, a distinctive whorl-like pattern on the cornea that does not usually affect vision but can be detected during an eye exam and helps in diagnosis.
Other less common but serious complications include hearing loss, tinnitus (ringing in the ears), and involvement of the lungs, which may cause breathing difficulties.
Because Fabry disease affects multiple organs, complications often overlap and worsen over time if untreated. The disease can significantly reduce life expectancy, especially in males, due to kidney failure, heart disease, and stroke.
Managing Fabry disease involves enzyme replacement therapy or pharmacologic chaperones to reduce Gb3 buildup, but complications such as kidney failure, heart problems, and strokes often require additional specific treatments and careful monitoring.
In summary, the complications of Fabry disease are extensive and affect many body systems, including the kidneys, heart, nervous system, skin, gastrointestinal tract, and eyes. These complications can cause chronic pain, organ failure, and life-threatening events, making early diagnosis and comprehensive management crucial.
