Fabry Disease causes in adults
Fabry disease is a rare, inherited disorder that results from the deficiency of an enzyme called alpha-galactosidase A. This enzyme deficiency leads to the accumulation of a specific type of fat, called globotriaosylceramide (Gb3 or GL-3), within various tissues and organs throughout the body. While Fabry disease is often diagnosed in childhood or adolescence, it can also manifest in adults, sometimes with subtle symptoms that are easily overlooked or misattributed to other common conditions.
In adults, Fabry disease causes primarily stem from its progressive nature. Over time, the buildup of Gb3 damages small blood vessels and nerve endings, leading to a wide range of symptoms. Cardiovascular issues are among the most serious consequences, with many adults experiencing hypertrophic cardiomyopathy, arrhythmias, or hypertension as a result of the disease’s impact on the heart and blood vessels. These issues can lead to heart failure or an increased risk of stroke if not properly managed.
Renal complications are also common in adult Fabry patients. The accumulation of Gb3 in kidney cells can cause proteinuria, decreased kidney function, and eventually lead to chronic kidney disease or renal failure. Regular monitoring of kidney function is crucial for early detection and intervention, which can slow disease progression.
Neurological symptoms in adults often include peripheral neuropathy, characterized by burning pain, tingling, or numbness, especially in the hands and feet. This is due to the nerve damage caused by Gb3 deposits. Additionally, some adults experience cerebrovascular events such as strokes or transient ischemic attacks, which may occur suddenly and without warning, owing to the involvement of cerebral blood vessels.
Other manifestations of Fabry disease in adults include skin lesions called angiokeratomas—small, dark red or black spots that often appear on the lower trunk and groin—and decreased sweating, which can impact thermoregulation. Hearing loss and gastrointestinal issues like abdominal pain, diarrhea, or nausea are also reported.
The causes of Fabry disease in adults are primarily rooted in genetics. It is an X-linked disorder, meaning the defective gene responsible for producing alpha-galactosidase A is located on the X chromosome. Men, having only one X chromosome, are more frequently and severely affected, while women, with two X chromosomes, may have milder symptoms or remain asymptomatic due to random X-inactivation. However, some women can also develop significant symptoms, especially if their X chromosome carrying the normal gene is inactivated in certain tissues.
The mutation of the GLA gene, which encodes the alpha-galactosidase A enzyme, is the root cause. Over 900 different mutations have been identified, and the severity of symptoms often correlates with the specific mutation present. Some mutations result in no enzyme activity at all, leading to classic Fabry disease, while others produce residual enzyme activity, often associated with later-onset, milder forms of the disease.
Diagnosis in adults involves enzyme activity testing and genetic analysis. Early diagnosis is vital because targeted treatments such as enzyme replacement therapy (ERT) or chaperone therapy can help reduce Gb3 accumulation, alleviate symptoms, and prevent severe long-term complications. Due to the insidious onset and diverse presentation, a high index of suspicion is necessary, especially in patients with unexplained cardiac, renal, or neurological symptoms.
In conclusion, Fabry disease causes in adults are primarily due to genetic mutations leading to enzyme deficiency and subsequent lipid accumulation. Its manifestations span multiple organ systems, emphasizing the importance of awareness, early diagnosis, and comprehensive management to improve quality of life and outcomes.
