Fabry Disease causes in children
Fabry disease is a rare genetic disorder that can affect children, although it is more commonly diagnosed in adults. It belongs to a group of conditions known as lysosomal storage disorders, which result from the deficiency of a specific enzyme. In the case of Fabry disease, the enzyme alpha-galactosidase A is deficient or malfunctioning. This enzyme’s primary role is to break down a fatty substance called globotriaosylceramide (Gb3 or GL-3). When the enzyme activity is impaired, Gb3 accumulates in various tissues and organs, leading to progressive damage.
The causes of Fabry disease in children are rooted in its genetic basis. It is inherited in an X-linked manner, meaning the faulty gene responsible for the disorder is located on the X chromosome. Since males have only one X chromosome, inheriting the defective gene typically results in more severe manifestations of the disease. Females, having two X chromosomes, may have milder symptoms or may be asymptomatic carriers, although some can also experience significant health issues due to random X-chromosome inactivation.
The genetic mutation causing Fabry disease involves alterations in the GLA gene, which encodes the alpha-galactosidase A enzyme. Various mutations, including point mutations, deletions, or insertions, can impair the enzyme’s production or function. These mutations are inherited from a parent who is either affected by the disease or is a carrier. Occasionally, Fabry disease can occur due to spontaneous mutations, though this is quite rare.
In children, Fabry disease can present with a range of symptoms that often develop gradually over time. Early signs may be subtle but can include episodes of pain or burning sensations in the hands and feet—called acroparesthesias—due to nerve involvement. Kidney problems can start early, leading to proteinuria (protein in the urine) or increased blood pressure. Heart issues, such as irregular heartbeat or thickening of the heart walls, may also emerge in childhood or adolescence. Additionally, children might experience skin lesions known as angiokeratomas—small, dark red spots typically found around the lower trunk or groin area.
Beyond physical symptoms, Fabry disease can impact multiple organ systems, leading to a decline in quality of life if not diagnosed and managed early. Since the disease is progressive, early detection is crucial. Diagnosis often involves measuring alpha-galactosidase A enzyme activity, typically through blood or tissue samples, alongside genetic testing to identify mutations in the GLA gene. In males, enzyme activity testing is usually diagnostic, while in females, genetic testing is often necessary, as enzyme levels can sometimes be normal or only mildly decreased.
Understanding the causes of Fabry disease in children emphasizes the importance of early recognition, especially in families with a known history. While there is no current cure, enzyme replacement therapy (ERT) and other treatments can help manage symptoms and prevent serious complications. Ongoing research aims to improve therapies and provide better support for affected children and their families.
In summary, Fabry disease in children results primarily from inherited genetic mutations affecting the GLA gene, leading to enzyme deficiency and subsequent tissue accumulation of harmful substances. Recognizing the genetic and biochemical causes can facilitate early diagnosis, enabling timely intervention to improve health outcomes.
