Cascade genetic screening for diagnostics of preclinical forms of Fabry disease in children

The article is devoted to Fabry disease, which is a very rare disorder (orphan disease). Fabry disease is a multisystem enzymopathy, the second most common lysosomal disorder after Gaucher disease. Fabry disease is related to the lysosomal storage of the decomposition product of complex lipids, such as globotriaosylceramide (GL-3 and lyso GL-3) in the endothelial cells of the heart vessels, kidneys, brain and peripheral nervous system resulting ftom a decrease in the activity of alpha-galactosidase-A enzyme (α -GAL A). The example of a family case in the article reflects the necessary diagnostic algorithm for early verification of this disease. It is important to evaluate organs – systems, the control of the plasma globotriaosylsphingosine (Plasma Gb3) biomarker for the timely initiation of etiopathogenetic enzyme replacement therapy, which should
be used in children with neuropathic pain and albuminuria (with a creatinine level in blood plasma > 3 mg/mmol), severe gastrointestinal tract lesions, abdominal pain and heart damage.
Еnzyme replacement therapy should also be used for the asymptomatic form of Fabry disease in boys from the age of 7. The article demonstrates the correlation of the therapy and prognosis of patients with etiotropic enzyme replacement therapy prescription.
Cascade genetic screening of children having at least one first-degree relative with Fabry disease is the simplest and most effective method for diagnosing the disease. It has been shown that Fabry disease is a rare disorder and a high index of professional medical competence is required for the initial diagnosis. Early detection of Fabry disease in clinical practice may be difficult due to the heterogeneity of the clinical manifestations of the disease and the similarity with other rheumatological diseases that are more common in children. Neuropathic pains in the extremities, acroparesthesia in combination with abdominal pain and connective tissue dysplasia in boys can serve as “Red Flags” for doctors, allowing to suspect Fabry disease. All children with Fabry disease, including those with preclinical forms of the disease, need constant control and regular clinical monitoring. The article demonstrates an examination of 24 members of one family, 12 of which with Fabry disease, and thus verifies the algorithm for diagnosing this disease.