However, confirmation of the disease-causing GLA mutation is important to help establish the disease phenotype. α-Gal A activity testing is diagnostic for male patients. α-Gal A and lyso-GL-3 analysis and GLA sequencing in DBS for the diagnosis of FD were evaluated. Testing from dried blood spots (DBSs) is now possible for LSDs, making population screening technically feasible. Considering the diversity and “nonspecific” clinical manifestations accompanying with life-threatening aspects of FD, methods to improve effective screening and management of suspect cases are needed. On average, this process comes 14–16 years following the onset of the first symptoms. A typical patient’s odyssey means multiple visits to more than ten different medical specialists before the child achieves a confirmatory diagnosis of FD. A comprehensive care plan should be implemented to guide the management of children with FD.Īlthough FD has been known for more than a century, this LSD remains poorly recognized, especially in children in China. Asymptomatic children with GLA mutations should be followed closely for the development of signs, symptoms, or laboratory changes, which would warrant treatment initiation. Early treatment before the onset of potentially irreversible vital organ pathology is ideal. Enzyme replacement therapy (ERT) and adjunctive treatments can provide significant clinical benefit. Ĭurrently, numerous GLA mutations are reported in gene mutation databases. Newborn screening identified a surprisingly high frequency of males with FD (~ 1 in 1,250). Other manifestations of FD, such as renal and cardiac disease, manifest later in adolescence or adulthood. Young patients may initially experience pain, hypohidrosis and gastrointestinal symptoms. Phenotypes vary from the “classic” phenotype, with pediatric onset and multiorgan involvement, to “nonclassical” later onset, a predominantly cardiac phenotype. This enzyme deficiency results in an accumulation of globotriaosylceramide (GL-3) and globotriaosylsphingosine (deacylated form of GL-3, lyso-GL-3). We should pay more attention to the high-risk profiles of pain, angiokeratoma, decreased sweating, and unexplained chronic kidney disease in children.įabry disease (OMIM 301,500, FD) is an X-linked lysosomal storage disorder (LSD) caused by mutations in the GLA gene leading to deficient α-galactosidase A (α-Gal A) activity. Screening and management of children with FD is effective based on a defined screening protocol and a multidisciplinary approach.
Four of them started to receive enzyme replacement therapy. Family screening of these 10 diagnosed children indicated that 9 boys inherited it from their mothers and 1 girl inherited it from her father. Furthermore, another 3 children diagnosed with FD were referred from other hospitals. Two neonates were detected early with GLA mutations in the hospital, with a yield of detection of 0.14% (2/1420). These 5 diagnosed children were referred due to a high-risk profile of pain accompanied by dermatological angiokeratoma and hypohidrosis (n = 2), pain accompanied by abnormal liver function (n = 1), pain only (n = 1), and unexplained renal tubular dysfunction (n = 1). However, twelve months following the MDT program's implementation, thirty-five children with high-risk profiles were referred for screening by DBS triple-test, with a yield of diagnosis of 14.3% (5/35). Resultsīefore the establishment of the MDT, no case was diagnosed with FD in the hospital. Evaluation, family screening, and genetic counselling were implemented after screening by the MDT management team. For newborns who were undergoing genetic testing in the hospital, the GLA gene was listed as a routine analysis gene. Children with high-risk characteristics were referred by the MDT screening team using the dried blood spot (DBS) triple-test (α-galactosidase A, globotriaosylsphingosine, GLA gene). MethodsĪ multidisciplinary team (MDT) of pediatric FD experts was launched at Children’s Hospital of Fudan University. This study aims to explore how it can be done effectively from a multidisciplinary perspective for children with FD at a tertiary children’s hospital in China. Considering the diversity and nonspecific clinical manifestations accompanying with life-threatening aspect of this disease, methods to improve effective screening and management of the suspects are needed. Fabry disease (FD) remains poorly recognized, especially in children in China.
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