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Clinical features and enzyme replacement therapy in 10 children with Fabry disease
Qian Li1,2, Jing Wang1,2, Minle Tian3
1Department of Pediatric Nephrology and Rheumatism and Immunology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Insights
This study highlights the diverse clinical features of Fabry disease (FD) in children, emphasizing the importance of early diagnosis through genetic testing and family screening for effective enzyme replacement therapy (ERT). Early intervention with ERT, such as agalsidase alpha and beta, shows promise with minimal adverse effects.
Area of Science:
- Pediatrics
- Genetics
- Metabolic Disorders
Background:
- Fabry disease (FD) is a rare genetic lysosomal storage disorder.
- It results from mutations in the GLA gene, leading to alpha-galactosidase A deficiency.
- Accumulation of globotriaosylceramide (Gb3) and its analogues causes multi-systemic manifestations.
Purpose of the Study:
- To summarize the clinical features, diagnostic approaches, and outcomes of enzyme replacement therapy (ERT) for Fabry disease in pediatric patients.
- To analyze the genetic variations and treatment responses in a cohort of children diagnosed with FD.
Main Methods:
- Retrospective analysis of clinical data, laboratory tests, genetic variations, and treatment of 10 children with Fabry disease.
- Diagnosis was confirmed through genetic testing, enzyme activity assays, and biomarker analysis.
- Patients received enzyme replacement therapy with agalsidase alpha or beta.
Main Results:
- Seven of the 10 pediatric patients were symptomatic, presenting with acral neuralgia, hypo-hidrosis, and cutaneous angiokeratoma.
- Other manifestations included corneal opacity, renal impairment, cardiac abnormalities, and hearing loss.
- A novel GLA gene mutation, c.1059_1061delGAT (p.met353del), was identified.
- ERT led to a significant decrease in Lyso-GL-3 levels in most patients, with agalsidase beta showing good short-term tolerance.
Conclusions:
- Childhood Fabry disease presents with varied clinical manifestations, necessitating comprehensive diagnostic evaluation including family history, enzyme assays, biomarkers, and genetic testing.
- Pedigree and high-risk population screening are crucial for early detection and timely treatment.
- Short-term ERT with agalsidase alpha and beta demonstrated a favorable safety profile in this pediatric cohort.
Objective:
To summarize the clinical features, diagnosis and enzyme replacement therapy(ERT) of Fabry disease (FD) in children.
Methods:
The clinical data, laboratory tests, genetic variations and treatment of 10 FD children diagnosed in Shandong Provincial Hospital from September 2020 to June 2022 were retrospectively analyzed.
Results:
Among the 10 cases from 6 families, 7 patients were boys of 4 to 13 years of age, and 3 were girls of 12 to 15 years of age. There were 7 symptomatic patients, including 6 boys and 1 girl. All 7 patients presented with acral neuralgia. Five patients had little or no sweating. Five patients presented with cutaneous angiokeratoma. Two patients had abdominal pain. One patient developed joint symptoms. Four patients had corneal opacity. One patient had hearing loss; one patient had short stature. One patient had mild proteinuria and 1 patient had dysplasia of the right kidney with decreased eGFR (55.28 ml/min.1.73 m2). The left ventricular mass index was slightly elevated in 1 patient. Three patients had mild obstructive ventilatory dysfunction; a small amount of effusion in the intestinal space of the lower abdomen or mild fatty liver was found in 2 patients. Partial empty sella turcica in 1 patient. A total of 6 GLA gene variants were detected in 10 children, among which C.1059_1061delGAT (p.met353del) was a newly discovered mutation. Five children received ERT, of which 4 were treated with agalsidase beta and 1 was treated with agalsidase alpha. Only 1 patient had anaphylaxis. Lyso-GL-3 levels decreased significantly in the first 3 months of ERT initiation and remained relatively stable thereafter in 3 patients. The Lyso-GL-3 level was decreased, but renal impairment continued to progress in 1 patient treated with agalsidase alpha.
Conclusion:
The clinical manifestations of FD in childhood are diverse, and it is necessary to make a definite diagnosis by combining family history, enzyme activity, biomarkers, gene testing and other indicators. Pedigree screening and high-risk population screening are helpful for early identification, early diagnosis and early treatment. No serious adverse reactions were found during the short-term treatment with agalsidase alpha and beta.
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