First 2 Fabry Cases with Novel Mutation and Their Associated Clusters in Malaysia
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Published on: August 8, 2022
Andy Sing Ong Tang1, Qi Ying Wong1, Ingrid Pao Lin Ting1
1Department of Internal Medicine, Miri Hospital, Ministry of Health, Miri, Sarawak, Malaysia.
Abstract:
BACKGROUND No cases of Fabry disease (FD) have been reported thus far in Malaysia. We aimed to report the demographic characteristics, clinical manifestations, molecular results, and treatment outcomes of 2 FD cases. This study was a retrospective review of 2 family clusters of FD on follow-up in Sarawak, Malaysia. CASE REPORT Two index patients were confirmed to have FD. Index patient 1, who had nephrotic-range proteinuria and cornea verticillata, carried a variant within exon 4 of the GLA gene: c.610 T>C (p.Trp204Arg). Agalsidase beta (Fabrazyme®) enzyme replacement therapy was initiated, with the absence of neutralizing antibody after 24 months. No hypersensitivity or adverse reactions were reported. The patient's proteinuria and renal function remained stable. Other family members who carried the same mutation were asymptomatic. Index patient 2, who had residual activity of alpha-galactosidase A and a normal globotriaosylsphingosine level, carried a novel GLA mutation of c.548-5T>A. He was diagnosed with end-stage renal disease on regular dialysis and had nonspecific headache with 1 episode of seizure a few years prior to FD genetic screening. One brother had chronic neuropathic pain but refused further investigations. Other family members who had the same mutation were asymptomatic. This mutation has never been reported in literature, and its pathogenicity warrants further studies. CONCLUSIONS It is of utmost importance to increase awareness of FD among clinicians, so that appropriate screening may be done to determine its true prevalence and prompt treatment can be initiated early.
Insights
Two Malaysian Fabry disease (FD) cases highlight the importance of increased clinical awareness for early diagnosis and treatment. This rare genetic disorder requires prompt screening to identify affected individuals and initiate timely management.
Area of Science:
- Genetics
- Rare Diseases
- Biochemistry
Background:
- Fabry disease (FD) is a rare genetic disorder with no previously reported cases in Malaysia.
- This study retrospectively reviewed two family clusters of FD in Sarawak, Malaysia, to characterize demographic, clinical, molecular, and treatment data.
Observation:
- Two index patients were diagnosed with FD. Patient 1 presented with nephrotic-range proteinuria and cornea verticillata, carrying a known GLA gene variant (c.610 T>C).
- Patient 2, with end-stage renal disease and a history of seizures, carried a novel GLA mutation (c.548-5T>A).
- Family members with the same mutations were largely asymptomatic, indicating variable expressivity.
Findings:
- Patient 1 showed stable renal function and proteinuria after 24 months of agalsidase beta enzyme replacement therapy without adverse reactions or neutralizing antibodies.
- The novel GLA mutation in Patient 2 requires further studies to determine pathogenicity.
- One sibling of Patient 2 experienced chronic neuropathic pain, suggesting potential clinical manifestations in other family members.
Implications:
- Increased awareness of Fabry disease among clinicians is crucial for timely diagnosis and intervention in Malaysia.
- Early screening and genetic testing are essential to determine the true prevalence of FD and facilitate prompt treatment.
- Understanding genotype-phenotype correlations, especially for novel mutations, is vital for managing FD effectively.
