First 2 Fabry Cases with Novel Mutation and Their Associated Clusters in Malaysia

Case series Patients: Male, 39-year-old (age at diagnosis) • Male, 62-year-old (age at diagnosis) Final Diagnosis: Fabry disease Symptoms: Corneal verticillata • kidney failure • neuropathy • proteinuria Medication: — Clinical Procedure: — Specialty: Genetics • Hematology • Laboratory Diagnostics • Nephrology • Neurology • Ophthalmology OBJECTIVE: Rare disease 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 REPORTS: 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 α-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.