Rare Etiology of Renal Failure in a 25-Year-Old Caucasian Man: Fabry Disease With a Novel Mutation of GLA Gene.

Salem Gaballa,Avan Aljaf,Kashyap Patel,Kyaw M Hlaing,Jane Lindsay

doi:10.7759/cureus.9136

Abstract

Fabry disease (FD) is an X-linked recessive lysosomal storage disease caused by a mutation of the galactosidase alpha (GLA) gene, leading to deficiency of α-galactosidase A (alpha-Gal A). This deficiency results in a progressive, multiorgan accumulation of glycolipids, most notably globotriaosylceramide (Gb3), leading to multiorgan failure and subsequently premature death. Gb3 accumulation in the podocytes, epithelial, and mesangial cells of the glomeruli results in progressive renal disease and eventually renal failure and hemodialysis (HD). There are two types of FD: early-onset classical type 1 and late-onset type 2. Although nearly a thousand mutations of the GLA gene have been identified, the majority of them are of unknown significance. Herein we report the case of a 25-year-old Caucasian male with no significant medical history who presented with peripheral neuropathy and end-stage renal failure, requiring HD. He was diagnosed with FD based on the electron microscopy findings of renal biopsy and severely reduced alpha-Gal A activity (<0.4 nmol/mL/hour). A novel mutation of c.281G>T; p.Cys94Phe was identified. On discharge from our facility, he was referred to a renal transplant center and genetic counseling.

Highlights

Fabry disease (FD) is the second most prevalent lysosomal storage disorder after Gaucher disease [1]. It is an X-linked inherited mutation of the galactosidase alpha (GLA) gene of the X chromosome [2]. These mutations result in the absence or deficiency of α-galactosidase A enzyme, which catalyzes the hydrolytic cleavage of the terminal galactose from globotriaosylceramide (Gb3), leading to multiorgan glycosphingolipid accumulations
Random screening has identified less than 1% of hemodialysis (HD) patients as having FD
The diagnosis is established by a low leukocyte alpha-Gal A activity and a variety of mutations in the GLA gene

Summary

Introduction

Fabry disease (FD) is the second most prevalent lysosomal storage disorder after Gaucher disease [1]. A 25-year-old male with no past medical history was brought to the emergency department with complaints of tingling and severe burning sensation in the hands and feet for several days He endorsed associated nausea and non-bilious emesis, poor appetite, and mental fogginess. Due to the patient’s family history of FD, severe neuropathy, and nephrotic range of proteinuria, the genetic testing, alpha-Gal A activity test, and renal biopsy were performed. GAL gene sequencing revealed a novel mutation of c.281G>T; p.Cys94Phe.The patient’s peripheral neuropathy and encephalopathy continued to improve on HD, and his blood pressure improved with hydralazine and amlodipine. He was discharged home with continued outpatient HD, with referral to the renal transplant center along with genetic counseling. ECHO, echocardiogram; TTE, transthoracic echocardiogram; LVH, left ventricular hypertrophy; IVS, interventricular septum

Discussion

Findings

Conclusions

Disclosures