Rare Disease Report

Case of a Patient NOT Having Fabry Disease

NOVEMBER 07, 2013

An interesting case study is being presented at the American Society of Nephrology Kidney Week on Friday. It reports on a man thought to have a rare disease (Fabry disease) but further diagnostic testing revealed he does not. More likely, he has an even rarer disease.  Currently, the diagnosis is not known but it is an interesting study in the trials and tribulations of trying to get properly diagnosed. Below is the abstract being presented at Kidney Week.  


Abstract: [FR-PO1078] What Looks like Fabry Disease, May Not Be Fabry!
Reem Daloul, MD, Francis Dumler, MD, FASN, Ping L. Zhang, MD, PhD, FASN. William Beaumont Hospital, Royal Oak, MI.
Background: Fabry disease is a rare x-linked lysosomal storage disorder caused by deficiency of lysosomal hydrolase alpha-galactosidase A (alpha-Gal A). This results in the accumulation of globotriaosylceramide within the lysosomes of different cell types with eventual organ dysfunction. Renal involvement is characterized by proteinuria and progressive renal failure. Methods/Results: We report a 38 year old previously healthy African American male who presented with intermittent gross hematuria. The patient was otherwise asymptomatic. Family history was strongly positive for chronic kidney disease in both parents, sister, maternal and paternal grandmothers. Urinalysis showed +3 blood, 8 RBCs, 4 WBCs and no protein. Creatinine and eGFR were 1.02 mg/dL and 99 mL/min/1.73m2. Urine protein/creatinine ratio was 0.1. Abdominal CT, renal ultrasound, and cystoscopy were all normal. Renal biopsy showed slight glomerular congestion with occasional foamy cells along the glomerular capillary wall and no proliferation, necrosis, or glomerular sclerosis. CD68 and lysozyme stained sections revealed granular aggregates in the podocytes. Electron microscopy disclosed normal basal membrane thickness without splitting or immune complex deposition and preserved foot processes. Circular and laminated materials were identified in the cytoplasm of the podocytes. These structures correlated with the CD68 positive aggregates identified by light microscopy. The pathological findings are characteristics of Fabry disease. The patient denied any history of neuropathic limb pain, cerebrovascular accidents, heart disease, or skin rash suggestive of telangiectasias or angiokeratomas. Echocardiogram showed normal ventricular wall thickness and valves. Leukocyte Alpha-Gal A was found to be within normal limits.  Conclusions: The sensitivity and specificity of the leukocytes alpha-Gal A assay in males approaches 100%. Normal values in our patient excludes the diagnosis of Fabry disease, particularly in the presence of a negative history and a normal physical examination. It raises the possibility of another rare lysosomal disorder being responsible for this patient's renal involvement. A question that we will turn to genetic testing for further answers.

About Fabry Disease

Fabry disease is an X-linked lysosomal storage disorder that leads to excessive deposition of glycosphingolipids throughout the body. Skin, eye, kidney, heart, brain, and peripheral nervous system are highly vulnerable. Fabry disease is often difficult to diagnose since signs and symptoms are often nonspecific. For example, common symptoms may be fatigue, neuropathy (in particular, burning extremity pain), cerebrovascular effects leading to an increased risk of stroke, tinnitus (ringing in the ears), vertigo, nausea, inability to gain weight, chemical imbalances, diarrhea etc. 

Symptoms do appear in childhood but often go undiagnosed for several years. As the disease progressive, most patients with Fabry disease die in their fourth or fifth decade due to complications arising from renal or cardiovascular problems.

Currently, Genzyme’s Fabrazyme is the only approved treatment for Fabry disease in the United States.  Fabrazyme is also approved in Europe and elsewhere, as is Shire’s Replagal.

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