Foot Process Effacement with Normal Urinalysis in Classic Fabry Disease

Abstract

Fabry disease is an X-linked glycosphingolipidosis caused by deficient synthesis of the enzyme α-galactosidase A, which results in glycosphingolipidosis, predominantly globotriaosylceramide, progressively accumulating in systemic tissue. A dominant complication of Fabry disease is nephropathy. The average age for the development of clinical nephropathy is 27 years in male patients, with up to half of all patients developing end-stage renal failure by their 50s. A recent study revealed podocytes play important roles in antiproteinuria. Podocyte injury leads to foot process effacement and proteinuria. The foot process effacement induces podocyte depletion from the glomerular wall, glomerulosclerosis, and results in end-stage renal failure. We report on a 13-year-old boy with classic Fabry disease, who developed foot process effacement and podocyte depletion even before proteinuria appeared. At the time, his only symptom of Fabry disease was acroparesthesia. He was administered Agalsidase β (1 mg/kg/dose div) every other week and 14 months after treatment, his renal function remained normal. This is the first report of a patient with classic Fabry disease, with only acroparesthesia, who had normal urinalysis but manifested foot process effacement and podocyte depletion. Podocytes are highly differentiated cells with a limited capacity for cell division and replacement. The large individual variation and often progressive nature of this disease raises concerns about the appropriate timing for initiating enzyme replacement therapy (ERT). Recent data have shown a limited effect of ERT on progressive organ damage. In our case, ERT was initiated before proteinuria appeared, with good outcome.

Appendices

Synopsis

Normal urinalysis does not always indicate normal kidney tissue in Fabry disease.

Details of the Contributions of Individual Authors

Dr. Kanai, the author of this article and the doctor of this patient; Prof Yamagata and Prof Momoi, advisors for this article; Dr. Ito, Dr. Odaka, Dr. Saito, and Dr. Aoyagi, assisted in treating this patient and writing this article; Dr. Kobayashi and Prof Ohashi, detected the gene abnormality; and Prof Ueda, reported the pathologic findings.

Name of One Author Who Serves as Guarantor for This Article

Dr. Takahiro Kanai.

A Competing Interest Statement

We declare that the answers to all questions on the JIMD competing interest form are NO; therefore, we have nothing to declare.

Details of Funding

We confirm independence from the sponsors; the content of the article has not been influenced by the sponsors.

Details of Ethics Approval for This Study

This study was approved by The Ethics Committee of Jichi Medical University with the patient consent statement.