Clinical Therapeutics/Volume 34, Number 4S, 2012 A number of urinary biomarkers have been proposed to monitor the efcacy

of ERT in Fabry patients. While measurement of Gb-3 is certainly a useful biomarker, for some patients, alterations in urinary concentration does not always appear to reect ERT administration or clinical improvement. Consequently, there is a need for a better biomarker to facilitate patient monitoring. Research in our laboratory is attempting to identify such a urinary biomarker, and initial ndings will be discussed. FURTHER READING
Aerts JM, Groener JE, Kuiper S, et al. Elevated globotriaosylsphingosine is a hallmark of Fabry disease. Proc Natl Acad Sci U S A. 2008;105:28122817. Zarate YA, Hopkin RJ. Fabrys disease. Lancet. 2008;372:14271435.

Kidney Histology
Prof. Agnes B. Fogo Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee In Fabry nephropathy, -galactosidase deciency leads to accumulation of glycosphingolipids in all kidney cell types, proteinuria, and progressive loss of kidney function. Previous studies of renal biopsies have focused on the identication of these deposits for a diagnosis of the disease and their modulation in response to enzyme-replacement therapy (ERT). An international working group of nephrologists from 11 Fabry centers identied adult Fabry patients, and pathologists scored histologic changes on renal biopsies. We aimed to score disease-specic lesions and secondary changes of sclerosis and brosis that might relate to progressive loss of renal function. A standardized scoring system was developed with a modied Delphi technique assessing 59 Fabry nephropathy cases. Each case was scored independently of clinical information by at least 3 pathologists, with an average nal score reported. We assessed 35 males (mean age, 36.4 years) and 24 females (43.9 years) who mostly had clinically mild Fabry nephropathy. The mean serum creatinine was 1.3 mg/dL (114.9 mol/L), estimated glomerular ltration rate was 81.7 mL/min/1.73 m2, and urine protein to creatinine ratio was 1.08 g/g (122.0 mg/mmol). Males had greater podocyte vacuolization on light microscopy (mean score) and glycosphingolipid inclusions on semi-thin sections than females. Males also had signicantly more proximal tubule, peritubular capillary, and vascular intimal inclusions. Arteriolar hyalinosis was similar, but females had signicantly more arterial hyalinosis. Chronic kidney disease stage correlated with arterial and glomerular sclerosis scores. Signicant changes, including segmental and global sclerosis, and interstitial brosis were seen even in patients with stage 12 chronic kidney disease with minimal proteinuria. The development of a standardized scoring system of both disease-specic lesions (ie, lipid deposition related) and general lesions of progression (ie, brosis and sclerosis), showed a spectrum of histologic appearances even in early clinical stage of Fabry nephropathy. These ndings support the role of kidney biopsy in the baseline evaluation of Fabry nephropathy, even with mild clinical disease. The scoring system will be useful for longitudinal assessment of prognosis and responses to therapy for Fabry nephropathy.

Overlooked Signs and Symptoms: Lung

Ale Linhart, Sudheera Magage, Gabriela Dostalove , and Zdenk Susa Charles University, Prague, Czech Republic The classic phenotype of Fabry disease is a multisystemic disorder affecting many organ systems. Although most severe complications include renal, cardiac, and cerebrovascular events, lung disease associated with -galactosidase deciency may signicantly contribute to disease burden. Globotriaosylceramide inclusions are detectable in many lung cells, including pneumocytes, ciliary cells, goblet cells, epithelial cells, and smooth muscle cells of the bronchial tree.1

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