Progressive renal failure is a major complication of Fabry disease (FD). Heterogeneity of FD phenotype has hampered establishment of a consensus guideline for the need and dose adjustment for enzyme replacement therapy (ERT). This is while both age of ERT initiation and ERT dosage can affect its efficacy [1, 2]. Thus, late ERT initiation when patients have >1 g/d proteinuria cannot prevent progressive glomerular filtration rate (GFR) decline and lower ERT doses are less efficacious in clearing podocytes (PC), an essential cell in FN progression, from globotriaocylceramide (GL3) [2]. Therefore, there is a strong need for a biomarker to detect early FD nephropathy (FN) and stratify patient based on FN risk to guide treatment initiation and dose adjustment. Currently, proteinuria and microalbuminuria are used for this purpose [3, 4], but, these are not sensitive to detect early FN lesions [3, 5, 6] and are much less precise renal disease predictors in females with FD [7]. Biopsy studies suggest PC injury occurs early and is progressive with increasing age in young FD patients [5]. Thus, markers of PC injury are promising candidates to detect early FN. PC have limited capacity to regenerate [8]. PC injury and loss leads to segmental and global glomerulosclerosis [9, 10], common and irreversible lesions in late stages of FN. Injured PC fall into the urine. Quantification of urine PC (podocyturia [PCU]) is robust evidence of PC injury with diagnostic and prognostic values in other kidney diseases [11-13]. It is likely that PCU in FD precedes and leads to proteinuria, glomerulosclerosis and reduced GFR. If true, PCU may be useful to predict FN risk and guide FD treatment. Preliminary data show that urine apoptotic PC per creatinine (hereafter used interchangeably with PCU for simplicity) correlates with age, urinary albumin (UACR) and protein creatinine ratios (UPCR) in adult FD patients. However, we have no information about PCU in young FD patients, where a non-invasive and sensitive biomarker of FN is most needed to guide treatments.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZTR1-CI-8 (01))
Program Officer
Morris, Jill A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Minnesota Twin Cities
United States
Zip Code
Ou, Li; Przybilla, Michael J; Whitley, Chester B (2018) Metabolomics profiling reveals profound metabolic impairments in mice and patients with Sandhoff disease. Mol Genet Metab :
McIntosh, Paul T; Hobson-Webb, Lisa D; Kazi, Zoheb B et al. (2018) Neuroimaging findings in infantile Pompe patients treated with enzyme replacement therapy. Mol Genet Metab 123:85-91
Nestrasil, Igor; Ahmed, Alia; Utz, Josephine M et al. (2018) Distinct progression patterns of brain disease in infantile and juvenile gangliosidoses: Volumetric quantitative MRI study. Mol Genet Metab 123:97-104
Ou, Li; Przybilla, Michael J; Koniar, Brenda et al. (2018) RTB lectin-mediated delivery of lysosomal ?-l-iduronidase mitigates disease manifestations systemically including the central nervous system. Mol Genet Metab 123:105-111
Desai, Ankit K; Walters, Crista K; Cope, Heidi L et al. (2018) Enzyme replacement therapy with alglucosidase alfa in Pompe disease: Clinical experience with rate escalation. Mol Genet Metab 123:92-96
Sindelar, Miriam; Dyke, Jonathan P; Deeb, Ruba S et al. (2018) Untargeted Metabolite Profiling of Cerebrospinal Fluid Uncovers Biomarkers for Severity of Late Infantile Neuronal Ceroid Lipofuscinosis (CLN2, Batten Disease). Sci Rep 8:15229
Shapiro, Elsa G; Whitley, Chester B; Eisengart, Julie B (2018) Beneath the floor: re-analysis of neurodevelopmental outcomes in untreated Hurler syndrome. Orphanet J Rare Dis 13:76
Ou, L; Przybilla, M J; Whitley, C B (2018) SAAMP 2.0: An algorithm to predict genotype-phenotype correlation of lysosomal storage diseases. Clin Genet 93:1008-1014
Eisengart, Julie B; Rudser, Kyle D; Xue, Yong et al. (2018) Long-term outcomes of systemic therapies for Hurler syndrome: an international multicenter comparison. Genet Med 20:1423-1429
Kazi, Zoheb B; Desai, Ankit K; Troxler, R Bradley et al. (2018) An immune tolerance approach using transient low-dose methotrexate in the ERT-naïve setting of patients treated with a therapeutic protein: experience in infantile-onset Pompe disease. Genet Med :

Showing the most recent 10 out of 118 publications