Glomerular and tubular function in glycogen storage disease

Urinary protein and calcium excretion were assessed in 77 patients with the hepatic glycogen storage diseases (GSD): 30 with GSD-I (median age 12.4 years, range 3.2-32.9 years), 25 with GSD-III (median age 10.5 years, range 4.2-31.3 years) and 22 with GSD-IX (median age 11.8 years, range 1.2-35.4 years). Inulin (C-inulin) and para-aminohippuric acid (C-PAH) clearances were also measured in 33 of these patients. Those with GSD-I had significantly greater albumin (F=15.07, P < 0.001), retinol-binding protein (REP) (F=14.66, P<0.001), N-acetyl-beta-D-glucosaminidase (NAG) (F=9.41, P<0.001) and calcium (F=7.41, P=0.001) excretion than those with GSD-III and GSD-IX. GSD-I patients (n=18) also had significantly higher C-inulin (F=5.57, P=0.009), but C-PAH did not differ (F=0.77, NS). Renal function was normal in GSD-UI and GSD-IX patients. In GSD-I, C-inulin (r=-0.51, P=0.03) and NAG excretion (r=-0.40, P=0.03) were inversely correlated with age, whereas albumin excretion was positively correlated with age (r=+0.41, P=0.03). REP and calcium excretion were generally high throughout all age groups. Hyperfiltration in GSD-I is associated with renal tubular proteinuria that occurs before the onset of significant albuminuria. Deficiency of glucose-6-phosphatase within the proximal renal tubule may primarily cause tubular dysfunction, glomerular hyperfiltration being a secondary phenomenon.