Beyond predicting diagnosis: Is there a role for measuring biotinidase activity in liver glycogen storage diseases?

Areeg El-Gharbawy; Adviye A Tolun; Carine A Halaby; Stephanie L Austin; Priya S Kishnani; Deeksha S Bali

doi:10.1016/j.ymgmr.2022.100856

Beyond predicting diagnosis: Is there a role for measuring biotinidase activity in liver glycogen storage diseases?

Mol Genet Metab Rep. 2022 Feb 28:31:100856. doi: 10.1016/j.ymgmr.2022.100856. eCollection 2022 Jun.

Authors

Areeg El-Gharbawy¹, Adviye A Tolun^{2

3}, Carine A Halaby¹, Stephanie L Austin¹, Priya S Kishnani¹, Deeksha S Bali^{1

4}

Affiliations

¹ Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
² NSW Biochemical Genetics Service, The Children's Hospital at Westmead, Westmead, NSW, Australia.
³ Disciplines of Genomic Medicine, and Child and Adolescent Health, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
⁴ Biochemical Genetics Laboratory, Duke University Health System, Durham, NC, USA.

Abstract

Introduction: Biotinidase synthesis is needed to recycle biotin for essential metabolic reactions. Biotinidase activity is lower than normal levels in advanced liver disease but is higher in hepatic glycogen storage disorders (GSDs), however the cause of this association remains unclear.

Methods: In this study, biotinidase activity was measured in plasma samples from 45 individuals with hepatic GSDs; GSDI (a, b; n = 25) and GSD III (a, b; n = 20), complemented by a chart review to associate biotinidase activity levels with clinical laboratory and imaging findings known to be implicated in these GSDs.

Results: Our findings showed variation in biotinidase activity levels among subjects with GSD I and III; biotinidase activity correlated positively with hypertriglyceridemia in subjects with GSD I (r = 0.47, P = 0.036) and GSD III (r = 0.58, P = 0.014), and correlated negatively with age (r = -0.50, P = 0.03) in patients with GSD III. Additionally, biotinidase activity was reduced, albeit within the normal range in subjects with evidence of fibrosis/cirrhosis, as compared to subjects with hepatomegaly with or without steatosis (P = 0.002).

Discussions: These findings suggest that abnormal lipid metabolism in GSD I and III and progressive liver disease in GSD III may influence biotinidase activity levels. We suggest that a prospective, multi-center, longitudinal study designed to assess the significance of monitoring biotinidase activity in a larger cohort with hepatic GSDs is warranted to confirm this observation.

Take-home message: Altered lipid metabolism and advancing liver fibrosis/cirrhosis may influence biotinidase activity levels in patients with hepatic glycogen storage disease. Thus, longitudinal monitoring of biotinidase activity, when combined with clinical and other biochemical findings may be informative.

Keywords: Biomarker; Biotinidase; GSD type I; GSD type III; Hepatic glycogen storage disease; Long-term disease monitoring.