Distinctly Elevated Chitotriosidase Activity in a Child with Congenital Andersen Disease (Glycogen Storage Disease Type IV)

Introduction

The differential diagnosis of marked neonatal hypotonia is broad and includes central and peripheral nervous-system disorders, often necessitating a battery of diagnostic procedures to reach a definite diagnosis. Glycogen storage disease type IV (GSD IV, Andersen disease) is an autosomal recessive disorder in which deficiency of the glycogen-debranching enzyme (GBE) results in storage of an abnormal amylopectin-like glycogen in various tissues. Several clinical variants exist (Bruno C et al., Neurology 2004; 63: 1053–1058). Patients with the very rare congenital form typically present with marked muscular hypotonia at birth, and usually die during early infancy from cardio-respiratory failure (Taratuto AL et al., Neuromuscul Disord 2010; 20: 783–790). PAS-positive, partially diastase resistant polyglucosan bodies (PB) in skeletal muscle are a diagnostic hallmark of the disease (Nolte KW et al., Acta Neuropathol 2008; 116(5): 491–506).

Chitotriosidase is a human chitinase secreted by activated macrophages. Highly elevated plasma values (100–5000 fold) were first described in Gaucher’s disease, while less distinctly increased enzyme activities are detected in various other lysosomal storage disorders (LSD) (Michelakakis H et al., J Inherit Metab Dis 2004; 27: 705-706).

Elevated chitotriosidase activities have also been reported in single patients with GSD IV (Hizarcioglu-Gulsen H et al., JIMD Rep 2014; 17: 63–66). We describe a further child with a congenital form of GSD IV and markedly elevated chitotriosidase levels. A detailed analysis of the patient’s muscle biopsy revealed endomysial macrophage invasion, which may explain the increased chitotriosidase activity, and suggested abnormal autophagy, a phenomenon not yet specifically associated with GSD IV.