Markedly Elevated Chitotriosidase Activity and Enhanced Autophagy in Neonatal Andersen Disease (Glycogen Storage Disease Type IV)
Background: The differential diagnosis of marked neonatal hypotonia is broad. Chitotriosidase is a human chitinase secreted by activated macrophages. Since elevated plasma values are found in a variety of lysosomal storage disorders (LSD), this parameter can be used to screen for an underlying LSD.
Methods: We report on a newborn with profound muscular hypotonia and paucity of movements, necessitating artificial ventilation immediately after birth.
Results: An extensive metabolic work-up revealed β-ureidopropionase deficiency not explaining the patient’s clinical symptoms, and markedly elevated chitotriosidase activities (6,088 nmol/h/mL, normal < 190), although the girl displayed no signs of a LSD. A muscle biopsy performed at age 4 weeks showed a severe myopathy with abundant polyglucosan bodies, suggesting a neonatal form of glycogen storage disease type IV (GSD IV), which was confirmed by measuring highly reduced glycogen debranching enzyme activities in different tissues. Muscle biopsy analysis using ultrastructural and immunohistochemical methods performed to elucidate why chitotriosidase is increased in GSD IV, displayed numerous endomysial macrophages enhanced lysosomal activity, and activated autophagy.
Conclusion: These findings show that the simple determination of chitotriosidase activity may substantially narrow the differential diagnosis of neonatal hypotonia, add GSD type IV to the list of disorders associated with markedly elevated chitotriosidase activities, and append this disorder to the listing of neuromuscular diseases with enhanced autophagy.