Congenital disorder of glycosylation caused by mutation of ATP6AP1 gene (c.1036G>A) in a Chinese infant: A case report

Abstract

BACKGROUND

The ATP6AP1 gene coding for the accessory protein Ac45 of the vacuolar-type adenosine triphosphatases (V-ATPase) is located on chromosome Xq28. Defects in certain subunits or accessory subunits of the V-ATPase can lead to congenital disorders of glycosylation (CDG). CDG is a group of metabolic disorders in which defective protein and lipid glycosylation processes affect multiple tissues and organs. Therefore, the clinical presentation of patients with ATP6AP1-CDG varies widely. In this report, we present a case of ATP6AP1-CDG in a Chinese infant, with clinical features and genotype.

CASE SUMMARY

An 8-mo-old boy was admitted to our hospital because unexplained hepatosplenomegaly and elevated transaminases that had been noted while he was being treated for a cough at a local hospital. A post-admission examination at our hospital revealed abnormalities in the infant’s liver, brain, and immune system. Trio-based whole exome gene analysis identified a hemizygous pathogenic mutation c.1036G>A (p.E346K) in exon 9 of the ATP6AP1 gene. This variant of the ATP6AP1 gene has not been reported in East Asian countries until now.

CONCLUSION

Based on the infant’s clinical manifestations and the results of genetic detection, he was clearly diagnosed with ATP6AP1-CDG. The clinical manifestations of children with CDG vary widely. Genetic testing analysis helps in the clinical diagnosis of children with CDG.

Keywords: Congenital disorders of glycosylation; ATP6AP1 mutation; Hepatopathy; Immunodeficiency; Cognitive impairment; Case report

Core Tip: This article reports on an 8-mo-old male infant with hemizygous pathogenic mutation c.1036G>A (p.E346K) in the ATP6AP1 gene. ATP6AP1-congenital disorders of glycosylation (ATP6AP1-CDG) is a recently identified disease and rarely occurs in Asia. If a patient shows liver, neurological, and immune deficiencies, or other multisystem abnormalities, early genetic screening is advised for a definitive diagnosis. This study expands the disease spectrum of ATP6AP1-CDG and improves its understanding.