ABSTRACT
Objective:To analyze the clinical and gene mutation characteristics of congenital disorder of glycosylation (CDG) caused by compound heterozygous mutation of the COG6 gene ( COG6-CDG). Methods:This study retrospectively analyzed the clinical data and genetic test results of a patient with COG6-CDG in Bayi Children's Hospital, the Seventh Affiliated Medical Center of Chinese PLA General Hospital, in August 2019. Literature was retrieved with keywords including COG6, COG6-CDG, congenital disorders of glycosylation typeⅡL and congenital disorders of glycosylationⅡL in China National Knowledge Infrastructure, Wanfang Database, VIP Database, PubMed, and Web of Science Database from the establishment to July 2020, to summarize the clinical and genetic characteristics of COG6-CDG. Results:(1) Case report: The 59-day-old baby boy, with a gestational age of 27 +5 weeks and birth weight of 1 180 g, presented with multi-system involvement on admission, including unidentified progressive hepatosplenomegaly with jaundice and ascites, persistent thrombocytopenia, microcephaly, hypotonia, hypohidrosis, hyperkeratosis, and recurrent hyperthermia, infection, and hypoglycemia, as well as dysfunctions of the heart, gastrointestinal tract, lungs, kidneys, ocular fundus, and the coagulation system. Despite given ventilator-assisted ventilation, anti-infection therapy, abdominal puncture and drainage, and blood transfusion, the patient still had an aggravated condition and eventually died of multiple organ failures 192 d after birth. Genetic analysis showed that the nuclear family carried compound heterozygous mutations in the COG6 gene (NM_020751.2), including missense mutations of c.662C>T(p.T221M) in exon 7 and c.443T>C(p.I148T) in exon 5, which were both novel mutations and originated from the mother and father, respectively. (2) Literature review: Eight related papers were retrieved, including 20 cases. The main manifestations were various degrees of nervous system abnormalities and growth retardation, complicated by abnormalities of the liver, heart, gastrointestinal tract, blood, immunity, teeth, and bones. All the reported cases suffered from mental and growth retardation, and nine deaths were reported. A total of 11 COG6 gene mutations were identified, and most of them were c.1167-24A>G splicing mutations in a deep intron (seven cases), followed by c.1646G>T (four cases) and c.511C>T (three cases). Conclusions:COG6-CDG commonly manifests as multi-system and multi-organ dysfunctions with poor prognosis. Gene detection is conducive to the accurate diagnosis of COG6-CDG. Our case carries compound heterozygous mutations of c.662C>T(p.T221M) and c.443T>C(p.I148T), which are unreported novel mutations.