Abstract
INTRODUCTION: Glycerol-3-phosphate dehydrogenase 1 (GPD1) deficiency is an autosomal recessive disorder causing hypertriglyceridemia, hepatomegaly, fatty liver, and hepatic fibrosis in infancy. It is an under-recognized cause of pediatric steatotic liver disease (SLD) with only 36 cases reported worldwide. METHOD: We analyzed the clinical profile of our five cases diagnosed by exome sequencing (ES) and reviewed the published cases till December 2023 using PubMed search. RESULTS: Five unrelated boys (6-24months) presented with hepatomegaly, hypertriglyceridemia, transaminase elevation, and fatty liver. ES revealed compound heterozygous mutations in two and homozygous mutation in three including two novel mutations (c.917T >C, c.905C > G). All received supportive therapy, and fenofibrate was successfully used in one case for progressive hypertriglyceridemia. Globally, 36 cases (age at diagnosis: 6 [1-164 months]) have been reported. Majority had hepatomegaly (94.4%), 22.2% each had splenomegaly and growth failure. Hypertriglyceridemia (97.2%) was nearly universal, 100% had fatty liver, and hypoglycaemia (11.2%) was uncommon. Liver biopsy (n = 18) demonstrated steatosis in all, fibrosis in 94.4%, and cirrhosis in 22.2%. During follow-up (11-376 months), hepatomegaly resolved in 35.2%, triglycerides, and transaminases normalized in 29.1% and 31.5%, respectively. No pancreatitis, cardiac events, or liver decompensation was reported. CONCLUSION: GPD1 is an uncommon cause of SLD, raised transaminases and hypertriglyceridemia in young children. Diagnosis is confirmed by genetic testing. Supportive therapy, parental counseling about the disease nature and close follow-up is recommended.