Novel missense variants inPCK1gene cause cytosolic PEPCK deficiency with growth failure from inadequate caloric intake

Cytosolic PEPCK deficiency (PCKDC) is a rare autosomal recessive inborn error of metabolism, which can present with hypoglycemia, lactic acidosis, and liver failure. It is caused by biallelic pathogenic variants in thePCK1gene. Only fourPCK1variants have been previously reported in seven patients with PCKDC, and their clinical course of this condition has not been well characterized. Here, we report a Hispanic male with novel biallelicPCK1variants, p.(Gly430Asp) and p.(His496Gln), who had a unique clinical presentation. He presented with a new onset of growth failure, elevated blood lactate, transaminitis, and abnormal urine metabolites profile, but he has not had documented hypoglycemia. Growth restriction happened due to insufficient caloric intake, and it was improved with nutritional intervention. PCKDC is a manageable disorder and therefore appropriate nutritional and clinical suspicion from typical lab abnormalities which lead to molecular confirmation tests are essential to prevent poor clinical outcomes.

Automated summary

Cytosolic PEPCK deficiency (PCKDC) is a rare autosomal recessive inborn error of metabolism characterized by hypoglycemia, lactic acidosis, and liver failure. Nutritional intervention can improve growth restriction symptoms, and timely clinical monitoring and molecular testing are crucial for preventing poor clinical outcomes.