Hypertriglyceridemic Pancreatitis in a Rare Case of Type A Pyruvate Carboxylase Deficiency

Pyruvate carboxylase (PC) deficiency is a spectrum of rare autosomal recessive disorders that can have significant metabolic consequences. Decreases of PC activity limits utilization of lactate and alanine for anaplerotic and synthetic fluxes. PC deficiency can lead to hypoglycemia, lactic acidosis, and hyperammonemia. Patients can develop central nervous system disease (via glial damage and demyelination leading to hydrocephalus), hepatotoxicity and insulinopenia. The latter can result in hypertriglyceridemia, though not a hallmark of PC deficiency. Metabolic supplements help overcome defects by providing key moieties for PC function (e.g. biotin), promoting ammonia clearance (via carglumic acid), or providing substrates that are utilized independently of PC (e.g. aspartate, citrate, glutamine, and arginine). We present a case of mosaic type A PC deficiency to bring awareness to this disorder.

Case Description:

The patient was evaluated at age 21 with many complications related to PC deficiency, including recurrent VP shunt infections, leading to emergent abdominal surgery for peritonitis, shunt erosion of his sigmoid colon leading to sigmoidectomy and G/J tube placement. He was born at 38-weeks gestation with hydrocephalus, excessive sleepiness and hypotonia. He developed seizures and underwent placement of a VP shunt at age 2 to treat hydrocephalus, reducing his seizure frequency. By age 8 he had developmental delay, hepatotoxicity, bouts of lactic acidosis, and hypoglycemia. Genetics evaluated him and suspected PC deficiency. A skin fibroblast biopsy revealed 10% of expected PC function leading to a diagnosis of mosaic type A PC deficiency. He began treatment with carglumic acid, citrate, aspartic acid, biotin, arginine, and glutamine. At this admission, he presented with abdominal pain due to pancreatitis with hypertriglyceridemia of 2,529 mg/dL and chronic hyperammonemia. Due to abnormal bowel anatomy and significant illness, TPN was started. He was treated with hyperinsulinemic-euglycemic clamp which reduced triglycerides to 1,345 mg/dL. Endocrinology was consulted late in his course and recommended reduction of TPN, D5W and insulin via euglycemic clamp. His triglycerides decreased to 701 mg/dL and he was discharged. 2 weeks later he presented to the hospital with abdominal pain, and vomiting. Rifaximin was started for known pancreatitis. He developed sepsis, and worsening acidosis which led to PEA arrest. Pressors were initiated, enteral access was lost, and he was intubated. He was made comfort measures only and passed away.

Discussion:

PC deficiency is a rare disorder that can have devastating metabolic consequences. Diagnosis includes identifying clinical features, analysis of pyruvate, lactate, amino acids, and genetic testing via skin fibroblast or DNA testing. Treatments include improving activity of the urea and TCA cycles while bypassing abnormalities caused by PC deficiency. Liver transplantation may treat metabolic abnormalities with no effect on neurologic disease. In the future gene therapy may be an option. Life expectancy varies with disease severity, though few type A patients survive into adulthood.