Hepatocyte Transplant and Bridge to Subsequent Liver Transplant in an Infant with Carbamoyl Phosphate Synthetase Deficiency

Abstract

Carbamoyl phosphate synthetase 1 deficiency (CPS1D) is an autosomal recessive disorder of the urea cycle that causes hyperammonemia. Two forms of CPS1D are recognized: a lethal neonatal type and a less severe, delayed-onset type. Neonatal CPS1D cases often present their symptoms within the first days of life. Severe hyperammonemia in the neonatal period leads to serious brain damage, coma, and death if not treated promptly. We report a case of successful hepatocyte transplant and subsequent deceased donor liver transplant in an infant diagnosed with neonatal CPS1D. Hepatocytes were isolated from liver and deceased donors. At the first transplant, approximately 2.4 x 10^9 cells (7.4% of the estimated recipient's total hepatocytes) were infused over 3 sessions spanning 8 days. Hepatocytes were infused into the portal vein via an indwelling catheter inserted through the umbilical vein. After the first hepatocyte transplant, the patient showed stabilization of ammonia levels after several days and ammonia levels remained stable despite increased protein intake and discontinuation of ammonia scavengers. After 5 months, graft function seemed to deteriorate with elevated ammonia levels at times. A second hepatocyte transplant was done and was also successful in sustaining stable ammonia levels for another 5 months. The infant received deceased donor liver transplant at 13 months of age. This was the first successful hepatocyte transplant and subsequent bridge to liver transplant in a CPS1D baby in Korea. Hepatocyte transplant allowed ammonia stabilization despite protein intake, which allowed for normal growth and development in this infant.