Title: Outcomes of Liver Transplantation in Glycogen Storage Disease Type Ib
Biochemical/Metabolic and Therapeutics
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Primary Categories:
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Secondary Categories:
Introduction:
Glycogen Storage Disease type Ib (GSD Ib) is caused by a defect in a glucose-6-phoshate transporter SLC37A4, disrupting glycogenolysis and gluconeogenesis. Affected individuals present with hypoglycemia, lactic acidosis, hyperuricemia, neutropenia, and impaired neutrophil function. The disease sequalae includes severe recurrent infections, inflammatory bowel disease (IBD), hepatic adenomas (HAs) with risk for malignant transformation, and chronic kidney disease (CKD). Dietary management with continuous feeds and/or uncooked cornstarch (UCCS) supplementation is used to prevent hypoglycemia and maintain metabolic control. Liver transplantation has been recommended for patients with rapidly growing HAs and/or poor metabolic control, and is typically combined with kidney transplantation for those with CKD.
Methods:
We present two molecularly-confirmed GSD Ib patients who underwent a liver and a combined liver-kidney transplantation, respectively, in early adulthood. A retrospective chart review was conducted to evaluate their clinical course pre- and post-transplantation.
Results:
Patient # 1
A 45-year-old male with GSD Ib received a liver transplant at age 29 years. His pre-transplant course included frequent episodes of hypoglycemia, HAs, brain abscess, seizures, gout, pancreatitis, epistaxis, anemia, osteoporosis, IBD, and numerous infections. He was initially managed with continuous feeds, later replaced by UCCS with simple sugar restrictions, along with granulocyte colony stimulating factor (G-CSF), allopurinol, and potassium citrate. Notably, his kidney function was normal prior to liver transplantation. He underwent an uncomplicated liver transplant (listed with MELD score 6) due to the presence of multiple HAs, and poor metabolic control. He discontinued cornstarch therapy and dietary restrictions, and expressed a better quality of life. Despite these improvements, he has continued to experience recurrent seizures (albeit less severe than before), gout, CKD stage III (likely due to calcineurin inhibitor toxicity and progressive GSD I nephropathy), neutropenia, and recurrent infections.
Patient # 2
A 41-year-old female with GSD Ib underwent combined liver-kidney transplantation at age 18 years. Her pre-transplant course was notable for hypoglycemia, cardiac arrest at age 5 years (due to hypoglycemia), short stature, gout, hyperlipidemia, pancreatitis, HAs, renal failure requiring peritoneal dialysis, anemia, osteoporosis, infections, neutropenia, and IBD requiring subtotal colectomy. She was managed with UCCS, dietary restrictions, allopurinol, and G-CSF. Combined liver and kidney transplantation was recommended due to multiple HAs, poor metabolic control, and CKD. She was listed with a MELD score of 20. There were no peri-surgical complications. Since the transplantations, she has not required dialysis, dietary restrictions, or cornstarch therapy. However, she developed nephrolithiasis, recurrent urinary tract infections, IBD, severe neutropenia (managed with G-CSF), anemia, depression, and chronic pain. Her kidney function remains stable.
Conclusion:
Currently, liver transplantation is the only curative treatment option for GSD Ib liver disease. While it corrects hypoglycemia and eliminates the need for dietary management, neutropenia persists. Following the transplantation, both of our patients continued to experience frequent infections, IBD, and persistent neutropenia resulting in continued need for G-CSF. Moreover, if the liver transplant is not combined with the kidney transplant, anti-rejection regimens may further contribute to kidney damage, and worsening hyperuricemia, as demonstrated in patient #1. Early diagnosis and treatment have significantly improved outcomes in patients with GSD Ib, yet some cases will require liver and/or kidney transplantation. When clinically indicated, the transplants should be performed in experienced centers of excellence. When the HAs are seen in GSDs, application of the MELD exception should be considered to allow the patients be adequately prioritized on the waiting list. While we demonstrate successful management of the liver disease in both patients, long-term post-transplant surveillance (including assessment of neutrophils and renal function) is recommended as liver transplantation often does not correct the extrahepatic manifestations of the disease (renal, neutrophil dysfunction).
Glycogen Storage Disease type Ib (GSD Ib) is caused by a defect in a glucose-6-phoshate transporter SLC37A4, disrupting glycogenolysis and gluconeogenesis. Affected individuals present with hypoglycemia, lactic acidosis, hyperuricemia, neutropenia, and impaired neutrophil function. The disease sequalae includes severe recurrent infections, inflammatory bowel disease (IBD), hepatic adenomas (HAs) with risk for malignant transformation, and chronic kidney disease (CKD). Dietary management with continuous feeds and/or uncooked cornstarch (UCCS) supplementation is used to prevent hypoglycemia and maintain metabolic control. Liver transplantation has been recommended for patients with rapidly growing HAs and/or poor metabolic control, and is typically combined with kidney transplantation for those with CKD.
Methods:
We present two molecularly-confirmed GSD Ib patients who underwent a liver and a combined liver-kidney transplantation, respectively, in early adulthood. A retrospective chart review was conducted to evaluate their clinical course pre- and post-transplantation.
Results:
Patient # 1
A 45-year-old male with GSD Ib received a liver transplant at age 29 years. His pre-transplant course included frequent episodes of hypoglycemia, HAs, brain abscess, seizures, gout, pancreatitis, epistaxis, anemia, osteoporosis, IBD, and numerous infections. He was initially managed with continuous feeds, later replaced by UCCS with simple sugar restrictions, along with granulocyte colony stimulating factor (G-CSF), allopurinol, and potassium citrate. Notably, his kidney function was normal prior to liver transplantation. He underwent an uncomplicated liver transplant (listed with MELD score 6) due to the presence of multiple HAs, and poor metabolic control. He discontinued cornstarch therapy and dietary restrictions, and expressed a better quality of life. Despite these improvements, he has continued to experience recurrent seizures (albeit less severe than before), gout, CKD stage III (likely due to calcineurin inhibitor toxicity and progressive GSD I nephropathy), neutropenia, and recurrent infections.
Patient # 2
A 41-year-old female with GSD Ib underwent combined liver-kidney transplantation at age 18 years. Her pre-transplant course was notable for hypoglycemia, cardiac arrest at age 5 years (due to hypoglycemia), short stature, gout, hyperlipidemia, pancreatitis, HAs, renal failure requiring peritoneal dialysis, anemia, osteoporosis, infections, neutropenia, and IBD requiring subtotal colectomy. She was managed with UCCS, dietary restrictions, allopurinol, and G-CSF. Combined liver and kidney transplantation was recommended due to multiple HAs, poor metabolic control, and CKD. She was listed with a MELD score of 20. There were no peri-surgical complications. Since the transplantations, she has not required dialysis, dietary restrictions, or cornstarch therapy. However, she developed nephrolithiasis, recurrent urinary tract infections, IBD, severe neutropenia (managed with G-CSF), anemia, depression, and chronic pain. Her kidney function remains stable.
Conclusion:
Currently, liver transplantation is the only curative treatment option for GSD Ib liver disease. While it corrects hypoglycemia and eliminates the need for dietary management, neutropenia persists. Following the transplantation, both of our patients continued to experience frequent infections, IBD, and persistent neutropenia resulting in continued need for G-CSF. Moreover, if the liver transplant is not combined with the kidney transplant, anti-rejection regimens may further contribute to kidney damage, and worsening hyperuricemia, as demonstrated in patient #1. Early diagnosis and treatment have significantly improved outcomes in patients with GSD Ib, yet some cases will require liver and/or kidney transplantation. When clinically indicated, the transplants should be performed in experienced centers of excellence. When the HAs are seen in GSDs, application of the MELD exception should be considered to allow the patients be adequately prioritized on the waiting list. While we demonstrate successful management of the liver disease in both patients, long-term post-transplant surveillance (including assessment of neutrophils and renal function) is recommended as liver transplantation often does not correct the extrahepatic manifestations of the disease (renal, neutrophil dysfunction).