Fifteen Years of Follow-up of a Liver Transplant Recipient With Glycogen Storage Disease Type Ia (Von Gierke Disease) A.C. Maya Aparicio, C. Bernal Bellido, J. Tinoco González, S. Garcia Ruíz, L. Aguilar Romero, L.M. Marín Gómez, G. Suárez Artacho, J.M. Álamo Martínez, J. Serrano Díez-Canedo, F.J. Padillo Ruíz, and M.A. Gomez Bravo ABSTRACT Von Gierke’s disease or glycogen storage disease type Ia (GSD-Ia) is an infrequent metabolic disease caused by an atypical accumulation of glycogen. The principal cause of this pathology is deficiency of the glucose-6-phosphatase enzyme. Herein we have reported a case of a young man with a history of Von Gierke’s disease (GSD-Ia) since childhood who developed hepatocellular adenomatosis brought to light by ultrasounds and TACs. The patient began to develop early chronic renal failure, necessitating simultaneous liver and kidney transplantation. Years later continuous reviews at the nephrology and hepatobiliopancreatic surgery services show he has a good quality of life and a normal hepatorenal profile.
V
ON GIERKE’S disease or glycogen storage disease type Ia (GSD-Ia) is a rare autosomal-recessive metabolic disease (1:100,000) caused by an abnormal accumulation of glycogen. The cause of this metabolic disease is deficiency of the glucose-6-phosphatase enzyme, which is involved in the last step of the production of glucose from liver glycogen stores.1 Long-term complications include severe hypoglycemia and impaired growth. In younger children the disease typically presents with seizures and hepatomegaly manifested at 6 and 8 months.2 The disease can also cause malignant hepatic adenomas.3 CASE REPORT We report the case of a 28-year-old man with a history of Von Gierke’s disease (GSD-Ia) diagnosed in childhood, associated with chronic renal failure on hemodialysis, who developed hepatocellular adenomatosis identified at by ultrasounds and TACs (Fig 1). The patient developed early chronic renal failure and a committee of experts decided a simultaneous liver and kidney transplantation was necessary. The evolution of the patient after surgery was marked by several major bleeding episodes, controlled with transfusion-derived hematopoietic cells without the need for further surgery. The liver and renal profiles showed good analyses from the start, with diuresis normalized within weeks. He was discharged 42 days later with a normal liver profile and a creatinine level of 2.8 mg/dL. He is under regular review by the Nephrology and the Hepatobiliopancreatic Surgery services. Years later he has a good quality of life and a normal hepatorenal profile (Fig 2 and Fig 3).
Fig 1. Sample pathology: note the different hepatic adenomas.
From the General Surgery and Digestive (A.C.M.A., C.B.B., J.T.G., S.G.R., L.A.R., L.M.M.G., G.S.A., J.M.A.M., J.S.D.-C., F.J.P.R., M.A.G.B.), Hepatobiliopancreatic Surgery, Virgen del Rocio University Hospitals, Seville, Spain. Address reprint requests to A.C. Maya Aparicio, C/Cubillos No. 19, 06270, Segura de León, Badajoz. E-mail: [email protected]
0041-1345/13/$esee front matter http://dx.doi.org/10.1016/j.transproceed.2013.10.033
ª 2013 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
3668
Transplantation Proceedings, 45, 3668e3669 (2013)
GLYCOGEN STORAGE DISEASE
Fig 2. Total bilirubin (results [mg/dL] vs date).
DISCUSSION
Orthotopic liver transplantation (OLT) is now only considered in patients with GSD-Ia who do not respond to adequate dietary treatment or who developed malignant adenomas or those suggestive of malignancy. As hygienedietary treatment has resulted in the increased survival of these patients, there has been an increase in the incidence of hepatocellular carcinoma, especially among those patients with previous hepatic adenomas.4 OLT cures the disease but is accompanied by the side effects associated with sustained immunosuppression and this kind of intervention. That is why OLT is the last option in the treatment of this disease. Renal transplantation may be associated before, during, or after liver transplantation (preferably in the same procedure) if the patient has developed chronic renal failure. There are some cases reported in the medical literature showing very good results with combined hepatorenal transplantation in these patients.5e7 In conclusion, since this disease was first diagnosed, treatment has advanced by leaps and bounds, delaying OLT and improving the quality of life. An important milestone was the introduction of moist heat processed cornstarch in 2008 as a nutritional supplement, maintaining normoglycemia and even slowing the appearance of adenomas that
3669
Fig 3. Glycated hemoglobin (results [%] vs date).
necessitate transplantation. If there is associated chronic renal failure a combined hepato-renal transplantation is advisable.
REFERENCES 1. Marcolongo P, Fulceri R, Gamberucci A, et al. Multiple roles of glucose-6-phosphatases in pathophysiology: state of the art and future trends. Biochim Biophys Acta. 2013;1830(3):2608e2618. 2. Froissart R, Piraud M, Boudjemline AM, et al. Glucose-6phsphatase deficiency. Orphanet J Rare Dis. 2011;6:27. 3. Smit GPA. The longterm outcome of patients with glycogen storage disease type Ia. Eur J Pediatr. 1993;152:S52eS55. 4. Calderaro J, Labrune P, Morcrette G, et al. Molecular characterization of hepatocellular adenomas developed in patients with glycogen storage disease type I. J Hepatol. 2013 Feb;58(2): 350e357. 5. Marega A, Fregonese C, Tulissi P, et al. Preemptive liverkidney transplntation in von Gierke disease: a case report. Transplant Proc. 2011;43(4):1196e1197. 6. Carreiro G, Villela-Nogueira CA, Coelho H, et al. Orthotopic liver transplantation in glucose-6-phosphate deficience-Vin Gierke disease-with multiple hepatic adenomas and concominant focal nodular hyperplasia. J Pediatr Endocrinol Metab. 2007;20(4): 545e549. 7. Carreiro G, Villela-Nogueira CA, Coelho HU, et al. Multiple adenomas and hapatocellular carcinoma in a renal transplant patient with glycogen storage disease type 1a (von Gierke disease). Transplantation. 2001;72(2):343e344.
V
ON GIERKE’S disease or glycogen storage disease type Ia (GSD-Ia) is a rare autosomal-recessive metabolic disease (1:100,000) caused by an abnormal accumulation of glycogen. The cause of this metabolic disease is deficiency of the glucose-6-phosphatase enzyme, which is involved in the last step of the production of glucose from liver glycogen stores.1 Long-term complications include severe hypoglycemia and impaired growth. In younger children the disease typically presents with seizures and hepatomegaly manifested at 6 and 8 months.2 The disease can also cause malignant hepatic adenomas.3 CASE REPORT We report the case of a 28-year-old man with a history of Von Gierke’s disease (GSD-Ia) diagnosed in childhood, associated with chronic renal failure on hemodialysis, who developed hepatocellular adenomatosis identified at by ultrasounds and TACs (Fig 1). The patient developed early chronic renal failure and a committee of experts decided a simultaneous liver and kidney transplantation was necessary. The evolution of the patient after surgery was marked by several major bleeding episodes, controlled with transfusion-derived hematopoietic cells without the need for further surgery. The liver and renal profiles showed good analyses from the start, with diuresis normalized within weeks. He was discharged 42 days later with a normal liver profile and a creatinine level of 2.8 mg/dL. He is under regular review by the Nephrology and the Hepatobiliopancreatic Surgery services. Years later he has a good quality of life and a normal hepatorenal profile (Fig 2 and Fig 3).
Fig 1. Sample pathology: note the different hepatic adenomas.
From the General Surgery and Digestive (A.C.M.A., C.B.B., J.T.G., S.G.R., L.A.R., L.M.M.G., G.S.A., J.M.A.M., J.S.D.-C., F.J.P.R., M.A.G.B.), Hepatobiliopancreatic Surgery, Virgen del Rocio University Hospitals, Seville, Spain. Address reprint requests to A.C. Maya Aparicio, C/Cubillos No. 19, 06270, Segura de León, Badajoz. E-mail: [email protected]
0041-1345/13/$esee front matter http://dx.doi.org/10.1016/j.transproceed.2013.10.033
ª 2013 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
3668
Transplantation Proceedings, 45, 3668e3669 (2013)
GLYCOGEN STORAGE DISEASE
Fig 2. Total bilirubin (results [mg/dL] vs date).
DISCUSSION
Orthotopic liver transplantation (OLT) is now only considered in patients with GSD-Ia who do not respond to adequate dietary treatment or who developed malignant adenomas or those suggestive of malignancy. As hygienedietary treatment has resulted in the increased survival of these patients, there has been an increase in the incidence of hepatocellular carcinoma, especially among those patients with previous hepatic adenomas.4 OLT cures the disease but is accompanied by the side effects associated with sustained immunosuppression and this kind of intervention. That is why OLT is the last option in the treatment of this disease. Renal transplantation may be associated before, during, or after liver transplantation (preferably in the same procedure) if the patient has developed chronic renal failure. There are some cases reported in the medical literature showing very good results with combined hepatorenal transplantation in these patients.5e7 In conclusion, since this disease was first diagnosed, treatment has advanced by leaps and bounds, delaying OLT and improving the quality of life. An important milestone was the introduction of moist heat processed cornstarch in 2008 as a nutritional supplement, maintaining normoglycemia and even slowing the appearance of adenomas that
3669
Fig 3. Glycated hemoglobin (results [%] vs date).
necessitate transplantation. If there is associated chronic renal failure a combined hepato-renal transplantation is advisable.
REFERENCES 1. Marcolongo P, Fulceri R, Gamberucci A, et al. Multiple roles of glucose-6-phosphatases in pathophysiology: state of the art and future trends. Biochim Biophys Acta. 2013;1830(3):2608e2618. 2. Froissart R, Piraud M, Boudjemline AM, et al. Glucose-6phsphatase deficiency. Orphanet J Rare Dis. 2011;6:27. 3. Smit GPA. The longterm outcome of patients with glycogen storage disease type Ia. Eur J Pediatr. 1993;152:S52eS55. 4. Calderaro J, Labrune P, Morcrette G, et al. Molecular characterization of hepatocellular adenomas developed in patients with glycogen storage disease type I. J Hepatol. 2013 Feb;58(2): 350e357. 5. Marega A, Fregonese C, Tulissi P, et al. Preemptive liverkidney transplntation in von Gierke disease: a case report. Transplant Proc. 2011;43(4):1196e1197. 6. Carreiro G, Villela-Nogueira CA, Coelho H, et al. Orthotopic liver transplantation in glucose-6-phosphate deficience-Vin Gierke disease-with multiple hepatic adenomas and concominant focal nodular hyperplasia. J Pediatr Endocrinol Metab. 2007;20(4): 545e549. 7. Carreiro G, Villela-Nogueira CA, Coelho HU, et al. Multiple adenomas and hapatocellular carcinoma in a renal transplant patient with glycogen storage disease type 1a (von Gierke disease). Transplantation. 2001;72(2):343e344.
