- Email: [email protected]
Simultaneous liver-kidney transplantation for glycogen storage disease type IA (von Gierke's disease)
Simultaneous Liver-Kidney Transplantation for Glycogen Storage Disease Type Ia (von Gierke’s Disease) F. Panaro, E. Andorno, G. Basile, N. Morelli, G. Bottino, I. Fontana, M. Bertocchi, S. DiDomenico, M. Miggino, L. Saltalamacchia, D. Ghinolfi, L. Bonifazio, T.M. Jarzembowski, and U. Valente ABSTRACT Introduction. Glycogen storage disease type Ia (GSDIa) is due to the deficiency of glucose-6-phosphatase activity in the liver, kidney, and intestine. Although significant progress has been achieved in the management of patients with GSDIa, complications still emerge. The potential for development of liver adenomatosis and kidney failure makes these patients candidates for simultaneous liver-kidney transplantation (SLKT). Herein, we describe such a transplantation in a patient affected by this rare storage disease. Methods. A 25-year-old female patient with GSDIa developed hepatic adenoma and kidney failure despite dietary therapy. The patient underwent an SLKT from a cadaveric donor. Results. The operative time was 8 hours without hemotransfusion. Only a transitory lactic acidosis was observed. Laboratory results normalized on postoperative day 7. The patient was discharged on postoperative day 9. After 4 months, the patient is in good condition with well-functioning kidney and liver allografts. Conclusion. Patients with end-stage renal disease secondary to GSDIa should be considered for SLKT, especially when the disease is in an early stage.
G
LYCOGEN STORAGE DISEASES are inherited disorders in which the concentration and structure of glycogen is abnormal in body tissues. Glycogen storage disease type I has an estimated frequency among newborns of 1 in 100,000.1,2 Therefore, no single metabolic center has a large series of these patients. There is a relative paucity of data regarding outcomes; indeed all of the reports focus on young patients.3–5 Glycogen storage disease type Ia (GSDIa), or von Gierke’s disease, is caused by a deficiency of glucose 6-phosphatase activity.2 The clinical manifestations are growth retardation, hepatomegaly, hypoglycemia, lactic acidemia, hyperuricemia, and hyperlipidemia. Long-term complications include gout, renal disease, pulmonary hypertension, and hepatic adenomas, which may undergo malignant transformation.1,6 In this setting, orthotopic liver transplantation (OLT) is the only therapeutic option when metastases are not present.4,5,7 Although liver transplant corrects the glucose homeostasis, it does not prevent the development of renal failure. Moreover, the immunosuppression can, in fact, worsen renal function due to calcineurin inhibitor (CI) nephrotoxicity.8,9 Progressive renal deterioration secondary to GSDIa begins in the first years of life and is silent for many years.1 In
this report, we describe the management, clinical course, and outcome of a GSDIa patient who underwent simultaneous liver-kidney transplantation (SLKT). CASE REPORT A 25-year-old woman developed end-stage liver disease (ESLD) secondary to GSDIa followed by development of hepatic adenomatosis (see Fig 1) and kidney failure 10 years after dietary therapy. The patient was hemodialyzed for 17 months. Finally, a cadaveric donor became available. The patient underwent simultaneous liver (weight: 850 g) and kidney transplantation from a 13-year-old, heart-beating donor who was brain-dead due to a head injury and cerebral bleed. The donor hepatectomy and recipient From the Department of General and Transplant Surgery (F.P., E.A., N.M., G.B., I.F., M.B., S.D., M.M., L.S., D.G., L.B., U.V.) St. Martino Hospital, University of Genoa, Genoa, Italy; University of Genoa; “G. Gaslini Children Hospital” (G.B.) Pediatric Division, Genoa, Italy; and University of Illinois at Chicago (T.M.J.), Department of Surgery, Division of Transplantation, Chicago, Illinois, USA. Address reprint requests to F. Panaro, MD, Department of General and Transplant Surgery, St Martino Hospital-University of Genoa, Largo Rosanna Benzi 10, Genoa 16100, Italy. E-mail: [email protected]
© 2004 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/04/$–see front matter doi:10.1016/j.transproceed.2004.05.070
Transplantation Proceedings, 36, 1483–1484 (2004)
1483
1484
Fig 1.
PANARO, ANDORNO, BASILE ET AL
Recipient’s liver after hepatectomy. Note adenomatosis.
operations were performed as described previously.4 –7 The recipient hepatectomy preserved the vena cava. The graft vena cava was anastomosed to the recipient vena cava using a “piggyback” technique. Anastomosis of the recipient’s portal vein to the graft portal vein was made in end-to-end fashion. Hepatic arterial reconstruction was performed under microscopic observation in end-to-end fashion between the graft proper hepatic artery and the recipient common hepatic artery. Anastomosis of the bile duct was performed as an end-to-end anastomosis without a T-tube. The kidney was implanted separately through a lower abdominal extraperitoneal incision using the standard technique. The operative time was 8 hours: 5 hours for the liver and 3 hours for the kidney without hemotransfusion. An intraoperative lactic acidosis was the only parameter noticed to be elevated (lactic acid 22 mmol/L). The patient was extubated on the first postoperative day. The immunosuppressive regimen included cyclosporine (CsA) and steroids. CsA trough levels were maintained at therapeutic ranges and the renal function was monitored. No acute rejection episode was observed. Laboratory results normalized by postoperative day 7. The patient was discharged on postoperative day 9 with following lab results: WBC 10,900/mm3, creatinine 1.2 mg/dL; SGOT 42 U/L; SGPT 99 U/L; total bilirubin 1.0 mg/dL. At 4-month follow-up, the patient is in good general condition with both grafts functional (creatinine 1.08 mg/dL; uricemia 6.6 mg/dL; SGOT 62 U/L; SGPT 170 U/L, total bilirubin 0.73 mg/dL, PT 109%).
DISCUSSION
To date, OLT has been reported in 17 patients with GSDIa and in two patients with GSD Ib.2,3,9 In most cases, the OLT was performed due to multiple hepatic adenomas. In terms of short-term follow-up, all reports show that OLT corrects the hepatic enzyme defect, providing an improvement in both metabolic disturbances and quality of life.4,5,7,9 However, only a few reports describe long-term follow-up after OLT. Selby et al reported one patient who developed renal failure 9 years
after OLT;10 Koestinger et al reported a patient in good health 2 years after OLT with no indication of poor renal function.11 It appears that long-term outcomes in these patients may be compromised by several complications. Furthermore, long-term complications of OLT and immunosuppressive posttransplant regimens, particularly in children, are not yet fully understood. Thus the mortality and morbidity secondary to transplantation have to be considered.4,9,12 Although the indications for OLT appear to be clear, the dilemma of renal transplant is continuously debated. Faivre et al observed that post-OLT one patient developed glomerulosclerosis associated with GSDIa.4 Therefore, a potential transplant candidate should undergo a careful and detailed renal evaluation prior to transplantation. Selby et al reported no renal involvement in a patient post-SLKT more than 10 years after the first OLT.10 Nevertheless, it is not clear whether OLT may reverse and/or prevent renal disease in GSDIa patients.5 In addition, CI nephrotoxic effects may also complicate this setting.8,12 More than 10 GSDIa patients have received renal transplants; however, only two cases have been reported in the literature.5,9 In both cases, renal transplantation failed to improve the glucose metabolism. Finally, only two GSDIa patients have undergone SLKT.9 In conclusion, GSDIa patients should be treated with OLT when adenomas are unresectable and present clinical and histological signs of malignant transformation. Furthermore, severe retarded growth and/or hyperlipidemia that does not respond to appropriate therapy may be potential indications for OLT. Renal transplantation, on the other hand, is indicated when renal involvement has evolved to terminal renal failure. However, if OLT is indicated for a GSDIa patient, SLKT may be indicated since the slow progressing renal dysfunction will progress to ESRD. REFERENCES 1. Rake JP, Visser G, Labrune P, et al: Eur J Pediatr 161:S112, 2002 2. Matern D, Seydewitz HH, Bali D, et al: Eur J Pediatr 161(Suppl 1):S10, 2002 3. Rake JP, Visser G, Labrune P, et al: Eur J Pediatr 161:S20, 2002 4. Faivre L, Houssin D, Valayer J, et al: J Inherit Metab Dis 22:723, 1999 5. Labrune P: Eur J Pediatr 161(Suppl 1):S53, 2002 6. Lerut JP, Ciccarelli O, Sempoux C, et al: Transpl Int 16:879, 2003 7. Matern D, Starzl TE, Arnaout W, et al: Eur J Pediatr 158(Suppl 2):S43, 1999 8. Ziolkowski J, Paczek L, Senatorski G, et al: Transplant Proc 35:2307, 2003 9. Becker T, Nyibata M, Lueck R, et al: Liver Transplantation 9:1067, 2003 10. Selby R, Starzl TE, Yunis E, et al: Eur J Pedriat 152(Suppl 1):S71, 1993 11. Koestinger A, Gillet M, Chiolero R, et al: Transplantation 69:2205, 2000 12. Gonwa TA, Mai ML, Klintmaln GB: N Engl J Med 349: 2563, 2003
G
LYCOGEN STORAGE DISEASES are inherited disorders in which the concentration and structure of glycogen is abnormal in body tissues. Glycogen storage disease type I has an estimated frequency among newborns of 1 in 100,000.1,2 Therefore, no single metabolic center has a large series of these patients. There is a relative paucity of data regarding outcomes; indeed all of the reports focus on young patients.3–5 Glycogen storage disease type Ia (GSDIa), or von Gierke’s disease, is caused by a deficiency of glucose 6-phosphatase activity.2 The clinical manifestations are growth retardation, hepatomegaly, hypoglycemia, lactic acidemia, hyperuricemia, and hyperlipidemia. Long-term complications include gout, renal disease, pulmonary hypertension, and hepatic adenomas, which may undergo malignant transformation.1,6 In this setting, orthotopic liver transplantation (OLT) is the only therapeutic option when metastases are not present.4,5,7 Although liver transplant corrects the glucose homeostasis, it does not prevent the development of renal failure. Moreover, the immunosuppression can, in fact, worsen renal function due to calcineurin inhibitor (CI) nephrotoxicity.8,9 Progressive renal deterioration secondary to GSDIa begins in the first years of life and is silent for many years.1 In
this report, we describe the management, clinical course, and outcome of a GSDIa patient who underwent simultaneous liver-kidney transplantation (SLKT). CASE REPORT A 25-year-old woman developed end-stage liver disease (ESLD) secondary to GSDIa followed by development of hepatic adenomatosis (see Fig 1) and kidney failure 10 years after dietary therapy. The patient was hemodialyzed for 17 months. Finally, a cadaveric donor became available. The patient underwent simultaneous liver (weight: 850 g) and kidney transplantation from a 13-year-old, heart-beating donor who was brain-dead due to a head injury and cerebral bleed. The donor hepatectomy and recipient From the Department of General and Transplant Surgery (F.P., E.A., N.M., G.B., I.F., M.B., S.D., M.M., L.S., D.G., L.B., U.V.) St. Martino Hospital, University of Genoa, Genoa, Italy; University of Genoa; “G. Gaslini Children Hospital” (G.B.) Pediatric Division, Genoa, Italy; and University of Illinois at Chicago (T.M.J.), Department of Surgery, Division of Transplantation, Chicago, Illinois, USA. Address reprint requests to F. Panaro, MD, Department of General and Transplant Surgery, St Martino Hospital-University of Genoa, Largo Rosanna Benzi 10, Genoa 16100, Italy. E-mail: [email protected]
© 2004 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/04/$–see front matter doi:10.1016/j.transproceed.2004.05.070
Transplantation Proceedings, 36, 1483–1484 (2004)
1483
1484
Fig 1.
PANARO, ANDORNO, BASILE ET AL
Recipient’s liver after hepatectomy. Note adenomatosis.
operations were performed as described previously.4 –7 The recipient hepatectomy preserved the vena cava. The graft vena cava was anastomosed to the recipient vena cava using a “piggyback” technique. Anastomosis of the recipient’s portal vein to the graft portal vein was made in end-to-end fashion. Hepatic arterial reconstruction was performed under microscopic observation in end-to-end fashion between the graft proper hepatic artery and the recipient common hepatic artery. Anastomosis of the bile duct was performed as an end-to-end anastomosis without a T-tube. The kidney was implanted separately through a lower abdominal extraperitoneal incision using the standard technique. The operative time was 8 hours: 5 hours for the liver and 3 hours for the kidney without hemotransfusion. An intraoperative lactic acidosis was the only parameter noticed to be elevated (lactic acid 22 mmol/L). The patient was extubated on the first postoperative day. The immunosuppressive regimen included cyclosporine (CsA) and steroids. CsA trough levels were maintained at therapeutic ranges and the renal function was monitored. No acute rejection episode was observed. Laboratory results normalized by postoperative day 7. The patient was discharged on postoperative day 9 with following lab results: WBC 10,900/mm3, creatinine 1.2 mg/dL; SGOT 42 U/L; SGPT 99 U/L; total bilirubin 1.0 mg/dL. At 4-month follow-up, the patient is in good general condition with both grafts functional (creatinine 1.08 mg/dL; uricemia 6.6 mg/dL; SGOT 62 U/L; SGPT 170 U/L, total bilirubin 0.73 mg/dL, PT 109%).
DISCUSSION
To date, OLT has been reported in 17 patients with GSDIa and in two patients with GSD Ib.2,3,9 In most cases, the OLT was performed due to multiple hepatic adenomas. In terms of short-term follow-up, all reports show that OLT corrects the hepatic enzyme defect, providing an improvement in both metabolic disturbances and quality of life.4,5,7,9 However, only a few reports describe long-term follow-up after OLT. Selby et al reported one patient who developed renal failure 9 years
after OLT;10 Koestinger et al reported a patient in good health 2 years after OLT with no indication of poor renal function.11 It appears that long-term outcomes in these patients may be compromised by several complications. Furthermore, long-term complications of OLT and immunosuppressive posttransplant regimens, particularly in children, are not yet fully understood. Thus the mortality and morbidity secondary to transplantation have to be considered.4,9,12 Although the indications for OLT appear to be clear, the dilemma of renal transplant is continuously debated. Faivre et al observed that post-OLT one patient developed glomerulosclerosis associated with GSDIa.4 Therefore, a potential transplant candidate should undergo a careful and detailed renal evaluation prior to transplantation. Selby et al reported no renal involvement in a patient post-SLKT more than 10 years after the first OLT.10 Nevertheless, it is not clear whether OLT may reverse and/or prevent renal disease in GSDIa patients.5 In addition, CI nephrotoxic effects may also complicate this setting.8,12 More than 10 GSDIa patients have received renal transplants; however, only two cases have been reported in the literature.5,9 In both cases, renal transplantation failed to improve the glucose metabolism. Finally, only two GSDIa patients have undergone SLKT.9 In conclusion, GSDIa patients should be treated with OLT when adenomas are unresectable and present clinical and histological signs of malignant transformation. Furthermore, severe retarded growth and/or hyperlipidemia that does not respond to appropriate therapy may be potential indications for OLT. Renal transplantation, on the other hand, is indicated when renal involvement has evolved to terminal renal failure. However, if OLT is indicated for a GSDIa patient, SLKT may be indicated since the slow progressing renal dysfunction will progress to ESRD. REFERENCES 1. Rake JP, Visser G, Labrune P, et al: Eur J Pediatr 161:S112, 2002 2. Matern D, Seydewitz HH, Bali D, et al: Eur J Pediatr 161(Suppl 1):S10, 2002 3. Rake JP, Visser G, Labrune P, et al: Eur J Pediatr 161:S20, 2002 4. Faivre L, Houssin D, Valayer J, et al: J Inherit Metab Dis 22:723, 1999 5. Labrune P: Eur J Pediatr 161(Suppl 1):S53, 2002 6. Lerut JP, Ciccarelli O, Sempoux C, et al: Transpl Int 16:879, 2003 7. Matern D, Starzl TE, Arnaout W, et al: Eur J Pediatr 158(Suppl 2):S43, 1999 8. Ziolkowski J, Paczek L, Senatorski G, et al: Transplant Proc 35:2307, 2003 9. Becker T, Nyibata M, Lueck R, et al: Liver Transplantation 9:1067, 2003 10. Selby R, Starzl TE, Yunis E, et al: Eur J Pedriat 152(Suppl 1):S71, 1993 11. Koestinger A, Gillet M, Chiolero R, et al: Transplantation 69:2205, 2000 12. Gonwa TA, Mai ML, Klintmaln GB: N Engl J Med 349: 2563, 2003