Advertisement

Metabolic Disorders in the Liver

  • Masaki IwaiEmail author
  • Atsushi Kitamura
  • Hajime Isomoto
  • Yutaka Horie
  • Wilson M. S. Tsui
Chapter

Abstract

Iron overload, or siderosis, is a commonly encountered problem in clinical practice and may be classified as primary (genetic) or secondary to other diseases, such as hereditary anemias (Table 12.1). Dietary iron is absorbed primarily by enterocytes in the duodenum, transported from the intestine to the portal blood stream (where it is bound to apotransferrin), and transported to the liver. It is, therefore, not surprising that excessive deposition of iron in liver is commonly encountered in liver biopsies.

Keywords

Iron overload Hereditary hemochromatosis Secondary hemochromatosis Transfusion iron overload Liver fibrosis Differential diagnosis of hemochromatosis Wilson’s disease Non-Wilson’s disease form of copper toxicosis Indian childhood cirrhosis Idiopathic copper toxicosis Menkes disease Porphyria Acute intermittent porphyria Cutaneous porphyria Amyloidosis Anorexia nervosa Glycogen storage disease Citrullinemia 

Abbreviations

AIP

Acute intermittent porphyria

ALA

δ-aminolevulinic acid

ALP

Alkaline phosphatase

ATP7B

Adenosine triphospholic acid 7B

CTLN2

Adult-onset type II citrullinemia

EPP

Erythropoietic protoporphyria

FTTDCD

Failure to thrive and dyslipidemia caused by citrin deficiency

HH

Hereditary hemochromatosis

HLA

Human leukocyte antigen

LSCs

Liver stellate cells

NADH

Reduced nicotinamide adenine dinucleotide

NICCD

Neonatal intrahepatic cholestasis caused by citrin deficiency

PBG

Porphobilinogen

PCT

Porphyria cutanea tarda

TfR2

Transferrin receptor 2

Notes

Acknowledgments

Emeritus Professor Hisao Hayashi in Aichi Gakuin University School of Pharmacy and Dr. Hironori Mitsuyoshi in Kyoto Chubu Medical Center are acknowledged for their help in editing content of hemochromatosis and Wilson’s or other copper-related diseases.

References

  1. 1.
    Powell LW, Kerr JF. The pathology of the liver in hemochromatosis. Pathobiol Anu. 1975;5:317–37.Google Scholar
  2. 2.
    Niederau C, Fischer R, Sonnenberg A, Stremmel W, Trampisch HJ, Strohmeyer G. Survival and causes of death in cirrhotic and noncirrhotic patients with primary hemochromatosis. N Engl J Med. 1985;313:1256–62.PubMedGoogle Scholar
  3. 3.
    Feder JN, Gnirke A, Thomas W, et al. A novel MHC class I-like gene is mutated in patients with hereditary hemochromatosis. Nat Genet. 1996;13:399–408.PubMedGoogle Scholar
  4. 4.
    Pietrangelo A. Non-HFE hemochromatosis. Semin Liver Dis. 2005;25:450–60.PubMedGoogle Scholar
  5. 5.
    Létocart E, Le Gac G, Majore S, et al. A novel missense mutation in SLC40A1 results in resistance to hepcidin and confirms the existence of two ferroportin-associated iron overload diseases. Br J Haematol. 2009;147:379–85.PubMedGoogle Scholar
  6. 6.
    Pietrangelo A. Genetics, genetic testing, and management of hemochromatosis. Gastroenterology. 2015;149:1240–51.PubMedGoogle Scholar
  7. 7.
    Hussain SP, Raja K, Amstad PA, Sawyer M, Trudel LJ, Wogan GN, Hofseth LJ, Shields PG, Billiar TR, Trautwein C, Hohler T, Galle PR, Phillips DH, Markin R, Marrogi AJ, Harris CC. Increased p53 mutation load in nontumorous human liver of Wilson disease and hemochromatosis: oxyradical overload diseases. Proc Natl Acad Sci U S A. 2000;97:12770–5.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Tsui WM, Lam PW, Lee KC, Ma KF, Chan YK, Wong MW, et al. The C282Y mutation of the HFE gene is not found in Chinese haemochromatotic patients: multicentre retrospective study. Hong Kong Med J. 2000;6:153–8.PubMedGoogle Scholar
  9. 9.
    Wonke B, Hoffbrand AV, Brown D, Dusheiko G. Antibody to hepatitis C virus in multiply transfused patients with thalassaemia major. J Clin Pathol. 1990;43:638–40.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Kaji K, Nakanuma Y, Sasaki M, Unoura M, Kobayashi K, Nonomura A. Hemosiderin deposition in portal endothelial cells: a novel hepatic hemosiderosis frequent in chronic viral hepatitis B and C. Human Pathol. 1995;26:1080–5.Google Scholar
  11. 11.
    Kothari T, Swamy AP, Lee JC, Mangla JC, Cestero RV. Hepatic hemosiderosis in maintenance hemodialysis (MHD) patients. Dig Dis Sci. 1980;25:363–8.PubMedGoogle Scholar
  12. 12.
    Schafer AI, Cheron RG, Dluhy R, Cooper B, Gleason RE, Soeldner JS, et al. Clinical consequences of acquired transfusional iron overload in adults. N Engl J Med. 1981;304:319–24.PubMedGoogle Scholar
  13. 13.
    Ali M, Fayemi AO, Rigolosi R, Frascino J, Marsden T, Malcolm D. Hemosiderosis in hemodialysis patients. An autopsy study of 50 cases. JAMA. 1980;244:343–5.PubMedGoogle Scholar
  14. 14.
    Carthew P, Dorman BM, Edwards RE, Francis JE, Smith AG. A unique rodent model for both the cardiotoxic and hepatotoxic effects of prolonged iron overload. Lab Investig. 1993;69:217–22.PubMedGoogle Scholar
  15. 15.
    de Leeuw AM, McCarthy SP, Geerts A, Knook DL. Purified rat liver fat-storing cells in culture divide and contain collagen. Hepatology. 1984;4:392–403.PubMedGoogle Scholar
  16. 16.
    Ramm GA, Li SC, Li L, Britton RS, O’Neill R, Kobayashi Y, et al. Chronic iron overload causes activation of rat lipocytes in vivo. Am J Phys. 1995;268(3 Pt 1):G451–8.Google Scholar
  17. 17.
    Akalli O, Ropraz P, Trzeciak A, Benzonana G, Gillessen D, Gabbiani G. A monoclonal antibody against α-smooth muscle actin: a new probe for smooth muscle differentiation. J Cell Biol. 1986;103:2787–96.Google Scholar
  18. 18.
    Chezmar JL, Nelson RC, Malko JA, Bernardino ME. Hepatic iron overload; diagnosis and quantification by noninvasive imaging. Gastrointest Radiol. 1990;15:27–31.PubMedGoogle Scholar
  19. 19.
    Howard JM, Ghent CN, Valberg LS. Diagnostic efficacy of hepatic computed tomography in the detection of body iron overload. Gastroenterology. 1983;84:209–15.PubMedGoogle Scholar
  20. 20.
    Miller FH, Fisher MR, Soper W, Gore RM. MRI of hepatic iron deposition in patients with renal transplant. Gastrointest Radiol. 1991;16:229–33.PubMedGoogle Scholar
  21. 21.
    Stål P. Iron as a hepatotoxin. Dig Dis Sci. 1995;13:205–22.Google Scholar
  22. 22.
    Bacon BR, Britton RS. The pathology of hepatic iron overload: a free radical-mediated process? Hepatology. 1990;11:127–37.PubMedGoogle Scholar
  23. 23.
    Bacon BR, Tavill AS, Brittenham GM, Park CH, Recknagel RP. Hepatic 1ipid peroxidation in vivo in rats with chronic iron overload. J Clin Invest. 1983;71:429–39.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Yokoi Y, Namihisa T, Matsuzaki A, Yamaguchi Y. Distribution of Ito cells in experimental hepatic fibrosis. Liver. 1988;8:48–52.PubMedGoogle Scholar
  25. 25.
    Enzan H, Himeno H, Iwamura S, Saibara T, Ohnishi S, Yamamoto Y, et al. Sequential changes in human Ito cells and their relation to postnecrotic liver fibrosis in massive and submassive hepatic necrosis. Virchows Arch. 1995;426:95–101.PubMedGoogle Scholar
  26. 26.
    Schmitt-Graff A, Kruger S, Bochard F, Gabbiani G, Denk H. Modulation of alpha smooth muscle actin and desmin expression in perisinusoidal cells of normal and diseased human livers. Am J Pathol. 1991;138:1233–42.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Britton RS, Ramm GA, Olynyk J, Singh R, O’Neil R, Bacon BR. Pathophysiology of iron toxicity. Adv Exp Med Biol. 1994;356:239–53.PubMedGoogle Scholar
  28. 28.
    Ludwig JL, Hashimoto E, Porayko MK, Moyer TP, Baldus WP. Hemosiderosis in cirrhosis: a study of 447 native livers. Gastroenterology. 1997;112:882–8.PubMedGoogle Scholar
  29. 29.
    Grove J, Daly AK, Burt AD, Guzall M, James OF, Bassendine MF, et al. Heterozygotes for HFE mutations have no increased risk of advanced alcoholic liver diseases. Gut. 1998;43:262–6.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Bonkovsky HL, Jawaid Q, Tortorelli K, LeClair P, Cobb J, Lambrecht RW, et al. Non-alcoholic steatohepatitis and iron: increased prevalence of mutations of the HFE gene in non-alcoholic steatohepatitis. J Hepatol. 1999;31:421–9.PubMedGoogle Scholar
  31. 31.
    Bugianesi E, Manzini P, D’Antico S, Vanni E, Longo F, Leone N, et al. Relative contribution of iron burden, HFE mutations, and insulin resistance to fibrosis in nonalcoholic fatty liver. Hepatology. 2004;39:179–87.PubMedGoogle Scholar
  32. 32.
    Riordan SM, Williams R. The Wilson’s disease gene and phenotypic diversity. J Hepatol. 2001;34:165–71.PubMedGoogle Scholar
  33. 33.
    Mehta R, Templeton D, O’Brien PJ. Mitochondrial involvement in genetically determined transition metal toxicity. II. Copper toxicity. Chem Biol Interact. 2006;163:77–85.PubMedGoogle Scholar
  34. 34.
    Roberts EA, Schilsky ML. A practice guideline on Wilson disease. Hepatology. 2003;37:1475–92.PubMedGoogle Scholar
  35. 35.
    Ala A, Walker AP, Ashkan K, et al. Wilson’s disease. Lancet. 2007;369:397–408.PubMedGoogle Scholar
  36. 36.
    Roberts EA, Schilky ML. Diagnosis and treatment of Wilson disease: an update. Hepatology. 2008;47:2089–111.PubMedGoogle Scholar
  37. 37.
    Ferenci P, Caca K, Loudianos G, et al. Diagnosis and phenotypic classification of Wilson disease. Liver Int. 2003;23:139–42.PubMedGoogle Scholar
  38. 38.
    Nicastro E, Ranucci G, Vajro P, et al. Re-evaluation of the diagnostic criteria for Wilson disease in children with mild liver disease. Hepatology. 2010;52:1948–56.PubMedGoogle Scholar
  39. 39.
    Hayashi H, Tatsumi Y, Yahata S, et al. Acute hepatic phenotype of Wilson’s disease: clinical features of acute episodes and chronic lesions remaining in survivors. J Clin Transl Hepatol. 2015;3:239–45.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Walshe JM. Diagnosis and treatment of presymptomatic Wilson’s disease. Lancet. 1988;2:435–7.PubMedGoogle Scholar
  41. 41.
    Scheinberg IH, Sternlieb I. Wilson’s disease. In: Smith Jr LH, editor. Major problems in internal medicine, vol. 23. Philadelphia, PA: WB Saunders; 1984. p. 25–35.Google Scholar
  42. 42.
    Strohmeyer FW, Ishak KG. Histology of the liver in Wilson’s disease: a study of 34 cases. Am J Clin Pathol. 1980;73:12–24.Google Scholar
  43. 43.
    Sternlieb I. Evolution of the hepatic lesion in Wilson’s disease (hepatolenticular degeneration). Prog Liver Dis. 1972;4:511–25.PubMedGoogle Scholar
  44. 44.
    Strand S, Hofmann WJ, Grambihler A, et al. Hepatic failure and liver cell damage in acute Wilson’s disease involve CD95 (APO-1/Fas) mediated apoptosis. Nat Med. 1998;4:588–93.PubMedGoogle Scholar
  45. 45.
    Korman JD, Volenberg I, Balko J, et al. Pediatric and adult acute liver failure study groups. Screening for Wilson disease in acute liver failure: a comparison of currently available diagnostic tests. Hepatology. 2008;48:1167–74.PubMedPubMedCentralGoogle Scholar
  46. 46.
    Ala A, Walker AP, Ashkan K, Dooley JS, Schilsky ML. Wilson’s disease. Lancet. 2007;369:397–408.PubMedGoogle Scholar
  47. 47.
    Davis W, Chowrimootoo GF, Seymour CA. Defective biliary copper excretion in Wilson’s disease: the role of caeruloplasmin. Eur J Clin Investig. 1996;26:893–901.Google Scholar
  48. 48.
    Walshe JM. Treatment of Wilson’s disease with trientine (triethylene tetramine) dihydrochloride. Lancet. 1982;1:643–7.PubMedGoogle Scholar
  49. 49.
    Dhawan A, Taylor RM, Cheeseman P, et al. Wilson’s disease in children: 37-year experience and revised King’s score for liver transplantation. Liver Transplant. 2005;11:441–8.Google Scholar
  50. 50.
    Bellary SV, Hassanein T, van Thiel DH. Liver transplantation for Wilson’s disease. J Hepatol. 1995;23:373–81.PubMedGoogle Scholar
  51. 51.
    Rakela J, Kurtz SB, McCarthy JT, Ludwig J, Ascher NL, Bloomer JR, et al. Fulminant Wilson’s disease treated with postdilution hemofiltration and orthotopic liver transplantation. Gastroenterology. 1986;90:2004–7.PubMedGoogle Scholar
  52. 52.
    Pankit AN, Bhave SA. Copper metabolic defects and liver disease: environmental aspect. J Gastroenterol Hepatol. 2002;17(Supp. 3):S403–7.PubMedGoogle Scholar
  53. 53.
    Adamson M, Reiner B, Olson JL, et al. Indian child cirrhosis in an American child. Gastroenterology. 1992;102:1771–7.PubMedGoogle Scholar
  54. 54.
    Joshi VV. Indian child cirrhosis. Perspect Pediatr Pathol. 1987;11:175–92.PubMedGoogle Scholar
  55. 55.
    Muller T, Langner C, Fuchsbichler A, et al. Immunohistochemical analysis of Mallory bodies in Wilsonian and non-Wilsonian hepatic copper toxicosis. Hepatology. 2004;39:963–9.PubMedGoogle Scholar
  56. 56.
    Bawdekar AR, Bhave SA, Pradham AM, et al. Long-term survival in Indian childhood cirrhosis treated with D-penicillamine. Arch Dis Child. 1996;74:32–5.Google Scholar
  57. 57.
    Muller T, Feichtinger H, Berger H, Muller W. Endemic Tyrolean infantile cirrhosis: an ecogenic disorder. Lancet. 1996;347:877–80.PubMedGoogle Scholar
  58. 58.
    Muller-Hocker J, Summer KH, Schramel P, Rodeck B. Different pathomorphologic patterns in exogenic infantile copper intoxication of the liver. Pathol Res Pract 1998; 194: HAHN MD.Google Scholar
  59. 59.
    Hayashi H, Shinohara T, Goto K, et al. Liver structures of a patient with idiopathic copper toxicosis. Med Mol Morphol. 2012;45:105–9.PubMedGoogle Scholar
  60. 60.
    Petris M, Mercer JFB, Culvenor JG, et al. Ligand-regulated transport of the Menkes copper P-type ATPase from the Golgi apparatus to the plasma membrane; a novel mechanism of regulated trafficking. ENBO J. 1996;15:6084–95.Google Scholar
  61. 61.
    Montgomery BD, Anderson KE, Bonkovsky HL. Porphyrias. N Engl J Med. 2017;377(9):862–72.Google Scholar
  62. 62.
    Anderson KE, Bloomer JR, Bonkovsky HL, et al. Recommendations for the diagnosis and treatment of the acute por-phyrias. Ann Intern Med. 2005;142:439–50.PubMedGoogle Scholar
  63. 63.
    Whatley SD, Badminton MN. Acute intermittent porphyria. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews. Seattle: University of Washington; 2013.Google Scholar
  64. 64.
    Bissell DM, Lai JC, Meister RK, Blanc PD. Role of delta-aminolevulinic acid in the symptoms of acute porphyria. Am J Med. 2015;128:311–7.Google Scholar
  65. 65.
    Pischik E, Kauppinen R. An update of clinical management of acute intermittent porphyria. Appl Clin Genet. 2015;8:201–14.PubMedPubMedCentralGoogle Scholar
  66. 66.
    Kappas A, Sassa S, Galbraith RA, Nordman Y. The porphyrias. In: Scriver CR, Beaaudet A, Sly WS, Valle D, editors. The metabolic basis of inherited disease. New York: McGraw-Hill; 1989. p. 1305–65.Google Scholar
  67. 67.
    Okano J, Horie Y, Kawasaki H, Kondo M. Interferon treatment of porphyria cutanea associated with chronic hepatitis C. Hepato-Gastroenterol. 1997;44:525–8.Google Scholar
  68. 68.
    Kondo M, Horie Y, Okano J, et al. High prevalence of hepatitis C virus infection in Japanese patients with porphyria cutanea tarda. Hepatology. 1997;26:246.PubMedGoogle Scholar
  69. 69.
    Ashwani K, Singal AK, Parker C, Bowden C, Thapar M, Liu L, McGuire BM. Liver transplantation in the Management of Porphyria. Hepatology. 2014;60:1082–9.Google Scholar
  70. 70.
    Kyle RA, Gertz MA. Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin Hematol. 1995;32:45–59.PubMedGoogle Scholar
  71. 71.
    Gertz MA, Kyle RA. Hepatic amyloidosis (primary [AL], immunoglobulin light chain): the natural history in 80 patients. Am J Med. 1988;85:73–80.PubMedGoogle Scholar
  72. 72.
    Kyle RA, Greipp PR. Amyloidosis (AL). Clinical and laboratory features in 229 cases. Mayo Clin Proc. 1983;58:665–83.PubMedGoogle Scholar
  73. 73.
    Levy M, Fryd CH, Eliakim M. Intrahepatic obstructive jaundice due to amyloidosis of the liver. A case report and review of the literature. Gastroenterology. 1971;61:234–8.PubMedGoogle Scholar
  74. 74.
    Peters RA, Koukoulis G, Gimson A, Portman B, Westaby D, Williams R. Primary amyloidosis and severe intrahepatic cholestatic jaundice. Gut. 1994;35:1322–5.PubMedPubMedCentralGoogle Scholar
  75. 75.
    Yamamoto T, Maeda N, Kawasaki H. Hepatic failure in a case of multiple myeloma-associated amyloidosis (kappa-AL). J Gastroenterol. 1995;30:393–7.PubMedGoogle Scholar
  76. 76.
    Dohmen K, Nagano M, Iwakiri M, Yamano Y, Kikuchi Y, Mizoguchi M, et al. A case of prominent hepatic cholestasis developing to hepatic failure in lambda-AL amyloidosis. Gastroenterol Jpn. 1991;26:376–81.PubMedGoogle Scholar
  77. 77.
    Zeijen RNM, Sels JPJE, Flendrig JA, Arends JW. Portal hypertension and intrahepatic cholestasis in hepatic amyloidosis. Netherland J Med. 1991;38:257–61.Google Scholar
  78. 78.
    Hormans Y, Brenard R, Ferrant A, Lagneaux G, Geubel AP. Long-term favorable outcome of portal hypertension complicating primary systemic amyloidosis. Liver. 1995;15:332–4.Google Scholar
  79. 79.
    Melato M, Manconi R, Magris D, Morassi P, Benussi DG, Tiribelli C. Different morphologic aspects and clinical features in massive hepatic amyloidosis. Digestion. 1984;29:138–45.PubMedGoogle Scholar
  80. 80.
    Mergo PJ, Ros PR, Buetow PC, Buck JL. Diffuse disease of the liver: radiologic-pathologic correlation. Radiographics. 1994;14:1291–307.PubMedGoogle Scholar
  81. 81.
    Itescu S. Hepatic amyloidosis. An unusual cause of ascites and portal hypertension. Arch Intern Med. 1984;144:2257–9.PubMedGoogle Scholar
  82. 82.
    Beck K, Dischler W, Helms M, Kiani B, Sickinger K, Tenner R. Atlas der Laparoskopie. F.K. Schattauer-Verlag: Stuttgart and New York; 1968.Google Scholar
  83. 83.
    Stauffer MH, Gross JB, Foulk WT, Dahlin DC. Amyloidosis: diagnosis with needle biopsy of the liver in eighteen patients. Gastroenterology. 1961;41:92–6.Google Scholar
  84. 84.
    Iwata T, Hoshii Y, Kawano H, Gondo T, Takahashi M, Ishihara T, et al. Hepatic amyloidosis in Japan: histological and morphometric analysis based on amyloid proteins. Hum Pathol. 1995;26:1148–53.PubMedGoogle Scholar
  85. 85.
    Skinner MS, Kattine AA, Spurlock BO. Electron microscope: Pico observations of early amyloidosis in human liver. Gastroenterology. 1966;50:243–7.Google Scholar
  86. 86.
    Livni N, Behar AJ, Lafair JS. Unusual amyloid bodies in human liver. Ultrastructural and freeze-etching studies. Isr J Med Sci. 1977;13:1163–70.PubMedGoogle Scholar
  87. 87.
    Finkelstein SD, Fornasier VL, Pruzanski W. Intrahepatic cholestasis with predominant pericentral deposition in systemic amyloidosis. Hum Pathol. 1981;12:470–2.PubMedGoogle Scholar
  88. 88.
    Mir-Madjlessi SH, Farmer RG, Hawk WA Jr. Cholestatic jaundice associated with primary amyloidosis. Cleve Clin Q. 1972;39:167–75.PubMedGoogle Scholar
  89. 89.
    Tsukada N, Ackerley CA, Phillips MJ. The structure and organization of bile canalicular cytoskeleton with special reference to actin and actin-binding proteins. Hepatology. 1995;21:1106–13.PubMedGoogle Scholar
  90. 90.
    Terada T, Hirata K, Hisada Y, Hoshii Y, Nakanuma Y. Obstructive jaundice caused by the deposition of amyloid-like substances in the extrahepatic and large intrahepatic bile ducts in a patient with multiple myeloma. Histopathology. 1994;24:485–7.PubMedGoogle Scholar
  91. 91.
    Kyle RA, Gerz MA, Greipp PR, et al. A trial of three regimens for primary amyloidosis: colchicine alone, melphalan, prednisone, and colchicine. N Engl J Med. 1997;336:1202–7.PubMedGoogle Scholar
  92. 92.
    Palladini G, Milani P, Foli A, et al. Oral melphalan and dexamethasone grants extended survival with minimal toxicity in AL amyloidosis: long term results of a risk-adapted approach. Hema. 2014;99:743–50.Google Scholar
  93. 93.
    Morie AG. Immunoglobulin light chain amyloidosis: 214 up-date on diagnosis, prognosis, and treatment. Am J Hematol. 2014;89:1133–40.Google Scholar
  94. 94.
    Gertz MA, Landau H, Comenzo RL, et al. First-in-human phase I/II study of NEOD001 in patients with light chain amyloidosis and persistent organ dysfunction. J Clin Oncol. 2016;34:1097–103.PubMedPubMedCentralGoogle Scholar
  95. 95.
    Rosen E, Bakshi N, Watters A, Rosen HR, Mehler PS. Hepatic complications of anorexia nervosa. Dis Dis Sci. 2017;62:2977–81.Google Scholar
  96. 96.
    Rautou PE, Cazals-Hatem D, Moreau R, Francoz C, Feldmann G, Lebrec D, Ogier-Denis E, Bedossa P, Valla D, Durand F. Acute liver cell damage in patients with anorexia nervosa: a possible role of starvation-induced hepatocyte autophagy. Gastroenterology. 2008;135:840–8.PubMedGoogle Scholar
  97. 97.
    Komuta M, Harada M, Ueno T, Uchimura Y, Inada C, Mitsuyama K, Sakisaka S, Sata M, Tanakawa K. Unusual accumulation of glycogen in liver parenchymal cells in a patient with anorexia nervosa. Int Med. 1998;37:678–82.Google Scholar
  98. 98.
    Bridet L, Martin JJ, Nuno JL. Acute liver damage and anorexia nervosa: a case report. Turk J Gastroenterol. 2014;25:205–8.PubMedGoogle Scholar
  99. 99.
    von Gierke E. Liver and kidney in glycogen storage disease. Beitr Pathol Anat. 1929;82:497–513.Google Scholar
  100. 100.
    Labrune P, Trioche P, Duvaltier I, Chevalier P, Odièvre M. Hepatocellular adenomas in glycogen storage disease type I and III: a series of 43 patients and review of the literature. J Pediatr Gastroenterol Nutr. 1997;24:276–9.PubMedGoogle Scholar
  101. 101.
    Coire CI, Qizilbash AH, Castelli MF. Hepatic adenomata in type Ia glycogen storage disease. Arch Pathol Lab Med. 1987;111:166–9.PubMedGoogle Scholar
  102. 102.
    Limmer J, Fleig WE, Leupold D, Bittner R, Ditschuneit H, Beger HG. Hepatocellular carcinoma in type I glycogen storage disease. Hepatology. 1988;8:531–7.PubMedGoogle Scholar
  103. 103.
    Panaro F, Andorno E, Basile G, et al. Simultaneous liver-kidney transplantation for glycogen storage disease type 1A (von Girke’s disease). Tranplant Proc. 2004;36:1483–4.Google Scholar
  104. 104.
    Parmieri L, Pardo B, Lasorsa FM, del Arco A, Kobayashi K, Iijima M, Runswick MJ, Walker JE, Saheki T, Satrustegui J, Palmieri F. Citrin and aralar1 are Ca2+−stimulated aspartate/glutamate transporters in mitochondria. EMBO J. 2001;20:5060–9.Google Scholar
  105. 105.
    Kobayashi K, Sinasac DS, Iijima M, Boright AP, Begum L, Lee JR, et al. The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein. Nat Genet. 1999;22:159–63.PubMedGoogle Scholar
  106. 106.
    Kobayashi K, Saheki T. Aspartate glutamate carrier (Citrin) deficiency. In: Brorer S, Wagner CA, editors. Membrane transporter diseases. New York, NY: Kluwer Academic/Plenum Publishers; 2003. p. 147–60.Google Scholar
  107. 107.
    Saheki T, Kobayashi K. Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset type IIcitrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD). J Hum Genet. 2002;47:333–41.PubMedGoogle Scholar
  108. 108.
    Saheki T, Kobayashi K, Iijima M, Horiuchi M, Begum L, Jalil MA, et al. Adult-onset type II citrullinemia and idiopathic neonatal hepatitis caused by citrin deficiency: involvement of the aspartate glutamate carrier for urea synthesis and maintenance of the urea cycle. Mol Genet Metab. 2004;81(Suppl 1):S20–6.PubMedGoogle Scholar
  109. 109.
    Takagi H, Hagiwara S, Hashizume H, Kanda D, Sato K, Sohara N, et al. Adult onset type II citrullinemia as a cause of non-alcoholic steatohepatitis. J Hepatol. 2006;44:236–9.PubMedGoogle Scholar
  110. 110.
    Nakamura M, Yazaki M, Kobayashi Y, Fukushima K, Ikeda S, Kobayashi K, Saheki T, Nakaya Y. The characteristics of food intake in patients with type II citrullinemia. J Nutr Sci Vitaminol. 2011;57:239–45.PubMedGoogle Scholar
  111. 111.
    Todo S, Starzl TE, Tzakis A, Benkov KJ, Kalousek F, Saheki T, et al. Orthotopic liver transplantation for urea cycle enzyme deficiency. Hepatology. 1992;15:419–22.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Masaki Iwai
    • 1
    Email author
  • Atsushi Kitamura
    • 2
  • Hajime Isomoto
    • 3
  • Yutaka Horie
    • 2
  • Wilson M. S. Tsui
    • 4
  1. 1.KyotoJapan
  2. 2.ShimaneJapan
  3. 3.TottoriJapan
  4. 4.Hong KongChina

Personalised recommendations