Metabolic Diseases

  • Enid Gilbert-Barness
  • Diane E. Spicer
  • Thora S. Steffensen


Galactosemia is an autosomal-recessive disorder with a frequency of 1 in 60,000 live births. The classic form of galactosemia is attributable to a deficiency of galactose-1-phosphate uridyltransferase, which results in the accumulation of galactose, galactose-1-phosphate, and galactitol in the tissues. Less frequently, galactosemia may be attributable to galactokinase or galactose epimerase deficiency. If the newborn infant is fed lactose, vomiting, diarrhea, hyperbilirubinemia, hepatosplenomegaly, renal tubular dysfunction, liver failure, and cataracts develop. Galactose is present in the blood of affected newborns. Diagnosis is confirmed by the assay of red blood cell galactose-1-phosphate uridyltransferase, which is reliable unless the infant has received red blood cell transfusions. The pathologic changes are pronounced steatosis of hepatocytes, with a progressive pseudoacinar change of hepatic architecture, bile duct proliferation, cholestasis, focal necrosis, and finally cirrhosis. Other features are pancreatic islet cell hyperplasia and vacuolization of renal tubular epithelial cells. At autopsy the brain is edematous, and gliosis and neuronal necrosis have been attributed to hypoxic-ischemic damage. The pathologic changes of hereditary fructose intolerance and tyrosinemia are similar.


Fabry Disease Wilson Disease Neuronal Ceroid Lipofuscinosis Carnitine Deficiency Zellweger Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Alroy J, Ucci AA. Skin biopsy: a useful tool in the diagnosis of lysosomal storage diseases. Ultrastruct Pathol. 2006;30:489–503.CrossRefPubMedGoogle Scholar
  2. Andrews NC. Disorders of iron metabolism. N Engl J Med. 1999;341:1986–95.CrossRefPubMedGoogle Scholar
  3. Babovic-Vuksanovic D et al. Severe hypoglycemia as a presenting symptom of carbohydrate-deficient glycoprotein syndrome. J Pediatr. 1999;135:775–81.CrossRefPubMedGoogle Scholar
  4. Barness L, Gilbert-Barness E. Metabolic diseases. In: Gilbert-Barness E, editor. Potter’s pathology of the fetus and infant. 2nd ed. Philadelphia: Mosby Year book; 1997a.Google Scholar
  5. Barness L, Gilbert-Barness E. Metabolic disorders. In: Gilbert-Barness E, editor. Atlas of developmental and infant pathology. Philadelphia: Mosby Year Book; 1997b.Google Scholar
  6. Bioulac-Sage P et al. Fatal neonatal liver failure and mitochondrial cytopathy (oxidative phosphorylation deficiency): a light and electron microscopic study of the liver. Hepatology. 1993;18:839–46.CrossRefPubMedGoogle Scholar
  7. Boles RG et al. Retrospective biochemical screening of fatty acid oxidation disorders in post-mortem livers of 418 cases of sudden death in the first year of life. J Pediatr. 1998;132:924–33.CrossRefPubMedGoogle Scholar
  8. Bove KE et al. Bile acid synthetic defects and liver disease. Pediatr Dev Pathol. 2000;3:1–16.CrossRefPubMedGoogle Scholar
  9. Carstea ED et al. Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis. Science. 1997;277:228–31.CrossRefPubMedGoogle Scholar
  10. Chang Y et al. Inherited syndrome of infantile oligoponto-cerebellar atrophy, micronodular cirrhosis, and renal tubular microcysts: review of the literature and a report of an additional case. Acta Neuropathol. 1993;86:399–404.CrossRefPubMedGoogle Scholar
  11. Dahl HHM, Thorburn DR. Seminars in medical genetics—mitochondrial diseases. Am J Med Genet. 2001;106:1–114.CrossRefPubMedGoogle Scholar
  12. DeLonlay P et al. Hyperinsulinemic hypoglycemia as a presenting sign in phosphomannose isomerase deficiency: a new manifestation of carbohydrate-deficient glycoprotein syndrome treatable with mannose. J Pediatr. 1999;135:379–83.CrossRefGoogle Scholar
  13. Dimmick JE, Vallance HD. Inborn errors of metabolism. In: Stocker JT, Dehner LP, editors. Pediatric pathology. 2nd ed. New York: Lippincott Williams, and Wilkins; 2001.Google Scholar
  14. Fox BT et al. Gene repair using chimeric RNA/DNA oligonucleotides. Semin Liver Dis. 1999;19:93–104.CrossRefGoogle Scholar
  15. Freeze HH, Aebi M. Molecular basis of carbohydrate-deficient glycoprotein syndromes type 1 with normal phosphomannomutase activity. Biochim Biophys Acta. 1999;1455:167–78.CrossRefPubMedGoogle Scholar
  16. Gilbert-Barness E, Barness L. Metabolic diseases: foundations of clinical management, genetics, and pathology. Natick: Eaton Publishing; 2000.Google Scholar
  17. Gilbert-Barness E, editor. Potter’s pathology of the fetus, infant and child. 2nd ed. Philadelphia: Elsevier; 2007.Google Scholar
  18. Holme E et al. Tyrosinemia type 1 and NTBC. J Inherit Metab Dis. 1998;21:507–17.CrossRefPubMedGoogle Scholar
  19. Ibdah JA et al. A fetal fatty-acid oxidation disorder as a cause of liver disease in pregnant women. N Engl J Med. 1999;340:1723–31.CrossRefPubMedGoogle Scholar
  20. Jaffe R. Liver transplant pathology in pediatric metabolic disorders. Perspect Pediatr Pathol. 1999;21:24–39.Google Scholar
  21. Jevon GP, Dimmick JE. Histopathologic approach to metabolic liver disease. Parts I and II. Perspect Pediatr Pathol. 1999;21:40–69.Google Scholar
  22. Jevon GP, Finegold X. Reliability of histological criteria in glycogen storage disease of the liver. Pediatr Pathol. 1994;14:709.CrossRefPubMedGoogle Scholar
  23. Kay MA et al. Hepatic gene-therapy: persistent expression of human alpha-1 -antitrypsin in dogs after autologous transplantation of retro-viral transduced hepatocytes. PNAS. 1992;89:89–92.CrossRefPubMedPubMedCentralGoogle Scholar
  24. Kemp PM et al. Whole blood levels of dodecanoic acid, a routinely detectable forensic marker for a genetic disease often misdiagnosed as sudden infant death syndrome (SIDS): MCAD deficiency. Am J Forensic Med Pathol. 1996;17:79–92.CrossRefPubMedGoogle Scholar
  25. Labelle Y et al. Characterization of the human fumaryl-acetoacetate hydrolase gene and identification of a missense mutation abolishing enzyme activity. Hum Mol Genet. 1993;2:941–6.CrossRefPubMedGoogle Scholar
  26. Lindstedt S et al. Treatment of hereditary tyrosinemia type I by inhibition of 4-hydroxy phenyl pyruvatedioxygenase. Lancet. 1992;340:813–7.CrossRefPubMedGoogle Scholar
  27. Morris AAM et al. Liver failure associated with mitochondrial DNA depletion. J Hepatol. 1998;28:556–63.CrossRefPubMedGoogle Scholar
  28. Pan X, Kelly S, Melin-Aldana H, Malladi P, Whitington PF. Novel mechanism of fetal hepatocyte injury in congenital alloimmune hepatitis involves the terminal complement cascade. Hepatology. 2010;51:2061–8.CrossRefPubMedGoogle Scholar
  29. Rinaldo P et al. Clinical and biochemical features of fatty acid oxidation disorders. Curr Opin Pediatr. 1998;10:615–21.CrossRefPubMedGoogle Scholar
  30. Ros J et al. NTBC as palliative treatment in chronic tyrosinemia type I. J Inherit Metab Dis. 1999;22:665–6.CrossRefPubMedGoogle Scholar
  31. Ruchelli ED et al. Severe perinatal liver disease and Down syndrome: an apparent relationship. Hum Pathol. 1991;22:1274–80.CrossRefPubMedGoogle Scholar
  32. Schwab M et al. Down syndrome, transient myeloproliferative disorder in infantile liver fibrosis. Med Pediatr Oncol. 1998;31:159–65.CrossRefPubMedGoogle Scholar
  33. Shneider BL. Genetic cholestasis syndromes. J Pediatr Gastroenterol Nutr. 1999;28:124–31.CrossRefPubMedGoogle Scholar
  34. Silver MM et al. Hepatic morphology and iron quantitation in perinatal hemochromatosis. Am J Pathol. 1993;143:1312–25.PubMedPubMedCentralGoogle Scholar
  35. Stocker JT, Dehner LP, Husain AN, editors. Stocker and Dehner’s pediatric pathology. 3rd ed. Philadelphia: Lippincott Williams, & Wilkins; 2011.Google Scholar
  36. Tavill AS. Clinical implications of the hemochromatosis gene. N Engl J Med. 1999;341:755–7.CrossRefPubMedGoogle Scholar
  37. Wilson JM. Ex vivo gene therapy of familial hypercholesterolemia. Hum Gene Ther. 1992;3:179–222.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Enid Gilbert-Barness
    • 1
  • Diane E. Spicer
    • 2
  • Thora S. Steffensen
    • 3
  1. 1.Laboratory Medicine, Pediatrics and Obstetrics and Gynecology Tampa General Hospital Morsani College of MedicineUniversity of South FloridaTampaUSA
  2. 2.Department of Pediatrics-CardiologyUniversity of FloridaValricoUSA
  3. 3.Department of PathologyTampa General HospitalTampaUSA

Personalised recommendations