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Constitutional Nonhemolytic Hyperbilirubinemia with Findings Resembling Kernicterus

Constitutional Nonhemolytic Hyperbilirubinemia with Findings Resembling Kernicterus Abstract One of the most striking effects of liver diseases upon the central nervous system is the characteristic brain damage (kernicterus) which may occur in infants suffering from severe neonatal jaundice. Although the morphologic features of kernicterus have been known for half a century, there is still no completely satisfactory explanation as to the pathogenesis of the brain lesions. Numerous hypotheses have been advanced stressing the relevance of such diverse factors as anoxia, anemia, antigen-antibody reaction, infection, intoxication, and liver failure. In the attempt to contribute to the clarification of this problem, the clinical and pathologic features of an apparently unique case will be presented. The patient, a 44-year-old woman, was affected by constitutional nonhemolytic hyperbilirubinemia, associated since early infancy with an "extrapyramidal" symptom complex. Post mortem, lesions of the brain were found which are consistent with the pathologic diagnosis of sequelae of kernicterus. The main feature of this case will References 1. Dubin, I. N., and Johnson, F. B.: Chronic Idiopathic Jaundice with Unidentified Pigment in Liver Cells: A New Clinico-Pathologic Entity with a Report of 12 Cases , Medicine 33:155, 1954.Crossref 2. Dutton, G. J., and Storey, I. D. E.: Uridine Components in Glucuronic Acid Metabolism: Formation of Glucuronides in Liver Suspensions , Biochem. J. 57:275, 1954. 3. Arias, I. M., and London, I. M.: Bilirubin Glucuronide Formation in Vitro: Demonstration of a Defect in Gilbert's Disease , Science 126:563, 1957.Crossref 4. Gilbert, A., and Léreboullet: La cholémie simple familiale , Gaz. hebd. méd. 49:889, 1902. 5. Dameshek, W., and Singer, K.: Familial Nonhemolytic Jaundice: Constitutional Hepatic Dysfunction with Indirect van den Bergh Reaction , Arch. Int. Med. 67:259, 1941.Crossref 6. Alwall, N.: On Hereditary, Non-Hemolytic Bilirubinemia , Acta med. scandinav. 123:560, 1946.Crossref 7. Comfort, M. W.: Constitutional Hepatic Dysfunction , M. Clin. North America 29:982, 1945. 8. Meulengracht, E.: Review of Chronic Intermittent Juvenile Jaundice , Quart. J. Med. 16:83, 1947. 9. Blanton, W. B., and Blanton, F. M.: Constitutional Hepatic Dysfunction—Familial Nonhemolytic Jaundice , Ann. Int. Med. 43:598, 1955.Crossref 10. Baroody, W. G., and Shugart, R. T.: Familial Non-Hemolytic Icterus , Am. J. Med. 20:314, 1956.Crossref 11. Schmid, R.: Direct-Reacting Bilirubin, Bilirubin Glucuronide, in Serum, Bile and Urine , Science 124:76, 1956.Crossref 12. Billing, B. H., and Lathe, G. H.: Excretion of Bilirubin as an Ester Glucuronide, Giving the Direct van den Bergh Reaction , Biochem. J. 63:6P, 1956. 13. Levvy, G. A.: Glucuronide Metabolism, with Special Reference to the Steroid Hormones , in Vitamins and Hormones: Advances and Applications , edited by R. S. Harris and K. V. Thimann, New York, Academic Press, Inc., 1956, Vol. 14, p. 267. 14. Spiller, W. G.: Severe Jaundice in the Newborn Child: A Cause of Spastic Cerebral Diplegia , Am. J. M. Sc. 149:345, 1915.Crossref 15. Ford, F. R.: Diseases of the Nervous System in Infancy, Childhood and Adolescence , Ed. 2, Springfield, Ill., Charles C Thomas, Publisher, 1944. 16. Yannet, H., and Lieberman, R.: Central Nervous System Complications Associated with Kernicterus , J. A. M. A. 130:335, 1946.Crossref 17. Lande, L.: Clinical Signs and Development of Survivors of Kernicterus Due to Rh Sensitization , J. Pediat. 32:693, 1948.Crossref 18. Pentschew, A.: Encephalopathia posticterica infantum , Arch. Psychiat. 118-180:118, 1948.Crossref 19. Evans, P. R., and Polani, P. E.: The Neurological Sequelae of Rh Sensitization , Quart. J. Med. 19:129, 1950. 20. Gerrard, J.: Kernicterus , Brain 75:526, 1952.Crossref 21. Perlstein, M.: Neurologic Sequelae of Erythroblastosis Fetalis , Am. J. Dis. Child. 79:605, 1950. 22. Crigler, J. F., Jr., and Najjar, V. A.: Congenital Familial Nonhemolytic Jaundice with Kernicterus , Pediatrics 10:169, 1952. 23. Childs, B., and Najjar, V. A.: Familial Non-Hemolytic Jaundice with Kernicterus , Pediatrics 18:369, 1956. 24. Rosenthal, I. M.; Zimmerman, H. J., and Hardy, N.: Congenital Nonhemolytic Jaundice with Disease of the Central Nervous System , Pediatrics 18:378, 1956. 25. Zimmerman, H. M., and Yannet, E.: Kernicterus: Jaundice of the Nuclear Masses of the Brain , Am. J. Dis. Child. 45:740, 1933.Crossref 26. Forster, F. M., and McCormack, R. A.: Kernicterus Unassociated with Erythroblastosis Fetalis , J. Neuropath. & Exper. Neurol. 3:379, 1944. 27. Bertrand, I.: Lésions du système nerveux central dans deux cas d'ictère nucléaire du nouvau-né , Rev. hémat. 1:399, 1946. 28. Jacob, H.: Über die Hirnschäden bei Icterus neonatorum gravis (Kernikterus) , Arch. Psychiat. 118-180:1, 1948. 29. Becker, P. F. L., and Vogel, P.: Kernicterus: A Review, with Report of 7 Cases , J. Neuropath. & Exper. Neurol. 7:190, 1948. 30. Dereymaeker, A.: Contribution à l'étude clinique, anatomique et expériméntale de l'ictère nucléaire du nouveau-né , Paris, Masson & Cie, 1949. 31. Claireaux, A.: Haemolytic Disease of the Newborn: A Clinical-Pathological Study of 157 Cases; Nuclear Jaundice (Kernicterus) , Arch. Dis. Childhood 25:61, 1950. 32. Zimmerman, H. M., and Yannet, H.: Cerebral Sequelae of Icterus Gravis Neonatorum and Their Relation to Kernikterus , Am. J. Dis. Child. 49:418, 1935. 33. Biemond, A., and van Creveld, S.: Nuclear Jaundice in Neonatal Sepsis with Jaundice , Arch. Dis. Childhood 12:173, 1937. 34. van Westrienen, A., and de Lange, C.: Atropinbehandlung bei den Folgen von Kernickterus , Jahrb. Kinderh. 150:257, 1937. 35. Fitzgerald, G. M.; Greenfield, J. G., and Kounine, B.: Neurological Sequelae of "Kernicterus," Brain 62:292, 1939. 36. Sobel, I. P., and Zucker, J. M.: Icterus Gravis Neonatorum: End Results of the Syndrome of Nuclear Jaundice , J. Pediat. 16:445, 1940. 37. van Bogaert, L.: Aspect histologique d'une séquelle tardive de l'ictère nucléaire , Ann. pædiat. 168:57, 1947. 38. Dechamps, A., and van Bogaert, L.: Idiotie, épilepsie choréoathétose double avec une syndrome médullaire, séquelles tardives de l'ictère nucléaire , Acta neurol. et psychiat. belg. 48:480, 1948. 39. Mann, L. B., Jr., and Courville, C. B.: Neurological Manifestations of Jaundice in the Newborn, with Particular Reference to the Chronic Residuals , Bull. Los Angeles Neurol. Soc. 13:69, 1948. 40. McLardy, T.: Projection of the Centromedian Nucleus of the Human Thalamus , Brain 71:290, 1948. 41. Crome, L.: Morphological Nervous Changes in Survivors of Severe Jaundice of the Newborn , J. Neurol. Neurosurg. & Psychiat. 18:17, 1955. 42. Meriwether, L. S.; Hager, H., and Scholz, W.: Kernicterus: Hypoxemia, Significant Pathogenic Factor , A. M. A. Arch. Neurol. & Psychiat. 73:293, 1955. 43. Soeken, G.: Zur Problematik der Hirnveränderungen bei Morbus hæmolyticus neonatorum , J. Hirnforsch. 2:335, 1956. 44. Brown, A. K., and Zuelzer, W. W.: Studies in Hyperbilirubinemia: I. Hyperbilirubinemia of the Newborn Unrelated to Isoimmunization , A. M. A. J. Dis. Child. 93:263, 1957.Crossref 45. Meyer, T. C.: A Study of Serum Bilirubin Levels in Relation to Kernicterus and Prematurity , Arch. Dis. Childhood 31:75, 1956.Crossref 46. Parsons, L.: The Clinician and the Rh Factor , Lancet 1:815, 1947.Crossref 47. Govan, A. D. T., and Scott, J. M.: Kernicterus and Prematurity , Lancet 1:611, 1953.Crossref 48. Pichler, M. M.: Hemolytic Disease of the Newborn , London, Oxford University Press, 1949. 49. Claireaux, A. E.; Cole, P. G., and Lathe, G. H.: Icterus of Brain in the Newborn , Lancet 2:1226, 1953.Crossref 50. Zuelzer, W. W., and Mudgett, R. T.: Kernicterus: Etiologic Study Based on an Analysis of 55 Cases , Pediatrics 6:452, 1950. 51. Hsia, D. Y.; Allen, F. H., Jr.; Gellis, S. S., and Diamond, L. K.: Erythroblastosis Fetalis: VIII. Studies of Serum Bilirubin in Relation to Kernicterus , New England J. Med. 247:668, 1952.Crossref 52. Küster, F., and Krings, H.: Die Bedeutung des Bilirubins für die Pathogenese der Hirnschadens bei der Erythroblastosis fetalis , Ztschr. Kinderh. 67:503, 1950.Crossref 53. Waters, W. J., and Britton, H. A.: Bilirubin Encephalopathy: Preliminary Studies Related to Production , Pediatrics 15:45, 1955. 54. Malloy, H. T., and Lowenstein, L.: Hereditary Jaundice in the Rat , Canad. M. A. J. 42:122, 1940. 55. Carbone, J. V., and Grodsky, G. M.: Constitutional Nonhemolytic Hyperbilirubinemia in the Rat: Defect of Bilirubin Conjugation , Proc. Soc. Exper. Biol. & Med. 94:461, 1957. 56. Lathe, G. H., and Walker, M.: An Enzyme Defect in Human Neonatal Jaundice, and in Gunn's Strain of Jaundiced Rats , Biochem. J. 67:9P, 1957. 57. Day, R. L.: Inhibition of Brain Respiration in Vitro by Bilirubin: Reversal of Inhibition by Various Means , Proc. Soc. Exper. Biol. & Med. 85:261, 1954. 58. Ernster, L.; Herlin, L., and Zetterström, R.: Experimental Studies on the Pathogenesis of Kernicterus , Pediatrics 20:6471957. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png A.M.A. Archives of Neurology & Psychiatry American Medical Association

Constitutional Nonhemolytic Hyperbilirubinemia with Findings Resembling Kernicterus

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American Medical Association
Copyright
Copyright © 1959 American Medical Association. All Rights Reserved.
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0096-6886
DOI
10.1001/archneurpsyc.1959.02340130075008
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Abstract

Abstract One of the most striking effects of liver diseases upon the central nervous system is the characteristic brain damage (kernicterus) which may occur in infants suffering from severe neonatal jaundice. Although the morphologic features of kernicterus have been known for half a century, there is still no completely satisfactory explanation as to the pathogenesis of the brain lesions. Numerous hypotheses have been advanced stressing the relevance of such diverse factors as anoxia, anemia, antigen-antibody reaction, infection, intoxication, and liver failure. In the attempt to contribute to the clarification of this problem, the clinical and pathologic features of an apparently unique case will be presented. The patient, a 44-year-old woman, was affected by constitutional nonhemolytic hyperbilirubinemia, associated since early infancy with an "extrapyramidal" symptom complex. Post mortem, lesions of the brain were found which are consistent with the pathologic diagnosis of sequelae of kernicterus. The main feature of this case will References 1. Dubin, I. N., and Johnson, F. B.: Chronic Idiopathic Jaundice with Unidentified Pigment in Liver Cells: A New Clinico-Pathologic Entity with a Report of 12 Cases , Medicine 33:155, 1954.Crossref 2. Dutton, G. J., and Storey, I. D. E.: Uridine Components in Glucuronic Acid Metabolism: Formation of Glucuronides in Liver Suspensions , Biochem. J. 57:275, 1954. 3. Arias, I. M., and London, I. M.: Bilirubin Glucuronide Formation in Vitro: Demonstration of a Defect in Gilbert's Disease , Science 126:563, 1957.Crossref 4. Gilbert, A., and Léreboullet: La cholémie simple familiale , Gaz. hebd. méd. 49:889, 1902. 5. Dameshek, W., and Singer, K.: Familial Nonhemolytic Jaundice: Constitutional Hepatic Dysfunction with Indirect van den Bergh Reaction , Arch. Int. Med. 67:259, 1941.Crossref 6. Alwall, N.: On Hereditary, Non-Hemolytic Bilirubinemia , Acta med. scandinav. 123:560, 1946.Crossref 7. Comfort, M. W.: Constitutional Hepatic Dysfunction , M. Clin. North America 29:982, 1945. 8. Meulengracht, E.: Review of Chronic Intermittent Juvenile Jaundice , Quart. J. Med. 16:83, 1947. 9. Blanton, W. B., and Blanton, F. M.: Constitutional Hepatic Dysfunction—Familial Nonhemolytic Jaundice , Ann. Int. Med. 43:598, 1955.Crossref 10. Baroody, W. G., and Shugart, R. T.: Familial Non-Hemolytic Icterus , Am. J. Med. 20:314, 1956.Crossref 11. Schmid, R.: Direct-Reacting Bilirubin, Bilirubin Glucuronide, in Serum, Bile and Urine , Science 124:76, 1956.Crossref 12. Billing, B. H., and Lathe, G. H.: Excretion of Bilirubin as an Ester Glucuronide, Giving the Direct van den Bergh Reaction , Biochem. J. 63:6P, 1956. 13. Levvy, G. A.: Glucuronide Metabolism, with Special Reference to the Steroid Hormones , in Vitamins and Hormones: Advances and Applications , edited by R. S. Harris and K. V. Thimann, New York, Academic Press, Inc., 1956, Vol. 14, p. 267. 14. Spiller, W. G.: Severe Jaundice in the Newborn Child: A Cause of Spastic Cerebral Diplegia , Am. J. M. Sc. 149:345, 1915.Crossref 15. Ford, F. R.: Diseases of the Nervous System in Infancy, Childhood and Adolescence , Ed. 2, Springfield, Ill., Charles C Thomas, Publisher, 1944. 16. Yannet, H., and Lieberman, R.: Central Nervous System Complications Associated with Kernicterus , J. A. M. A. 130:335, 1946.Crossref 17. Lande, L.: Clinical Signs and Development of Survivors of Kernicterus Due to Rh Sensitization , J. Pediat. 32:693, 1948.Crossref 18. Pentschew, A.: Encephalopathia posticterica infantum , Arch. Psychiat. 118-180:118, 1948.Crossref 19. Evans, P. R., and Polani, P. E.: The Neurological Sequelae of Rh Sensitization , Quart. J. Med. 19:129, 1950. 20. Gerrard, J.: Kernicterus , Brain 75:526, 1952.Crossref 21. Perlstein, M.: Neurologic Sequelae of Erythroblastosis Fetalis , Am. J. Dis. Child. 79:605, 1950. 22. Crigler, J. F., Jr., and Najjar, V. A.: Congenital Familial Nonhemolytic Jaundice with Kernicterus , Pediatrics 10:169, 1952. 23. Childs, B., and Najjar, V. A.: Familial Non-Hemolytic Jaundice with Kernicterus , Pediatrics 18:369, 1956. 24. Rosenthal, I. M.; Zimmerman, H. J., and Hardy, N.: Congenital Nonhemolytic Jaundice with Disease of the Central Nervous System , Pediatrics 18:378, 1956. 25. Zimmerman, H. M., and Yannet, E.: Kernicterus: Jaundice of the Nuclear Masses of the Brain , Am. J. Dis. Child. 45:740, 1933.Crossref 26. Forster, F. M., and McCormack, R. A.: Kernicterus Unassociated with Erythroblastosis Fetalis , J. Neuropath. & Exper. Neurol. 3:379, 1944. 27. Bertrand, I.: Lésions du système nerveux central dans deux cas d'ictère nucléaire du nouvau-né , Rev. hémat. 1:399, 1946. 28. Jacob, H.: Über die Hirnschäden bei Icterus neonatorum gravis (Kernikterus) , Arch. Psychiat. 118-180:1, 1948. 29. Becker, P. F. L., and Vogel, P.: Kernicterus: A Review, with Report of 7 Cases , J. Neuropath. & Exper. Neurol. 7:190, 1948. 30. Dereymaeker, A.: Contribution à l'étude clinique, anatomique et expériméntale de l'ictère nucléaire du nouveau-né , Paris, Masson & Cie, 1949. 31. Claireaux, A.: Haemolytic Disease of the Newborn: A Clinical-Pathological Study of 157 Cases; Nuclear Jaundice (Kernicterus) , Arch. Dis. Childhood 25:61, 1950. 32. Zimmerman, H. M., and Yannet, H.: Cerebral Sequelae of Icterus Gravis Neonatorum and Their Relation to Kernikterus , Am. J. Dis. Child. 49:418, 1935. 33. Biemond, A., and van Creveld, S.: Nuclear Jaundice in Neonatal Sepsis with Jaundice , Arch. Dis. Childhood 12:173, 1937. 34. van Westrienen, A., and de Lange, C.: Atropinbehandlung bei den Folgen von Kernickterus , Jahrb. Kinderh. 150:257, 1937. 35. Fitzgerald, G. M.; Greenfield, J. G., and Kounine, B.: Neurological Sequelae of "Kernicterus," Brain 62:292, 1939. 36. Sobel, I. P., and Zucker, J. M.: Icterus Gravis Neonatorum: End Results of the Syndrome of Nuclear Jaundice , J. Pediat. 16:445, 1940. 37. van Bogaert, L.: Aspect histologique d'une séquelle tardive de l'ictère nucléaire , Ann. pædiat. 168:57, 1947. 38. Dechamps, A., and van Bogaert, L.: Idiotie, épilepsie choréoathétose double avec une syndrome médullaire, séquelles tardives de l'ictère nucléaire , Acta neurol. et psychiat. belg. 48:480, 1948. 39. Mann, L. B., Jr., and Courville, C. B.: Neurological Manifestations of Jaundice in the Newborn, with Particular Reference to the Chronic Residuals , Bull. Los Angeles Neurol. Soc. 13:69, 1948. 40. McLardy, T.: Projection of the Centromedian Nucleus of the Human Thalamus , Brain 71:290, 1948. 41. Crome, L.: Morphological Nervous Changes in Survivors of Severe Jaundice of the Newborn , J. Neurol. Neurosurg. & Psychiat. 18:17, 1955. 42. Meriwether, L. S.; Hager, H., and Scholz, W.: Kernicterus: Hypoxemia, Significant Pathogenic Factor , A. M. A. Arch. Neurol. & Psychiat. 73:293, 1955. 43. Soeken, G.: Zur Problematik der Hirnveränderungen bei Morbus hæmolyticus neonatorum , J. Hirnforsch. 2:335, 1956. 44. Brown, A. K., and Zuelzer, W. W.: Studies in Hyperbilirubinemia: I. Hyperbilirubinemia of the Newborn Unrelated to Isoimmunization , A. M. A. J. Dis. Child. 93:263, 1957.Crossref 45. Meyer, T. C.: A Study of Serum Bilirubin Levels in Relation to Kernicterus and Prematurity , Arch. Dis. Childhood 31:75, 1956.Crossref 46. Parsons, L.: The Clinician and the Rh Factor , Lancet 1:815, 1947.Crossref 47. Govan, A. D. T., and Scott, J. M.: Kernicterus and Prematurity , Lancet 1:611, 1953.Crossref 48. Pichler, M. M.: Hemolytic Disease of the Newborn , London, Oxford University Press, 1949. 49. Claireaux, A. E.; Cole, P. G., and Lathe, G. H.: Icterus of Brain in the Newborn , Lancet 2:1226, 1953.Crossref 50. Zuelzer, W. W., and Mudgett, R. T.: Kernicterus: Etiologic Study Based on an Analysis of 55 Cases , Pediatrics 6:452, 1950. 51. Hsia, D. Y.; Allen, F. H., Jr.; Gellis, S. S., and Diamond, L. K.: Erythroblastosis Fetalis: VIII. Studies of Serum Bilirubin in Relation to Kernicterus , New England J. Med. 247:668, 1952.Crossref 52. Küster, F., and Krings, H.: Die Bedeutung des Bilirubins für die Pathogenese der Hirnschadens bei der Erythroblastosis fetalis , Ztschr. Kinderh. 67:503, 1950.Crossref 53. Waters, W. J., and Britton, H. A.: Bilirubin Encephalopathy: Preliminary Studies Related to Production , Pediatrics 15:45, 1955. 54. Malloy, H. T., and Lowenstein, L.: Hereditary Jaundice in the Rat , Canad. M. A. J. 42:122, 1940. 55. Carbone, J. V., and Grodsky, G. M.: Constitutional Nonhemolytic Hyperbilirubinemia in the Rat: Defect of Bilirubin Conjugation , Proc. Soc. Exper. Biol. & Med. 94:461, 1957. 56. Lathe, G. H., and Walker, M.: An Enzyme Defect in Human Neonatal Jaundice, and in Gunn's Strain of Jaundiced Rats , Biochem. J. 67:9P, 1957. 57. Day, R. L.: Inhibition of Brain Respiration in Vitro by Bilirubin: Reversal of Inhibition by Various Means , Proc. Soc. Exper. Biol. & Med. 85:261, 1954. 58. Ernster, L.; Herlin, L., and Zetterström, R.: Experimental Studies on the Pathogenesis of Kernicterus , Pediatrics 20:6471957.

Journal

A.M.A. Archives of Neurology & PsychiatryAmerican Medical Association

Published: Jan 1, 1959

References