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. 1998 May;35(5):353–365. doi: 10.1136/jmg.35.5.353

Hereditary fructose intolerance.

M Ali 1, P Rellos 1, T M Cox 1
PMCID: PMC1051308  PMID: 9610797

Abstract

Hereditary fructose intolerance (HFI, OMIM 22960), caused by catalytic deficiency of aldolase B (fructose-1,6-bisphosphate aldolase, EC 4.1.2.13), is a recessively inherited condition in which affected homozygotes develop hypoglycaemic and severe abdominal symptoms after taking foods containing fructose and cognate sugars. Continued ingestion of noxious sugars leads to hepatic and renal injury and growth retardation; parenteral administration of fructose or sorbitol may be fatal. Direct detection of a few mutations in the human aldolase B gene on chromosome 9q facilitates the genetic diagnosis of HFI in many symptomatic patients. The severity of the disease phenotype appears to be independent of the nature of the aldolase B gene mutations so far identified. It appears that hitherto there has been little, if any, selection against mutant aldolase B alleles in the population: in the UK, approximately 1.3% of neonates harbour one copy of the prevalent A149P disease allele. The ascendance of sugar as a major dietary nutrient, especially in western societies, may account for the increasing recognition of HFI as a nutritional disease and has shown the prevalence of mutant aldolase B genes in the general population. The severity of clinical expression correlates well with the immediate nutritional environment, age, culture, and eating habits of affected subjects. Here we review the biochemical, genetic, and molecular basis of human aldolase B deficiency in HFI, a disorder which responds to dietary therapy and in which the principal manifestations of disease are thus preventable.

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Selected References

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  1. Adelman R. C., Spolter P. D., Weinhouse S. Dietary and hormonal regulation of enzymes of fructose metabolism in rat liver. J Biol Chem. 1966 Nov 25;241(22):5467–5472. [PubMed] [Google Scholar]
  2. Alber T., Banner D. W., Bloomer A. C., Petsko G. A., Phillips D., Rivers P. S., Wilson I. A. On the three-dimensional structure and catalytic mechanism of triose phosphate isomerase. Philos Trans R Soc Lond B Biol Sci. 1981 Jun 26;293(1063):159–171. doi: 10.1098/rstb.1981.0069. [DOI] [PubMed] [Google Scholar]
  3. Ali M., Cox T. M. Diverse mutations in the aldolase B gene that underlie the prevalence of hereditary fructose intolerance. Am J Hum Genet. 1995 Apr;56(4):1002–1005. [PMC free article] [PubMed] [Google Scholar]
  4. Ali M., James C. L., Cox T. M. A newly identified aldolase B splicing mutation (G-->C, 5' intron 5) in hereditary fructose intolerance from New Zealand. Hum Mutat. 1996;7(2):155–157. doi: 10.1002/(SICI)1098-1004(1996)7:2<155::AID-HUMU11>3.0.CO;2-1. [DOI] [PubMed] [Google Scholar]
  5. Ali M., Rosien U., Cox T. M. DNA diagnosis of fatal fructose intolerance from archival tissue. Q J Med. 1993 Jan;86(1):25–30. [PubMed] [Google Scholar]
  6. Ali M., Sebastio G., Cox T. M. Identification of a novel mutation (Leu 256-->Pro) in the human aldolase B gene associated with hereditary fructose intolerance. Hum Mol Genet. 1994 Jan;3(1):203–204. doi: 10.1093/hmg/3.1.203. [DOI] [PubMed] [Google Scholar]
  7. Ali M., Tunçman G., Cross N. C., Vidailhet M., Bökesoy I., Gitzelmann R., Cox T. M. Null alleles of the aldolase B gene in patients with hereditary fructose intolerance. J Med Genet. 1994 Jun;31(6):499–503. doi: 10.1136/jmg.31.6.499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Andersson G., Brohult J., Sterner G. Increasing metabolic acidosis following fructose infusion in two children. Acta Paediatr Scand. 1969 May;58(3):301–304. doi: 10.1111/j.1651-2227.1969.tb04723.x. [DOI] [PubMed] [Google Scholar]
  9. Arnold H., Pette D. Binding of aldolase and triosephosphate dehydrogenase to F-actin and modification of catalytic properties of aldolase. Eur J Biochem. 1970 Aug;15(2):360–366. doi: 10.1111/j.1432-1033.1970.tb01016.x. [DOI] [PubMed] [Google Scholar]
  10. BLOSTEIN R., RUTTER W. J. COMPARATIVE STUDIES OF LIVER AND MUSCLE ALDOLASE. II. IMMUNOCHEMICAL AND CHROMATOGRAPHIC DIFFERENTIATION. J Biol Chem. 1963 Oct;238:3280–3285. [PubMed] [Google Scholar]
  11. Baerlocher K., Gitzelmann R., Steinmann B., Gitzelmann-Cumarasamy N. Hereditary fructose intolerance in early childhood: a major diagnostic challenge. Survey of 20 symptomatic cases. Helv Paediatr Acta. 1978 Dec;33(6):465–487. [PubMed] [Google Scholar]
  12. Banner D. W., Bloomer A. C., Petsko G. A., Phillips D. C., Pogson C. I., Wilson I. A., Corran P. H., Furth A. J., Milman J. D., Offord R. E. Structure of chicken muscle triose phosphate isomerase determined crystallographically at 2.5 angstrom resolution using amino acid sequence data. Nature. 1975 Jun 19;255(5510):609–614. doi: 10.1038/255609a0. [DOI] [PubMed] [Google Scholar]
  13. Barry R. G., St Colum, Magner J. W. Hereditary fructose intolerance in parent and child. J Ir Med Assoc. 1968 Sep;61(375):308–310. [PubMed] [Google Scholar]
  14. Beernink P. T., Tolan D. R. Disruption of the aldolase A tetramer into catalytically active monomers. Proc Natl Acad Sci U S A. 1996 May 28;93(11):5374–5379. doi: 10.1073/pnas.93.11.5374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Beernink P. T., Tolan D. R. Subunit interface mutants of rabbit muscle aldolase form active dimers. Protein Sci. 1994 Sep;3(9):1383–1391. doi: 10.1002/pro.5560030904. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Bergström J., Hultman E., Roch-Norlund A. E. Lactic acid accumulation in connection with fructose infusion. Acta Med Scand. 1968 Nov;184(5):359–364. doi: 10.1111/j.0954-6820.1968.tb02471.x. [DOI] [PubMed] [Google Scholar]
  17. Berthiaume L., Tolan D. R., Sygusch J. Differential usage of the carboxyl-terminal region among aldolase isozymes. J Biol Chem. 1993 May 25;268(15):10826–10835. [PubMed] [Google Scholar]
  18. Blom N., Sygusch J. Product binding and role of the C-terminal region in class I D-fructose 1,6-bisphosphate aldolase. Nat Struct Biol. 1997 Jan;4(1):36–39. doi: 10.1038/nsb0197-36. [DOI] [PubMed] [Google Scholar]
  19. Bode J. C., Zelder O., Rumpelt H. J., Wittkamp U. Depletion of liver adenosine phosphates and metabolic effects of intravenous infusion of fructose or sorbitol in man and in the rat. Eur J Clin Invest. 1973 Sep;3(5):436–441. doi: 10.1111/j.1365-2362.1973.tb02211.x. [DOI] [PubMed] [Google Scholar]
  20. Brooks C. C., Buist N., Tuerck J., Tolan D. R. Identification of a splice-site mutation in the aldolase B gene from an individual with hereditary fructose intolerance. Am J Hum Genet. 1991 Nov;49(5):1075–1081. [PMC free article] [PubMed] [Google Scholar]
  21. Brooks C. C., Tolan D. R. A partially active mutant aldolase B from a patient with hereditary fructose intolerance. FASEB J. 1994 Jan;8(1):107–113. doi: 10.1096/fasebj.8.1.8299883. [DOI] [PubMed] [Google Scholar]
  22. Brooks C. C., Tolan D. R. Association of the widespread A149P hereditary fructose intolerance mutation with newly identified sequence polymorphisms in the aldolase B gene. Am J Hum Genet. 1993 Apr;52(4):835–840. [PMC free article] [PubMed] [Google Scholar]
  23. CHAMBERS R. A., PRATT R. T. Idiosyncrasy to fructose. Lancet. 1956 Aug 18;271(6938):340–340. doi: 10.1016/s0140-6736(56)92196-1. [DOI] [PubMed] [Google Scholar]
  24. CORI G. T., OCHOA S., SLEIN M. W., CORI C. F. The metabolism of fructose in liver; isolation of fructose-I-phosphate and inorganic pyrophosphate. Biochim Biophys Acta. 1951 Jul;7(2):304–317. doi: 10.1016/0006-3002(51)90032-7. [DOI] [PubMed] [Google Scholar]
  25. CORNBLATH M., ROSENTHAL I. M., REISNER S. H., WYBREGT S. H., CRANE R. K. HEREDITARY FRUCTOSE INTOLERANCE. N Engl J Med. 1963 Dec 12;269:1271–1278. doi: 10.1056/NEJM196312122692401. [DOI] [PubMed] [Google Scholar]
  26. Courtois G., Baumhueter S., Crabtree G. R. Purified hepatocyte nuclear factor 1 interacts with a family of hepatocyte-specific promoters. Proc Natl Acad Sci U S A. 1988 Nov;85(21):7937–7941. doi: 10.1073/pnas.85.21.7937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Cox T. M. Aldolase B and fructose intolerance. FASEB J. 1994 Jan;8(1):62–71. doi: 10.1096/fasebj.8.1.8299892. [DOI] [PubMed] [Google Scholar]
  28. Cox T. M., Camilleri M., O'Donnell M. W., Chadwick V. S. Pseudodominant transmission of fructose intolerance in an adult and three offspring: Heterozygote detection by intestinal biopsy. N Engl J Med. 1982 Aug 26;307(9):537–540. doi: 10.1056/NEJM198208263070906. [DOI] [PubMed] [Google Scholar]
  29. Cox T. M. Iatrogenic deaths in hereditary fructose intolerance. Arch Dis Child. 1993 Oct;69(4):413–415. doi: 10.1136/adc.69.4.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Cox T. M., O'Donnell M. W., Camilleri M. Allelic heterogeneity in adult hereditary fructose intolerance. Detection of structural mutations in the aldolase B molecule. Mol Biol Med. 1983 Nov;1(4):393–400. [PubMed] [Google Scholar]
  31. Cox T. M., O'Donnell M. W., Camilleri M., Burghes A. H. Isolation and characterization of a mutant liver aldolase in adult hereditary fructose intolerance. Identification of the enzyme variant by radioassay in tissue biopsy specimens. J Clin Invest. 1983 Jul;72(1):201–213. doi: 10.1172/JCI110958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Cox T. M. Therapeutic use of fructose: professional freedom, 'pharmacovigilance' and Europe. QJM. 1995 Apr;88(4):225–227. [PubMed] [Google Scholar]
  33. Cross N. C., Cox T. M. Molecular analysis of aldolase B genes in the diagnosis of hereditary fructose intolerance in the United Kingdom. Q J Med. 1989 Nov;73(271):1015–1020. [PubMed] [Google Scholar]
  34. Cross N. C., Cox T. M. Partial aldolase B gene deletions in hereditary fructose intolerance. Am J Hum Genet. 1990 Jul;47(1):101–106. [PMC free article] [PubMed] [Google Scholar]
  35. Cross N. C., Stojanov L. M., Cox T. M. A new aldolase B variant, N334K, is a common cause of hereditary fructose intolerance in Yugoslavia. Nucleic Acids Res. 1990 Apr 11;18(7):1925–1925. doi: 10.1093/nar/18.7.1925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Cross N. C., Tolan D. R., Cox T. M. Catalytic deficiency of human aldolase B in hereditary fructose intolerance caused by a common missense mutation. Cell. 1988 Jun 17;53(6):881–885. doi: 10.1016/s0092-8674(88)90349-2. [DOI] [PubMed] [Google Scholar]
  37. Cross N. C., de Franchis R., Sebastio G., Dazzo C., Tolan D. R., Gregori C., Odievre M., Vidailhet M., Romano V., Mascali G. Molecular analysis of aldolase B genes in hereditary fructose intolerance. Lancet. 1990 Feb 10;335(8685):306–309. doi: 10.1016/0140-6736(90)90603-3. [DOI] [PubMed] [Google Scholar]
  38. DRECHSLER E. R., BOYER P. D., KOWALSKY A. G. The catalytic activity of carboxypeptidase-degraded aldolase. J Biol Chem. 1959 Oct;234:2627–2634. [PubMed] [Google Scholar]
  39. Daimon M., Tsutsumi K., Ishikawa K. DNA methylation and the regulation of aldolase B gene expression. J Biochem. 1986 Nov;100(5):1279–1286. doi: 10.1093/oxfordjournals.jbchem.a121834. [DOI] [PubMed] [Google Scholar]
  40. Danks D. M., Connellan J. M., Solomon J. R. Hereditary fructose intolerance: report of a case and comments on the hazards of fructose infusion. Aust Paediatr J. 1972 Oct;8(5):282–286. doi: 10.1111/j.1440-1754.1972.tb01838.x. [DOI] [PubMed] [Google Scholar]
  41. Dazzo C., Tolan D. R. Molecular evidence for compound heterozygosity in hereditary fructose intolerance. Am J Hum Genet. 1990 Jun;46(6):1194–1199. [PMC free article] [PubMed] [Google Scholar]
  42. Eggleston L. V., Woods H. F. Activation of liver pyruvate kinase by fructose-1-phosphate. FEBS Lett. 1970 Jan 15;6(1):43–45. doi: 10.1016/0014-5793(70)80038-2. [DOI] [PubMed] [Google Scholar]
  43. FROESCH E. R., GINSBERG J. L. Fructose metabolism of adipose tissue. I. Comparison of fructose and glucose metabolism in epididymal adipose tissue of normal rats. J Biol Chem. 1962 Nov;237:3317–3324. [PubMed] [Google Scholar]
  44. FROESCH E. R., PRADER A., LABHART A., STUBER H. W., WOLF H. P. Die hereditäre Fructoseintoleranz, eine bisher nicht bekannte kongenitale Stoffwechselstörung. Schweiz Med Wochenschr. 1957 Sep 14;87(37):1168–1171. [PubMed] [Google Scholar]
  45. FROESCH E. R., PRADER A., WOLF H. P., LABHART A. Die hereditäre Fructoseintoleranz. Helv Paediatr Acta. 1959 Jun;14(2):99–112. [PubMed] [Google Scholar]
  46. FROESCH E. R., WOLF H. P., BAITSCH H., PRADER A., LABHART A. Hereditary fructose intolerance. An inborn defect of hepatic fructose-1-phosphate splitting aldolase. Am J Med. 1963 Feb;34:151–167. doi: 10.1016/0002-9343(63)90050-0. [DOI] [PubMed] [Google Scholar]
  47. Farber G. K., Petsko G. A. The evolution of alpha/beta barrel enzymes. Trends Biochem Sci. 1990 Jun;15(6):228–234. doi: 10.1016/0968-0004(90)90035-a. [DOI] [PubMed] [Google Scholar]
  48. Gamblin S. J., Davies G. J., Grimes J. M., Jackson R. M., Littlechild J. A., Watson H. C. Activity and specificity of human aldolases. J Mol Biol. 1991 Jun 20;219(4):573–576. doi: 10.1016/0022-2836(91)90650-u. [DOI] [PubMed] [Google Scholar]
  49. Gitzelmann R., Steinmann B., Bally C., Lebherz H. G. Antibody activation of mutant human fructosediphosphate aldolase B in liver extracts of patients with hereditary fructose intolerance. Biochem Biophys Res Commun. 1974 Aug 19;59(4):1270–1277. doi: 10.1016/0006-291x(74)90451-3. [DOI] [PubMed] [Google Scholar]
  50. Gregori C., Kahn A., Pichard A. L. Activity of the rat liver-specific aldolase B promoter is restrained by HNF3. Nucleic Acids Res. 1994 Apr 11;22(7):1242–1246. doi: 10.1093/nar/22.7.1242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Gregori C., Kahn A., Pichard A. L. Competition between transcription factors HNF1 and HNF3, and alternative cell-specific activation by DBP and C/EBP contribute to the regulation of the liver-specific aldolase B promoter. Nucleic Acids Res. 1993 Feb 25;21(4):897–903. doi: 10.1093/nar/21.4.897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Grégori C., Schapira F., Kahn A., Delpech M., Dreyfus J. C. Molecular studies of liver aldolase B in hereditary fructose intolerance using blotting and immunological techniques. Ann Hum Genet. 1982 Oct;46(Pt 4):281–292. doi: 10.1111/j.1469-1809.1982.tb01579.x. [DOI] [PubMed] [Google Scholar]
  53. HERS H. G., JOASSIN G. [Anomaly of hepatic aldolase in intolerance to fructose]. Enzymol Biol Clin (Basel) 1961;1:4–14. [PubMed] [Google Scholar]
  54. HERS H. G., KUSAKA T. Le metabolisme du fructose-1-phosphate dans le foie. Biochim Biophys Acta. 1953 Jul;11(3):427–437. doi: 10.1016/0006-3002(53)90062-6. [DOI] [PubMed] [Google Scholar]
  55. HERS H. G. La fructokinase du foie. Biochim Biophys Acta. 1952 Apr;8(4):416–423. doi: 10.1016/0006-3002(52)90067-x. [DOI] [PubMed] [Google Scholar]
  56. HORECKER B. L., PONTREMOLI S., RICCI C., CHENG T. On the nature of the transaldolase-dihydroxyacetone complex. Proc Natl Acad Sci U S A. 1961 Dec 15;47:1949–1955. doi: 10.1073/pnas.47.12.1949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Hackl J. M., Balogh D., Kunz F., Dworzak E., Puschendorf B., Decristoforo A., Maier F. Postoperative Fruktoseinfusion bei wahrscheinlich hereditärer Fruktoseintoleranz. Wien Klin Wochenschr. 1978 Mar 31;90(7):237–240. [PubMed] [Google Scholar]
  58. Hartman F. C., Brown J. P. Affinity labeling of a previously undetected essential lysyl residue in class I fructose bisphosphate aldolase. J Biol Chem. 1976 May 25;251(10):3057–3062. [PubMed] [Google Scholar]
  59. Heine W., Schill H., Tessmann D., Kupatz H. Letale Leberdystrophie bei drei Geschwistern mit hereditärer Fruktoseintoleranz nach Dauertropfinfusionen mit Sorbitolhaltigen Infusionslösungen. Dtsch Gesundheitsw. 1969 Dec 4;24(49):2325–2329. [PubMed] [Google Scholar]
  60. Henry I., Gallano P., Besmond C., Weil D., Mattei M. G., Turleau C., Boué J., Kahn A., Junien C. The structural gene for aldolase B (ALDB) maps to 9q13----32. Ann Hum Genet. 1985 Jul;49(Pt 3):173–180. doi: 10.1111/j.1469-1809.1985.tb01691.x. [DOI] [PubMed] [Google Scholar]
  61. Hommes F. A., Draisma M. I. The development of L- and M-type aldolases in rat liver. Biochim Biophys Acta. 1970 Oct 27;222(1):251–252. doi: 10.1016/0304-4165(70)90380-6. [DOI] [PubMed] [Google Scholar]
  62. Ito K., Tsutsumi K., Kuzumaki T., Gomez P. F., Otsu K., Ishikawa K. A novel growth-inducible gene that encodes a protein with a conserved cold-shock domain. Nucleic Acids Res. 1994 Jun 11;22(11):2036–2041. doi: 10.1093/nar/22.11.2036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. James C. L., Rellos P., Ali M., Heeley A. F., Cox T. M. Neonatal screening for hereditary fructose intolerance: frequency of the most common mutant aldolase B allele (A149P) in the British population. J Med Genet. 1996 Oct;33(10):837–841. doi: 10.1136/jmg.33.10.837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Kai T., Sugimoto Y., Kusakabe T., Zhang R., Koga K., Hori K. Gene structure and multiple mRNA species of Drosophila melanogaster aldolase generating three isozymes with different enzymatic properties. J Biochem. 1992 Nov;112(5):677–688. doi: 10.1093/oxfordjournals.jbchem.a123958. [DOI] [PubMed] [Google Scholar]
  65. Kajihara S., Mukai T., Arai Y., Owada M., Kitagawa T., Hori K. Hereditary fructose intolerance caused by a nonsense mutation of the aldolase B gene. Am J Hum Genet. 1990 Sep;47(3):562–567. [PMC free article] [PubMed] [Google Scholar]
  66. Kaufmann U., Froesch E. R. Inhibition of phosphorylase-a by fructose-1-phosphate, alpha-glycerophosphate and fructose-1,6-diphosphate: explanation for fructose-induced hypoglycaemia in hereditary fructose intolerance and fructose-1,6-diphosphatase deficiency. Eur J Clin Invest. 1973 Sep;3(5):407–413. doi: 10.1111/j.1365-2362.1973.tb02208.x. [DOI] [PubMed] [Google Scholar]
  67. Kawahara K., Tanford C. The number of polypeptide chains in rabbit muscle aldolase. Biochemistry. 1966 May;5(5):1578–1584. doi: 10.1021/bi00869a018. [DOI] [PubMed] [Google Scholar]
  68. Kitajima Y., Takasaki Y., Takahashi I., Hori K. Construction and properties of active chimeric enzymes between human aldolases A and B. Analysis of molecular regions which determine isozyme-specific functions. J Biol Chem. 1990 Oct 15;265(29):17493–17498. [PubMed] [Google Scholar]
  69. LEVIN B., OBERHOLZER V. G., SNODGRASS G. J., STIMMLER L., WILMERS M. J. Fructosaemia: an inborn error of fructose metabolism. Arch Dis Child. 1963 Jun;38:220–230. doi: 10.1136/adc.38.199.220. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. LINDEN L., NISELL J. HEREDITAER FRUKTOSINTOLERANS. Sven Lakartidn. 1964 Oct 21;61:3185–3195. [PubMed] [Google Scholar]
  71. Lai C. Y., Nakai N., Chang D. Amino acid sequence of rabbit muscle aldolase and the structure of the active center. Science. 1974 Mar;183(130):1204–1206. doi: 10.1126/science.183.4130.1204. [DOI] [PubMed] [Google Scholar]
  72. Lameire N., Mussche M., Baele G., Kint J., Ringoir S. Hereditary fructose intolerance: a difficult diagnosis in the adult. Am J Med. 1978 Sep;65(3):416–423. doi: 10.1016/0002-9343(78)90767-2. [DOI] [PubMed] [Google Scholar]
  73. Landau B. R., Marshall J. S., Craig J. W., Hostetler K. Y., Genuth S. M. Quantitation of the pathways of fructose metabolism in normal and fructose-intolerant subjects. J Lab Clin Med. 1971 Oct;78(4):608–618. [PubMed] [Google Scholar]
  74. Lebo R. V., Tolan D. R., Bruce B. D., Cheung M. C., Kan Y. W. Spot-blot analysis of sorted chromosomes assigns a fructose intolerance disease locus to chromosome 9. Cytometry. 1985 Sep;6(5):478–483. doi: 10.1002/cyto.990060513. [DOI] [PubMed] [Google Scholar]
  75. Lench N. J., Telford E. A., Andersen S. E., Moynihan T. P., Robinson P. A., Markham A. F. An EST and STS-based YAC contig map of human chromosome 9q22.3. Genomics. 1996 Dec 1;38(2):199–205. doi: 10.1006/geno.1996.0616. [DOI] [PubMed] [Google Scholar]
  76. Levin B., Snodgrass G. J., Oberholzer V. G., Burgess E. A., Dobbs R. H. Fructosaemia. Observations on seven cases. Am J Med. 1968 Dec;45(6):826–838. doi: 10.1016/0002-9343(68)90181-2. [DOI] [PubMed] [Google Scholar]
  77. MILLER M., DRUCKER W. R., OWENS J. E., CRAIG J. W., WOODWARD H., Jr Metabolism of intravenous fructose and glucose in normal and diabetic subjects. J Clin Invest. 1952 Jan;31(1):115–125. doi: 10.1172/JCI102569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Marthaler T. M., Froesch E. R. Hereditary fructose intolerance. Dental status of eight patients. Br Dent J. 1967 Dec 19;123(12):597–599. [PubMed] [Google Scholar]
  79. Matsushima T., Kawabe S., Shibuya M., Sugimura T. Aldolase isozymes in rat tumor cells. Biochem Biophys Res Commun. 1968 Mar 12;30(5):565–570. doi: 10.1016/0006-291x(68)90090-9. [DOI] [PubMed] [Google Scholar]
  80. Mock D. M., Perman J. A., Thaler M., Morris R. C., Jr Chronic fructose intoxication after infancy in children with hereditary fructose intolerance. A cause of growth retardation. N Engl J Med. 1983 Sep 29;309(13):764–770. doi: 10.1056/NEJM198309293091305. [DOI] [PubMed] [Google Scholar]
  81. Morris A. J., Tolan D. R. Lysine-146 of rabbit muscle aldolase is essential for cleavage and condensation of the C3-C4 bond of fructose 1,6-bis(phosphate). Biochemistry. 1994 Oct 11;33(40):12291–12297. doi: 10.1021/bi00206a036. [DOI] [PubMed] [Google Scholar]
  82. Morris R. C., Jr An experimental renal acidification defect in patients with hereditary fructose intolerance. II. Its distinction from classic renal tubular acidosis; its resemblance to the renal acidification defect associated with the Fanconi syndrome of children with cystinosis. J Clin Invest. 1968 Jul;47(7):1648–1663. doi: 10.1172/JCI105856. [DOI] [PMC free article] [PubMed] [Google Scholar]
  83. Morse D. E., Chan W., Horecker B. L. The subunit structure and carboxy-terminal sequence of rabbit muscle aldolase. Proc Natl Acad Sci U S A. 1967 Aug;58(2):628–634. doi: 10.1073/pnas.58.2.628. [DOI] [PMC free article] [PubMed] [Google Scholar]
  84. Motoki K., Kitajima Y., Hori K. Isozyme-specific modules on human aldolase A molecule. Isozyme group-specific sequences 1 and 4 are required for showing characteristics as aldolase A. J Biol Chem. 1993 Jan 25;268(3):1677–1683. [PubMed] [Google Scholar]
  85. Munnich A., Besmond C., Darquy S., Reach G., Vaulont S., Dreyfus J. C., Kahn A. Dietary and hormonal regulation of aldolase B gene expression. J Clin Invest. 1985 Mar;75(3):1045–1052. doi: 10.1172/JCI111766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  86. Mäenpä P. H. Fructose-induced alterations in liver polysome profiles and Mg 2+ levels. FEBS Lett. 1972 Jul 15;24(1):37–40. doi: 10.1016/0014-5793(72)80820-2. [DOI] [PubMed] [Google Scholar]
  87. Müller-Wiefel D. E., Steinmann B., Holm-Hadulla M., Wille L., Schärer K., Gitzelmann R. Infusionsbedingtes Nieren- und Leberversagen bei undiagnostizierter hereditärer Fructose-Intoleranz. Dtsch Med Wochenschr. 1983 Jun 24;108(25):985–989. doi: 10.1055/s-2008-1069680. [DOI] [PubMed] [Google Scholar]
  88. Newbrun E., Hoover C., Mettraux G., Graf H. Comparison of dietary habits and dental health of subjects with hereditary fructose intolerance and control subjects. J Am Dent Assoc. 1980 Oct;101(4):619–626. doi: 10.14219/jada.archive.1980.0383. [DOI] [PubMed] [Google Scholar]
  89. Nordmann Y., Schapira F., Dreyfus J. C. A structurally modified liver aldolase in fructose intolerance: immunological and kinetic evidence. Biochem Biophys Res Commun. 1968 Jun 28;31(6):884–889. doi: 10.1016/0006-291x(68)90534-2. [DOI] [PubMed] [Google Scholar]
  90. Numazaki M., Tsutsumi K., Tsutsumi R., Ishikawa K. Expression of aldolase isozyme mRNAs in fetal rat liver. Eur J Biochem. 1984 Jul 2;142(1):165–170. doi: 10.1111/j.1432-1033.1984.tb08265.x. [DOI] [PubMed] [Google Scholar]
  91. Oberhaensli R. D., Rajagopalan B., Taylor D. J., Radda G. K., Collins J. E., Leonard J. V., Schwarz H., Herschkowitz N. Study of hereditary fructose intolerance by use of 31P magnetic resonance spectroscopy. Lancet. 1987 Oct 24;2(8565):931–934. doi: 10.1016/s0140-6736(87)91419-x. [DOI] [PubMed] [Google Scholar]
  92. Odièvre M., Gautier M., Rieu D. Intolérance héréditaire au fructose du nourrisson: évolution des lésions histologiques hépatiques sous traitement diététique prolongé (étude de huit observations) Arch Fr Pediatr. 1969 Apr;26(4):433–443. [PubMed] [Google Scholar]
  93. Odièvre M., Gentil C., Gautier M., Alagille D. Hereditary fructose intolerance in childhood. Diagnosis, management, and course in 55 patients. Am J Dis Child. 1978 Jun;132(6):605–608. doi: 10.1001/archpedi.1978.02120310069014. [DOI] [PubMed] [Google Scholar]
  94. PAPPER S., SAXON L. Abdominal pain occurring during the rapid administration of fructose solutions. N Engl J Med. 1957 Jan 17;256(3):132–133. doi: 10.1056/NEJM195701172560308. [DOI] [PubMed] [Google Scholar]
  95. PARKS R. E., Jr, BEN-GERSHOM E., LARDY H. A. Liver fructokinase. J Biol Chem. 1957 Jul;227(1):231–242. [PubMed] [Google Scholar]
  96. PEANASKY R. J., LARDY H. A. Bovine liver aldolase. I. Isolation, crystallization, and some general properties. J Biol Chem. 1958 Aug;233(2):365–370. [PubMed] [Google Scholar]
  97. PITKANEN E., PERHEENTUPA J. [A biochemical investigation on 2 cases of fructose intolerance]. Ann Paediatr Fenn. 1962;8:236–244. [PubMed] [Google Scholar]
  98. Penhoet E. E., Kochman M., Rutter W. J. Ioslation of fructose diphosphate aldolases A, B, and C. Biochemistry. 1969 Nov;8(11):4391–4395. doi: 10.1021/bi00839a025. [DOI] [PubMed] [Google Scholar]
  99. Penhoet E., Kochman M., Valentine R., Rutter W. J. The subunit structure of mammalian fructose diphosphate aldolase. Biochemistry. 1967 Sep;6(9):2940–2949. doi: 10.1021/bi00861a039. [DOI] [PubMed] [Google Scholar]
  100. Penhoet E., Rajkumar T., Rutter W. J. Multiple forms of fructose diphosphate aldolase in mammalian tissues. Proc Natl Acad Sci U S A. 1966 Oct;56(4):1275–1282. doi: 10.1073/pnas.56.4.1275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  101. Perheentupa J., Raivio K. Fructose-induced hyperuricaemia. Lancet. 1967 Sep 9;2(7515):528–531. doi: 10.1016/s0140-6736(67)90494-1. [DOI] [PubMed] [Google Scholar]
  102. RUTTER W. J. EVOLUTION OF ALDOLASE. Fed Proc. 1964 Nov-Dec;23:1248–1257. [PubMed] [Google Scholar]
  103. Rey M., Behrens R., Zeilinger G. Fatale Folgen einer Fructose-Infusion bei undiagnostizierter Fructose-Intoleranz. Dtsch Med Wochenschr. 1988 Jun 10;113(23):945–947. doi: 10.1055/s-2008-1067747. [DOI] [PubMed] [Google Scholar]
  104. Richardson R. M., Little J. A., Patten R. L., Goldstein M. B., Halperin M. L. Pathogenesis of acidosis in hereditary fructose intolerance. Metabolism. 1979 Nov;28(11):1133–1138. doi: 10.1016/0026-0495(79)90152-5. [DOI] [PubMed] [Google Scholar]
  105. Rosien U., Cox T. M., Ali M., Dignass A., Daul A., Layer P., Hager W. Akutes hepatorenales Versagen bei hereditärer Fructoseintoleranz. Med Klin (Munich) 1993 Sep 15;88(9):553–554. [PubMed] [Google Scholar]
  106. SCHAPIRA F., DREYFUS J. C., SCHAPIRA G. ANOMALY OF ALDOLASE IN PRIMARY LIVER CANCER. Nature. 1963 Dec 7;200:995–997. doi: 10.1038/200995a0. [DOI] [PubMed] [Google Scholar]
  107. SMITH L. H., Jr, ETTINGER R. H., SELIGSON D. A comparison of the metabolism of fructose and glucose in hepatic disease and diabetes mellitus. J Clin Invest. 1953 Apr;32(4):273–282. doi: 10.1172/JCI102736. [DOI] [PMC free article] [PubMed] [Google Scholar]
  108. Sabourin J. C., Kern A. S., Grégori C., Porteu A., Cywiner C., Châtelet F. P., Kahn A., Pichard A. L. An intronic enhancer essential for tissue-specific expression of the aldolase B transgenes. J Biol Chem. 1996 Feb 16;271(7):3469–3473. doi: 10.1074/jbc.271.7.3469. [DOI] [PubMed] [Google Scholar]
  109. Saiki R. K., Scharf S., Faloona F., Mullis K. B., Horn G. T., Erlich H. A., Arnheim N. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science. 1985 Dec 20;230(4732):1350–1354. doi: 10.1126/science.2999980. [DOI] [PubMed] [Google Scholar]
  110. Sakakibara M., Takahashi I., Takasaki Y., Mukai T., Hori K. Construction and expression of human aldolase A and B expression plasmids in Escherichia coli host. Biochim Biophys Acta. 1989 Apr 12;1007(3):334–342. doi: 10.1016/0167-4781(89)90156-5. [DOI] [PubMed] [Google Scholar]
  111. Santamaria R., Scarano M. I., Esposito G., Chiandetti L., Izzo P., Salvatore F. The molecular basis of hereditary fructose intolerance in Italian children. Eur J Clin Chem Clin Biochem. 1993 Oct;31(10):675–678. doi: 10.1515/cclm.1993.31.10.675. [DOI] [PubMed] [Google Scholar]
  112. Santamaria R., Tamasi S., Del Piano G., Sebastio G., Andria G., Borrone C., Faldella G., Izzo P., Salvatore F. Molecular basis of hereditary fructose intolerance in Italy: identification of two novel mutations in the aldolase B gene. J Med Genet. 1996 Sep;33(9):786–788. doi: 10.1136/jmg.33.9.786. [DOI] [PMC free article] [PubMed] [Google Scholar]
  113. Saxén L., Jousimies-Somer H., Kaisla A., Kanervo A., Summanen P., Sipilä I. Subgingival microflora, dental and periodontal conditions in patients with hereditary fructose intolerance. Scand J Dent Res. 1989 Apr;97(2):150–158. doi: 10.1111/j.1600-0722.1989.tb01444.x. [DOI] [PubMed] [Google Scholar]
  114. Schapira F., Hatzfeld A., Gregori C. Studies on liver aldolases in hereditary fructose intolerance. Enzyme. 1974;18(1):73–83. doi: 10.1159/000459415. [DOI] [PubMed] [Google Scholar]
  115. Schulte M. J., Lenz W. Fatal sorbitol infusion in patient with fructose-sorbitol intolerance. Lancet. 1977 Jul 23;2(8030):188–188. doi: 10.1016/s0140-6736(77)90197-0. [DOI] [PubMed] [Google Scholar]
  116. Sebastio G., de Franchis R., Strisciuglio P., Andria G., Dionisi Vici C., Sabetta G., Gatti R., Cross N. C., Cox T. M. Aldolase B mutations in Italian families affected by hereditary fructose intolerance. J Med Genet. 1991 Apr;28(4):241–243. doi: 10.1136/jmg.28.4.241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  117. Shaw-Lee R., Lissemore J. L., Sullivan D. T., Tolan D. R. Alternative splicing of fructose 1,6-bisphosphate aldolase transcripts in Drosophila melanogaster predicts three isozymes. J Biol Chem. 1992 Feb 25;267(6):3959–3967. [PubMed] [Google Scholar]
  118. Sia C. L., Horecker B. L. The molecular weight of rabbit muscle aldolase and the properties of the subunits in acid solution. Arch Biochem Biophys. 1968 Jan;123(1):186–194. doi: 10.1016/0003-9861(68)90118-5. [DOI] [PubMed] [Google Scholar]
  119. Steegmanns I., Rittmann M., Bayerl J. R., Gitzelmann R. Erwachsene mit hereditärer Fructoseintoleranz: Gefährdung durch Fructoseinfusion. Dtsch Med Wochenschr. 1990 Apr 6;115(14):539–541. doi: 10.1055/s-2008-1065044. [DOI] [PubMed] [Google Scholar]
  120. Steinmann B., Gitzelmann R. The diagnosis of hereditary fructose intolerance. Helv Paediatr Acta. 1981 Sep;36(4):297–316. [PubMed] [Google Scholar]
  121. Stuart D. I., Levine M., Muirhead H., Stammers D. K. Crystal structure of cat muscle pyruvate kinase at a resolution of 2.6 A. J Mol Biol. 1979 Oct 15;134(1):109–142. doi: 10.1016/0022-2836(79)90416-9. [DOI] [PubMed] [Google Scholar]
  122. Sygusch J., Beaudry D., Allaire M. Molecular architecture of rabbit skeletal muscle aldolase at 2.7-A resolution. Proc Natl Acad Sci U S A. 1987 Nov;84(22):7846–7850. doi: 10.1073/pnas.84.22.7846. [DOI] [PMC free article] [PubMed] [Google Scholar]
  123. Takahashi I., Takasaki Y., Hori K. Site-directed mutagenesis of human aldolase isozymes: the role of Cys-72 and Cys-338 residues of aldolase A and of the carboxy-terminal Tyr residues of aldolases A and B. J Biochem. 1989 Feb;105(2):281–286. doi: 10.1093/oxfordjournals.jbchem.a122654. [DOI] [PubMed] [Google Scholar]
  124. Thurston J. H., Jones E. M., Hauhart R. E. Decrease and inhibition of liver glycogen phosphorylase after fructose. An experimental model for the study of hereditary fructose intolerance. Diabetes. 1974 Jul;23(7):597–604. doi: 10.2337/diab.23.7.597. [DOI] [PubMed] [Google Scholar]
  125. Tolan D. R., Brooks C. C. Molecular analysis of common aldolase B alleles for hereditary fructose intolerance in North Americans. Biochem Med Metab Biol. 1992 Aug;48(1):19–25. doi: 10.1016/0885-4505(92)90043-x. [DOI] [PubMed] [Google Scholar]
  126. Tolan D. R., Niclas J., Bruce B. D., Lebo R. V. Evolutionary implications of the human aldolase-A, -B, -C, and -pseudogene chromosome locations. Am J Hum Genet. 1987 Nov;41(5):907–924. [PMC free article] [PubMed] [Google Scholar]
  127. Tolan D. R., Penhoet E. E. Characterization of the human aldolase B gene. Mol Biol Med. 1986 Jun;3(3):245–264. [PubMed] [Google Scholar]
  128. Tsutsumi K., Ito K., Ishikawa K. Developmental appearance of transcription factors that regulate liver-specific expression of the aldolase B gene. Mol Cell Biol. 1989 Nov;9(11):4923–4931. doi: 10.1128/mcb.9.11.4923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  129. Tsutsumi K., Ito K., Yabuki T., Ishikawa K. A1F-B, a novel CCAAT-binding transcription activator that interacts with the aldolase B promoter. FEBS Lett. 1993 Apr 19;321(1):51–54. doi: 10.1016/0014-5793(93)80619-6. [DOI] [PubMed] [Google Scholar]
  130. Tsutsumi K., Tsutsumi R., Ishikawa K. Tissue-specific changes in chromatin structure of the rat aldolase B locus. J Biochem. 1987 Nov;102(5):1013–1021. doi: 10.1093/oxfordjournals.jbchem.a122139. [DOI] [PubMed] [Google Scholar]
  131. VANDERHEIDEN B. S., MEINHART J. O., DODSON R. G., KREBS E. G. The preparation and properties of crystalline yeast aldolase. J Biol Chem. 1962 Jul;237:2095–2098. [PubMed] [Google Scholar]
  132. Van Den Berghe G., Hue L., Hers H. G. Effect of administration of the fructose on the glycogenolytic action of glucagon. An investigation of the pathogeny of hereditary fructose intolerance. Biochem J. 1973 Jun;134(2):637–645. doi: 10.1042/bj1340637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  133. WOLF H., ZSCHOCKE D., WEDEMEYER F. W., HUBNER W. Angeborene hereditäre Fructose-Intoleranz. Klin Wochenschr. 1959 Jul 1;37(13):693–696. doi: 10.1007/BF01478217. [DOI] [PubMed] [Google Scholar]
  134. Watts R. W., Watts J. E., Seegmiller J. E. Xanthine oxidase activity in human tissues and its inhibition by allopurinol (4-hydroxypyrazolo[3,4-d] pyrimidine). J Lab Clin Med. 1965 Oct;66(4):688–697. [PubMed] [Google Scholar]
  135. Weiss T. L., Zieske J. D., Bernstein I. A. Reversible microsomal binding of hepatic aldolase. Biochim Biophys Acta. 1981 Oct 13;661(2):221–229. doi: 10.1016/0005-2744(81)90007-3. [DOI] [PubMed] [Google Scholar]
  136. Woods H. F., Alberti K. G. Dangers of intravenous fructose. Lancet. 1972 Dec 23;2(7791):1354–1357. doi: 10.1016/s0140-6736(72)92791-2. [DOI] [PubMed] [Google Scholar]
  137. Woods H. F., Eggleston L. V., Krebs H. A. The cause of hepatic accumulation of fructose 1-phosphate on fructose loading. Biochem J. 1970 Sep;119(3):501–510. doi: 10.1042/bj1190501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  138. Zalitis J., Oliver I. T. Inhibition of glucose phosphate isomerase by metabolic intermediates of fructose. Biochem J. 1967 Mar;102(3):753–759. doi: 10.1042/bj1020753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  139. Zhang R., Kai T., Sugimoto Y., Kusakabe T., Takasaki Y., Koga K., Hori K. Drosophila melanogaster aldolase: characterization of the isozymes alpha, beta, and gamma generated from a single gene. J Biochem. 1995 Jul;118(1):183–188. doi: 10.1093/oxfordjournals.jbchem.a124876. [DOI] [PubMed] [Google Scholar]
  140. Zhao Y., Tsutsumi R., Yamaki M., Nagatsuka Y., Ejiri S., Tsutsumi K. Initiation zone of DNA replication at the aldolase B locus encompasses transcription promoter region. Nucleic Acids Res. 1994 Dec 11;22(24):5385–5390. doi: 10.1093/nar/22.24.5385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  141. van den Berghe G., Bronfman M., Vanneste R., Hers H. G. The mechanism of adenosine triphosphate depletion in the liver after a load of fructose. A kinetic study of liver adenylate deaminase. Biochem J. 1977 Mar 15;162(3):601–609. doi: 10.1042/bj1620601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  142. von Ruecker A., Endres W., Shin Y. S., Butenandt I., Steinmann B., Gitzelmann R. A case of fatal hereditary fructose intolerance. Misleading information of formula composition. Helv Paediatr Acta. 1981;36(6):599–600. [PubMed] [Google Scholar]

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