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Homocystinuria

  • Charles Marques Lourenço
Chapter

Abstract

Classical Homocystinuria is an autosomal recessive and multisystemic metabolic disorder, caused mainly by mutations in cystathionine beta-synthase (CBS) enzyme involved in methionine metabolism. The frequency of CBS deficiency is variable, being reported in different ranges [1:65,000 to 1:900,000]. The age of onset and severity of symptoms can be extremely variable, ranging from severely affected children to near asymptomatic adults. Two “clinical-biochemical” phenotypes are usually described in CBS deficiency: the so-called B6-responsive homocystinuria and B6-non-responsive homocystinuria. B6-responsive patients have typically - but not always - milder symptons than the non-responsive patients since they have higher residual enzyme levels.

Keywords

Homocystinuria Cystathionine beta-synthase enzyme Psychiatric complications of homocystinuria Pyridoxine treatment for homocystinuria Hyperhomocysteinemia-induced deep vein thrombosis Thrombosis in patient with homocystinuria 

References

  1. 1.
    Yap S. Homocystinuria due to cystathionine β-synthase deficiency. In: Saudubray J-M, editor. Orphanet; 2005.Google Scholar
  2. 2.
    Gan-Schreier H, Kebbewar M, Fang-Hoffmann J, Wilrich J, Abdoh G, Ben-Omran T, et al. Newborn population screening for classic homocystinuria by determination of total homocysteine from Guthrie cards. J Pediatr. 2010;156(3):427–32.CrossRefPubMedGoogle Scholar
  3. 3.
    Naughten ER, Yap S, Mayne PD. Newborn screening for homocystinuria: Irish and world experience. Eur J Pediatr. 1998;157(Suppl. 2):S84–7.CrossRefPubMedGoogle Scholar
  4. 4.
    Refsum H, Fredriksen A, Meyer K, Ueland PM, Kase BF. Birth prevalence of homocystinuria. J Pediatr. 2004;144(6):830–2.PubMedGoogle Scholar
  5. 5.
    Zschocke J, Kebbewar M, Gan-Schreier H, et al. Molecular neonatal screening for homocystinuria in the Qatari population. Hum Mutat. 2009;30(6):1021–2.CrossRefPubMedGoogle Scholar
  6. 6.
    Finkelstein JD, Mudd SH, Irreverre F, Laster L. Homocystinuria due to cystathionine synthetase deficiency: the mode of inheritance. Science (New York, NY). 1964;146(3645):785–7.CrossRefGoogle Scholar
  7. 7.
    Carson NA, Neill DW. Metabolic abnormalities detected in a survey of mentally backward individuals in Northern Ireland. Arch Dis Child. 1962;37:505–13.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Burke JP, O’Keefe M, Bowell R, Naughten ER. Ocular complications in homocystinuria —early and late treated. Br J Ophthalmol. 1989;73(6):427–31.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Brenton DP, Dow CJ, James JI, Hay RL, Homocystinuria W-DR. Marfan’s syndrome: A comparison. J Bone Joint Surg. 1972;54(2):277–98.CrossRefGoogle Scholar
  10. 10.
    Mudd SH, Levy HL, Skovby F. Disorders of transsulfuration. In: Scriver CR, Beaudet AL, Sly WS, Valle D, editors. The metabolic and molecular bases of inherited disease. 7th ed. New York: McGraw-Hill; 1995. p. 1279–327.Google Scholar
  11. 11.
    Carson NAJ. Homocystinuria: clinical and biochemical heterogeneity. In: Cockburn F, Gitzelmann R, editors. Inborn errors of metabolism in humans. Lancaster: MTP Press Limited; 1982. p. 53–67.CrossRefGoogle Scholar
  12. 12.
    Erol M, Gayret OB, Yigit O, Serefoglu Cabuk K, Toksoz M, Tiras M. A case of homocystinuria misdiagnosed as moyamoya disease: a case report. Iran Red Crescent Med J. 2016;18(4):e30332.  https://doi.org/10.5812/ircmj.30332. eCollection 2016 AprCrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Andria G, Sebastio G. Homocystinuria due to cystathionine b-synthase deficiency and related disorders. In: Fernandes J, Saudubray J-M, Van Den Berghe G, editors. Inborn metabolic diseases diagnosis and treatment. 2nd ed. New York: Springer; 1996. p. 177–82.Google Scholar
  14. 14.
    Woods E, Dawson C, Senthil L, Geberhiwot T. Cerebral venous thrombosis as the first presentation of classical homocystinuria in an adult patient. BMJ Case Rep. 2017. pii: bcr2016217477.  https://doi.org/10.1136/bcr-2016-217477.
  15. 15.
    Oliveira Santos M, Geraldes R, Conceição I. Peripheral nerve involvement in classic homocystinuria: an unusual association. BMJ Case Rep. 2016. pii: bcr2016216255.  https://doi.org/10.1136/bcr-2016-216255.
  16. 16.
    Majtan T, Pey AL, Ereño-Orbea J, Martínez-Cruz LA, Kraus JP. Targeting cystathionine beta-synthase misfolding in homocystinuria by small ligands: state of the art and future directions. Curr Drug Targets. 2016;17(13):1455–70. ReviewCrossRefPubMedGoogle Scholar
  17. 17.
    Majtan T, Pey AL, Kraus JP. Kinetic stability of cystathionine beta-synthase can be modulated by structural analogs of S-adenosylmethionine: potential approach to pharmacological chaperone therapy for homocystinuria. Biochimie. 2016;126:6–13.  https://doi.org/10.1016/j.biochi.2016.01.009. Epub 2016 Jan 20.CrossRefPubMedGoogle Scholar
  18. 18.
    Gao L, Kolanuvada B, Naik G, Zhang Y, Zhao M, Sun L, Alaie D, Petrillo RL. Hyperhomocysteinemia-induced upper extremity deep vein thrombosis and pulmonary embolism in a patient with methyltetrahydrofolate reductase mutation: a case report and literature review. Blood Coagul Fibrinolysis. 2016;27(6):720–3.  https://doi.org/10.1097/MBC.0000000000000458.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Neurology, Neurogenetics Unit, Clinics Hospital of Ribeirao PretoUniversity of Sao Paulo, School of Medicine of Ribeirao PretoSao PauloBrazil
  2. 2.Clinical Genetics, Centro Universitario Estacio de Ribeirao PretoSao PauloBrazil

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