Congenital Deficiency versus Hereditary Persistence of Human Alpha-fetoprotein: A Meta-analysis and Overview of Potential Biomedical Consequences

Gerald Mizejewski

doi:10.17334/jps.81128

Congenital Deficiency versus Hereditary Persistence of Human Alpha-fetoprotein: A Meta-analysis and Overview of Potential Biomedical Consequences

Year 2012, Volume: 4 Issue: 2, 1 - 19, 26.05.2012

Gerald Mizejewski

Abstract

Human alpha-fetoprotein (AFP) is a 70 kD tumor-associated fetal protein (oncofetal protein) which has been utilized clinically as a biomarker for both multiple cancers and for fetal defects including neural tube defects and chromosomal abnormalities. Extreme low and high levels of serum AFP in conjunction with gene mutations have now been established in disorders such as congenital deficiency (CD) and hereditary persistence (HP) of AFP. The objectives of the present review are to compare the clinical manifestations and analyze the mutational basis of these two AFP genetic disorders in accordance with presently accepted models of AFP gene regulation. The regulatory elements of AFP gene expression i.e., enhancers, promoters, and silencers are described in light of the genetic alterations expressed by the CD- and HP-AFP patients. By use of structure/function peptide mapping of the full-length AFP amino acid sequence, the potential biomedical consequences exhibited by CD-AFP and HP-AFP patients are presented and discussed. A new prospective on placental dysfunction in these AFP genetic disorders has also been introduced. Using AFP reference levels in maternal serum, cord blood, newborn blood, pediatric and adult serum, AFP serum concentrations are presented that could alert the obstetrician of potential CD-AFP during pregnancy. Knowledge of such serum values could provide tools to allow clinicians to distinguish between adult HP-AFP and malignant/non-malignant diseases such as liver and germ cell tumors, cirrhosis, hepatitis, and various liver disorders. Knowledge of AFP reference levels might serve to guide the clinician in avoiding: a) misguided diagnoses; b) unnecessary treatments and therapies; and c) undue anxieties and stress during pregnant and non-pregnant states.

Keywords

alpha-fetoprotein, genetic disorder, autosomal recessive, autosomal dominant, gene mutation, pedigree, deficiency, persistence

References

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Year 2012, Volume: 4 Issue: 2, 1 - 19, 26.05.2012

Gerald Mizejewski

Abstract

References

1. Abelev GI, Eraiser TL. Cellular aspects of alphafetoprotein reexpression in tumors. Seminars in Cancer Biology. 1999; 9: 95-107.
2. Mizejewski GJ. Alpha-fetoprotein as a biologic response modifier: relevance to domain and subdomain structure. Proc Soc Exp Biol Med. 1997; 215: 333-62.,
3. Gonzalez SA, Keeffe EB. Diagnosis of hepatocellular carcinoma: role of tumor markers and liver biopsy. Clin Liver Dis. 2011; 15: 297-306.
4. Mizejewski GJ. Physiology of alpha-fetoprotein as a biomarker for perinatal distress: relevance to adverse pregnancy outcome. Exp Biol Med (Maywood). 2007; 232: 993-1004.
5. Mizejewski GJ. Levels of alpha-fetoprotein during pregnancy and early infancy in normal and disease states. Obstet Gynecol Surv. 2003; 58: 804-26.
6. Bader D, Riskin A, Vafsi O, et al. Alpha-fetoprotein in the early neonatal period--a large study and review of the literature. Clin Chim Acta. 2004; 349: 15-23.
7. Masseyeff R, Gilli J, Krebs B, Calluaud A, Bonet C. Evolution of alpha-fetoprotein serum levels throughout life in humans and rats, and during pregnancy in the rat. Ann N Y Acad Sci. 1975; 259: 17-28.
8. Mizejewski GJ. Biological roles of alpha-fetoprotein during pregnancy and perinatal development. Exp Biol Med (Maywood). 2004; 229: 439-63.
9. Crandall BF. Alpha-fetoprotein: a review. Crit Rev Clin Lab Sci. 1981; 15: 127-85.
10.Crandall BF, Chua C. Risks for fetal abnormalities after very and moderately elevated AF-AFPs. Prenat Diagn. 1997; 17: 837-41.
11. Mizejewski GJ, Carter TP, Beblowski DW, Bellisario R. Measurement of serum alpha-fetoprotein in early infancy: utilization of dried blood specimens. Pediatr Res. 1983; 17: 47-50.
12.Caceres G, Dauphinee MJ, Eisele LE, MacColl R, Mizejewski GJ. Anti-prostate cancer and anti-breast cancer activities of two peptides derived from alphafetoprotein. Anticancer Res. 2002; 22: 2817-20.
13. Mizejewski GJ, Bellisario R, Carter TP. Birth weight and alpha-fetoprotein in the newborn. Pediatrics. 1984; 73: 736-7.
14.Blohm MEG, Vesterling-Horner D, Calaminus G, Gobel U. Alpha1-fetoprotein (AFP) reference values in infants up to 2 years of age. Pediatr Hematol Oncol 1998; 15: 135-42.
15.Christiansen M, Hogdall CK, Andersen JR, NorgaardPedersen B. Alpha-fetoprotein in plasma and serum of healthy adults: preanalytical, analytical and biological sources of variation and construction of age-dependent reference i ntervals. Scand J Clin Lab Invest. 2001; 61: 205-15.
16. Kashyap R, Jain A, Nalesnik M, et al. Clinical significance of elevated alpha-fetoprotein in adults and children. Dig Dis Sci. 2001; 46: 1709-13.
17. La'ulu SL, Rasmussen KJ, Robert WL. Pediatric reference intervals for serum alpha-fetoprotein. Clin Chim Acta. 2011; 412: 1695-6.
18. Haddow JE, Palomaki GE, Knight GJ, et al. Prenatal screening for Down's syndrome with use of maternal serum markers. N Engl J Med. 1992; 327: 588-93.
19. Mizejewski GJ. Alpha-Fetoprotein. In: Hickman PE, Koerbin G, editors. Methods in Clinical Chemistry: Pesce Kaplan Publishers; 2009.
20.Brock DJ, Bolton AE, Monaghan JM. Prenatal diagnosis of anencephaly through maternal serumalphafetoprotein measurement. Lancet. 1973; 2: 923-4.
21. Leek AE, Ruoss CF, Kitau MJ, Chard T. Raised alphafetoprotein in maternal serum with anencephalic pregnancy. Lancet. 1973; 2: 385.
22.Cuckle HS, Holding S, Jones R, Groome NP, Wallace EM. Combining inhibin A with existing secondtrimester markers in maternal serum screening for Down's syndrome. Prenat Diagn. 1996; 16: 1095-100.
23. Thomas RL, Blakemore KJ. Evaluation of elevations in maternal serum alpha-fetoprotein: a review. Obstet Gynecol Surv. 1990; 45: 269-83.
24.Brock DJ, Sutcliffe RG. Alpha-fetoprotein in the antenatal diagnosis of anencephaly and spina bifida. Lancet. 1972; 2: 197-9.
25.Benn PA, Craffey A, Horne D, Ramsdell L, Rodis JF. Elevated maternal serum alpha-fetoprotein with low unconjugated estriol and the risk for lethal perinatal outcome. J Matern Fetal Med. 2000; 9: 165-9.
26.Bartha JL, Comino-Delgado R, Arce F, Alba P, Broullon JR, Barahona M. Relationship between alphafetoprotein and fetal erythropoiesis. J Reprod Med. 1999; 44: 689-97.
27.Bartha JL, Illanes S, Abdel-Fattah SA, Harrison G, Soothill PW. Maternal serum alpha-fetoprotein, fetal middle cerebral artery blood flow velocity and fetal haemoglobin in pregnancies at risk of fetal anaemia. Prenat Diagn. 2006; 26: 101-4.
28. Mizejewski G. New insights into AFP structure and function: Potential biomedical applications. Mizejewski G, Porter IH, editors. Orlando: Academic Press; 1985.
29. Norgaard-Pedersen B, Klebe JG. Alpha 1-fetoprotein and carbonic anhydrase B and C concentration in cord blood from newborn infants of diabetic mothers. Acta Endocrinol Suppl (Copenh). 1974; 182: 81-6.
30. Mizejewski GJ, Bellisario R,Beblowski DW,Carter TP. Adaptation of commercial radioimmunoassay kit for measurement of alpha-fetoprotein in dried blood specimens from newborns.Clin Chem.1982;28:1207- 10.
31.Bloomer JR, Waldmann TA, McIntire KR, Klatskin G. alpha-fetoprotein in noneoplastic hepatic disorders. JAMA. 1975; 233: 38-41.
32.Ruoslahti E, Seppala M. Normal and increased alphafetoprotein in neoplastic and non-neoplastic liver disease. Lancet. 1972; 300: 278-9.
33.Bei R, Mizejewski GJ. Alpha fetoprotein is more than a hepatocellular cancer biomarker: from spontaneous immune response in cancer patients to the development of an AFP-based cancer vaccine. Curr Mol Med. 2011; 11: 564-81.
34. Dourov N, Mayer R, de Martelaere F, Godart S, Gepts W, Maurus R. Melanotic neuroectodermal tumor of infancy with high serum levels of alpha-fetoprotein. Ultrastructural study and immunological evidence of glial fibrillary protein and alpha-fetoprotein. J Oral Pathol. 1987; 16: 251-5.
35. Schneider DT, Calaminus G, Gobel U. Diagnostic value of alpha 1-fetoprotein and beta-human chorionic gonadotropin in infancy and childhood. Pediatr Hematol Oncol. 2001; 18: 11-26.
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There are 110 citations in total.

Details

Primary Language	English
Journal Section	Reviews
Authors	Gerald Mizejewski
Publication Date	May 26, 2012
Published in Issue	Year 2012 Volume: 4 Issue: 2

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APA	Mizejewski, G. (2012). Congenital Deficiency versus Hereditary Persistence of Human Alpha-fetoprotein: A Meta-analysis and Overview of Potential Biomedical Consequences. Journal of Pediatric Sciences, 4(2), 1-19. https://doi.org/10.17334/jps.81128
AMA	Mizejewski G. Congenital Deficiency versus Hereditary Persistence of Human Alpha-fetoprotein: A Meta-analysis and Overview of Potential Biomedical Consequences. Journal of Pediatric Sciences. June 2012;4(2):1-19. doi:10.17334/jps.81128
Chicago	Mizejewski, Gerald. “Congenital Deficiency Versus Hereditary Persistence of Human Alpha-Fetoprotein: A Meta-Analysis and Overview of Potential Biomedical Consequences”. Journal of Pediatric Sciences 4, no. 2 (June 2012): 1-19. https://doi.org/10.17334/jps.81128.
EndNote	Mizejewski G (June 1, 2012) Congenital Deficiency versus Hereditary Persistence of Human Alpha-fetoprotein: A Meta-analysis and Overview of Potential Biomedical Consequences. Journal of Pediatric Sciences 4 2 1–19.
IEEE	G. Mizejewski, “Congenital Deficiency versus Hereditary Persistence of Human Alpha-fetoprotein: A Meta-analysis and Overview of Potential Biomedical Consequences”, Journal of Pediatric Sciences, vol. 4, no. 2, pp. 1–19, 2012, doi: 10.17334/jps.81128.
ISNAD	Mizejewski, Gerald. “Congenital Deficiency Versus Hereditary Persistence of Human Alpha-Fetoprotein: A Meta-Analysis and Overview of Potential Biomedical Consequences”. Journal of Pediatric Sciences 4/2 (June 2012), 1-19. https://doi.org/10.17334/jps.81128.
JAMA	Mizejewski G. Congenital Deficiency versus Hereditary Persistence of Human Alpha-fetoprotein: A Meta-analysis and Overview of Potential Biomedical Consequences. Journal of Pediatric Sciences. 2012;4:1–19.
MLA	Mizejewski, Gerald. “Congenital Deficiency Versus Hereditary Persistence of Human Alpha-Fetoprotein: A Meta-Analysis and Overview of Potential Biomedical Consequences”. Journal of Pediatric Sciences, vol. 4, no. 2, 2012, pp. 1-19, doi:10.17334/jps.81128.
Vancouver	Mizejewski G. Congenital Deficiency versus Hereditary Persistence of Human Alpha-fetoprotein: A Meta-analysis and Overview of Potential Biomedical Consequences. Journal of Pediatric Sciences. 2012;4(2):1-19.

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