Alpha-fetoprotein, a fascinating protein and biomarker in neurology

Eur J Paediatr Neurol. 2014 May;18(3):243-8. doi: 10.1016/j.ejpn.2013.09.003. Epub 2013 Sep 29.


Alpha-fetoprotein (AFP) is present in fetal serum in concentrations up to 5,000,000 μg/l. After birth, AFP gene expression is turned down with a subsequent fall of the serum concentrations of this albumin-like protein to 'adult values' of circa 0.5-15 μg/l from the age of 2 years onwards. Irrespective of its assumed important functions, individuals with AFP deficiency appear fully healthy. The other way around, the presence of AFP in the circulation after the first years of life doesn't seem to harm, since individuals with 'hereditary persistence of AFP' are also without clinical abnormalities. During pregnancy, AFP (in maternal serum) has long been recognized as a marker for congenital anomalies of the fetus. Equally well known is AFP as biomarker for hepatocellular carcinoma and some other malignancies. There are at least four neurodegenerative disorders, all inherited as autosomal recessive traits and characterized by the presence of cerebellar ataxia, abnormal ocular movements, and neuropathy, for which an elevated concentration of serum AFP is an important diagnostic biomarker. The availability of a reliable biomarker is not only important during screening or diagnostic processes, but is also relevant for objective follow-up during (future) therapeutic interventions.

Keywords: AFP deficiency; Alpha-fetoprotein (AFP); Ataxia Telangiectasia; Ataxia with oculomotor apraxia type 1 and 2; Diagnostic biomarker; Hereditary persistence of AFP; Mitochondrial disorders.

Publication types

  • Review

MeSH terms

  • Animals
  • Ataxia / diagnosis*
  • Ataxia / genetics
  • Ataxia / metabolism
  • Biomarkers / metabolism*
  • Female
  • Humans
  • Neurodegenerative Diseases / diagnosis*
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism
  • Phenotype
  • Pregnancy
  • alpha-Fetoproteins / genetics
  • alpha-Fetoproteins / metabolism*


  • Biomarkers
  • alpha-Fetoproteins