Alpha-fetoprotein, a fascinating protein and biomarker in neurology

Ataxia telangiectasia: presentation and diagnostic delay

“…AFP levels are not specific to A-T and can be raised in some other neurodegenerative conditions characterised by the presence of cerebellar ataxia, abnormal ocular movements and neuropathy, but results are rarely normal in patients with A-T 3. Other neurodegenerative disorders that should be considered when encountering a child with ataxia and increased serum AFP include ataxia with oculomotor apraxia type 1 (AOA1) and ataxia with oculomotor apraxia type 2 (AOA2).…”

“…In AOA1, the AFP levels are normal and telangiectasias and immunological problems do not tend to occur. In AOA2, the AFP levels are lower than in classic A-T and it has a much later onset (usually between 12 and 20 years of age) and is more common than A0A1 3. Milder variants of A-T that have some activity of ATM kinase are more common in the UK and in some cases diagnosis is significantly delayed, even until adulthood in milder forms.…”

Prenatal growth restriction, retinal dystrophy, diabetes insipidus and white matter disease: expanding the spectrum of PRPS1-related disorders

“…To date, it remains unclear if AFP is only a biochemical marker of the disease or if it contributes to the disease-causing mechanisms. 19 This report adds severe PRS-1 deficiency to the group of disorders that need to be considered in the context of elevated MS-AFP.…”

“…17,18 AFP is a member of the albumin gene family and it is presumed to have a function in chemotaxis, oxygen free radical scavenging and lipid peroxidation. 19 It is produced predominantly during fetal life when it reaches peak levels in the third trimester, declining rapidly after birth. Serum AFP is also elevated in certain neurodegenerative disorders such as ataxia telangiectasia, ataxia with oculomotor apraxia type 2 and some mitochondrial depletion syndromes.…”

Polynucleotide kinase-phosphatase (PNKP) mutations and neurologic disease

“…A clinically related syndrome AOA2, is caused by mutations in Senataxin (Anheim et al, 2009; Hammer et al, 2012; Le Ber et al, 2004; Moreira et al, 2004), a helicase, which is associated with DNA damage responses, transcriptional control and possibly a SSBR defect (Bennett and La Spada, 2015; Hamperl and Cimprich, 2014; Richard et al, 2013; Suraweera et al, 2007). AOA2 has an older age onset (mean 14.6 years) and affected individuals rarely manifest dystonia and have normal albumin and cholesterol values, but consistently have increased alpha-fetoprotein (Anheim et al, 2012; Schieving et al, 2014). In contrast, AOA3 is reported to result from mutations in the phosphoinositide-3-kinase regulatory subunit 5 (PIK3R5) gene, and cell lines from these patients have been linked to defective DNA damage signaling (Al Tassan et al, 2012; Gueven et al, 2007; Kobayashi et al, 2015).…”