Alpha-1-antitrypsin Phenotyping & Genotyping
Biochemistry Overview / Directory
Purpose of the test
Alpha-1-antitrypsin (A1AT) deficiency may manifest itself in a range of ways from liver disease in the neonatal period to lung disease in adult life depending on the mutation present (i.e. Z or S mutations). Whilst measurement of A1AT concentrations can be useful as a first line screen for deficiency, as A1AT is an acute phase protein, concentrations can approach the normal reference range in acutely ill subjects. Phenotyping, using isoelectric focusing, allows the mutation to be identified and the screening of siblings or other members of the family, who may be asymptomatic at the time.
A1AT genotype analysis is offered as an adjunct to the phenotyping service, for family studies and for prenatal diagnosis (which must be discussed and pre-arranged). Homozygosity or heterozygosity for the Z and S mutations can be detected using the Elucigene TM kit (Tepnel Diagnostics Ltd); other variants are not detected by this method, which is based on the Amplification Refractory Mutation System (ARMS TM).
Sample Requirements
Phenotyping: Serum or EDTA plasma (250 µL) : note heparin samples are NOT suitable.
Genotyping: 1 mL EDTA whole blood (smaller samples may be acceptable from infants/neonates, please ring to discuss).
DNA
Mouthwash samples are acceptable if unable to obtain a blood sample or if recently transfused.
Chorion villus tissue (CVS) or DNA for prenatal diagnosis.
Storage and Transport
Send by overnight first class post (unless for prenatal diagnosis, in which case please send by courier).
Turnaround Time
Phenotyping is carried out once a week. For routine genotyping 3-4 weeks, within 1 week for prenatal diagnosis.
Price
Prices available on application - please contact adrian.turner@kch.nhs.uk. Discounts could be available for significant workloads.
Contacts
Dr Roy Sherwood
Tel: 020 3299 3726
e-mail: roy.sherwood@nhs.net
Dr Hagosa Abraha
Tel: 020 3299 4134
e-mail: hagosa.abraha@kch.nhs.uk
References
Hinds R, Hadchouel A, Shanmugham NP, Al-Hussaini A, Chambers S, Cheesman P, Mieli-Vergani G, Hadzic D. (2006) Variable degree of liver involvement in siblings with PiZZ alpha-1- antitrypsin deficiency related liver disease. J Paed Gastroenterol Nutr 43: 136-8
Francavilla R, Castellaneta SP, Hadzic N, Chambers SM, Portmann B, Tung J, Cheeseman P, Rela M, Heaton ND, Mieli-Vergani G (2000) Prognosis of alpha-1-antitrypsin deficiency-related liver disease in the era of paediatric liver transplantation. J Hepatol 32: 986-92
Ambrose HJ, Chambers SM, Mieli-Vergani G, Ferrie R, Newton CR, Robertson NH (1999) Molecular characterization of a new alpha-1-antitrypsin M variant allele, Mwhitsable: implications for DNA-based diagnosis. Diagn. Mol Pathol 8: 205-10
