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FZ

Your Alpha-1 genotype is FZ. This means that you have a rare form of AATD. AATD is a genetic condition that raises the risk for the development of chronic obstructive pulmonary disease (COPD) and, in some cases, liver disease. The F mutation produces a dysfunctional alpha-1 protein product. The Z mutation produces an abnormal protein product that gets trapped in the liver and reduces the level of Alpha-1 protein in the blood. The FZ genotype results in an increased risk for lung disease. Risk for liver disease is not known to be increased beyond that of an MZ carrier. We recommend that you follow-up with a physician familiar with Alpha-1 to discuss personalized screening or management recommendations. A list of Alpha-1 specialists can be found at www.alpha1.org.

Because Alpha-1 is a genetic condition, your result means that your relatives are at increased risk to also have AATD or carry abnormal alpha-1 genes. We encourage you to make your family members aware of the condition in your family and the availability of testing. In order for your relatives to have accurate testing, the test must look for both the F and Z mutations. AAT level testing is not accurate to detect Alpha-1 involving the F mutation. Reproductive partners of people with abnormal alpha-1 genes should also be offered testing to assess risk to children.

Alpha-1 at MUSC – Genetic Counseling

F: dysfunctional

  • Near normal level but doesn’t bind neutrophil elastase well
  • AAT levels may be normal in Alpha-1 involving the F
  • Likely lung risks like a Z
  • No liver accumulation
What is Your Phenotype and What Does it Mean?Kimberly Foil, MS, CGC, Genetic Counseling Program, Alpha-1 Foundation; Division of Pulmonary and Critical Care Medicine, Medical University of South Carolina (MUSC)

Z: 
• the most common clinically significant allele
• causes misfolding of antitrypsin in the liver – making normal quantities of the protein but it misfolds, gets stuck to others and forms polymers which get stuck in the liver.
• 85% trapped in the liver
• originated in Scandinavia
• estimated that 2-3% of people in North America have one copy of the Z allele

What is Your Phenotype and What Does it Mean? – Kimberly Foil, MS, CGC, Genetic Counseling Program, Alpha-1 Foundation; Division of PulmonaryMedical term referring to the lungs. and Critical Care Medicine, Medical University of South Carolina (MUSC)