Are you an Alpha too?  Join our Facebook group!   A1ADSupport


Risk of lung and liver disease for MZs

People with the MZ genotype do not have severe AATD but are genetic carriers of the Z mutation. The Z mutation is a deficiency allele (version of the gene) that reduces the quantity of alpha-1 antitrypsin (AAT) in the blood, and causes AATD in people with two mutations (e.g. ZZ, SZ). The MZ genotype is not associated with an increased risk for lung disease in nonsmokers. Higher risk is seen in MZ individuals who smoke. A slightly increased risk for liver disease has been seen in MZ populations.

Because Alpha-1 is a genetic condition, your result means that your relatives are at increased risk to also have abnormal alpha-1 genes. We encourage you to make your family members and any reproductive partner aware of your result and the availability of testing. Reproductive partners of people with abnormal alpha-1 genes should be offered testing to assess risk to children.

Alpha-1 at MUSC – Genetic Counseling

• 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)

The management of individuals with the PI*MZ genotype, characterized by mild or moderate AAT deficiency, is less clear than of those with the most common severe deficiency genotype (PI*ZZ). Recent genetic data suggest that the PI*MZ genotype may be significantly more prevalent than currently thought. The only specific treatment for lung disease associated with severe AATD is the intravenous infusion of AAT augmentation therapy, which has been shown to slow disease progression in PI*ZZ individuals. There is no specific evidence for the clinical benefit of AAT therapy in PI*MZ individuals, and the risk of emphysema development in this group remains controversial. As such, current guidelines do not support the use of AAT augmentation in PI*MZ individuals.

Alpha-1 antitrypsin (AAT) augmentation therapy in individuals with the PI*MZ genotype: a pro/con debate on a working hypothesisBMC Pulmonary Medicine

The use of IV augmentation therapy with plasma-derived alpha1-antitrypsin (AAT) has become the standard of care for the treatment of pulmonary disease associated with the severe genetic deficiency of AAT. The Medical and Scientific Advisory Committee of the Alpha-1 Foundation has become aware that physicians are prescribing this expensive blood product for the treatment of individuals with a single abnormal AAT gene, primarily the PIMZ genotype. We are aware of no evidence that such therapy is effective in this patient population. The most important therapeutic interventions in such patients remain smoking cessation and elimination of other risk factors for lung disease. This commentary discusses the treatment of AAT deficiency and the concerns regarding treatment of PIMZ individuals. We conclude that clinicians should avoid prescribing augmentation therapy for this heterozygote population.

alpha1-Antitrypsin augmentation therapy for PI*MZ heterozygotes: a cautionary note National Library of Medicine