From the Guidelines
I strongly recommend genetic counseling and regular monitoring of lung and liver health for patients with an alpha-1 antitrypsin (A1AT) test result showing a phenotype of MZ. The MZ phenotype indicates that the patient is a carrier of one normal M allele and one deficient Z allele for alpha-1 antitrypsin, resulting in approximately 60% of normal AAT protein levels 1. This carrier state poses a slightly increased risk of developing emphysema, particularly if the patient smokes or has other environmental exposures. Key considerations for management include:
- Complete avoidance of smoking
- Minimization of exposure to occupational and environmental pollutants
- Regular pulmonary function tests to monitor lung health
- Periodic assessment of liver function due to a small increased risk of liver disease
- Consideration of testing for family members, as this is a genetic condition
- Early intervention with bronchodilators and standard COPD management if respiratory symptoms develop. It's essential to note that the MZ phenotype itself does not typically require augmentation therapy, which is reserved for severe deficiency states, such as the ZZ phenotype 1.
From the Research
Implications of an MZ Phenotype
An alpha-1 antitrypsin (A1AT) test result showing a phenotype of MZ has several implications:
- The individual has an intermediate deficiency of A1AT, which may increase the risk of lung disease, particularly in smokers 2, 3.
- The risk of emphysema is more pronounced in MZ smokers, especially when combined with other environmental challenges 2.
- Augmentation therapy is not supported by objective studies for MZ individuals 4, 2.
- The risk of lung disease in MZ individuals is comparable to that of SZ-AATD, but not as high as ZZ-AATD 5.
- Some studies suggest that MZ phenotype alone may not carry a greater risk of developing lung disease than the M phenotype 3.
- However, there have been cases reported where MZ individuals have developed lung disease, such as apical lung bullae and spontaneous pneumothorax, particularly in combination with smoking 6.
Clinical Considerations
- Smoking cessation and elimination of other risk factors for lung disease are crucial for MZ individuals 4.
- Careful monitoring of lung function and consideration of environmental exposures are important for MZ individuals 2.
- The decision to prescribe augmentation therapy should be made with caution and based on individual patient factors, as there is limited evidence to support its use in MZ individuals 4, 2.