What is the Pratt MZ (M and N blood group system) phenotype?

What is the MZ Phenotype in Alpha-1 Antitrypsin Deficiency?

The MZ phenotype refers to heterozygous alpha-1 antitrypsin (AAT) deficiency where an individual inherits one normal M allele and one deficient Z allele, resulting in AAT plasma levels approximately 60% of normal (around 50-60 mg/dL reduction compared to MM phenotype). 1, 2

Genetic and Biochemical Characteristics

• The MZ phenotype represents a codominant inheritance pattern at the SERPINA1 gene locus, where both the M and Z alleles are expressed 2
• Individuals with MZ phenotype have significantly reduced AAT levels compared to normal MM individuals, with a mean difference of approximately 52 mg/dL lower 1
• This intermediate deficiency state places AAT levels at roughly 60% of the normal MM phenotype concentration 2

Clinical Significance and Disease Risk

The MZ phenotype is considered a predisposition rather than a disease itself, conferring increased but modest risk for lung and liver disease under specific conditions. 2

Lung Disease Risk

• MZ individuals have a relative risk of 2.2 for COPD-related hospitalization compared to the general population 2
• Cigarette smoking dramatically amplifies risk, with MZ smokers showing odds ratios of 2.8 for rapid FEV1 decline 1
• The combination of MZ genotype with family history of COPD increases risk substantially (OR 9.7) 1
• Environmental and occupational exposures (dust, gases, fumes) further increase susceptibility to obstructive lung disease 1, 2

Liver Disease Risk

• Multiple studies demonstrate increased risk for chronic liver disease (CLD) in MZ heterozygotes, with odds ratios ranging from 1.8 to 3.1 across large case series 1
• The risk of developing cirrhosis for MZ individuals aged 18-50 is estimated at 2-5%, increasing with age particularly in never-smokers over 50 2
• Cryptogenic cirrhosis shows particular overrepresentation of MZ phenotype, with prevalence of 20.5-21% in cryptogenic cases compared to only 2.6-3.5% in other cirrhosis types 1
• Hepatitis C infection may act as an additive risk factor, though data remain controversial 1
• Alcohol abuse shows conflicting evidence as a cofactor, with most studies not supporting a strong association 1
• No association exists between MZ phenotype and autoimmune liver disease or hepatitis B-related cirrhosis 1

Diagnostic Considerations

• AAT behaves as an acute phase reactant, meaning levels can rise during inflammation, potentially masking underlying deficiency in MZ individuals 3
• During acute illness, MZ patients may show falsely normal or even elevated AAT levels (up to 1.4 g/L) 3
• Testing should be avoided during acute illness; if suspicion remains high despite normal levels, proceed directly to DNA sequencing of SERPINA1 3
• Confirmation requires qualitative phenotyping or genotyping, not just quantitative AAT measurement 2

Management Recommendations

MZ individuals without risk factors do not require specialized monitoring beyond routine health maintenance. 2

For Asymptomatic MZ Without Risk Factors:

• Clinical evaluation every 1-2 years 2
• Liver function tests every 1-2 years 2
• Pulmonary function tests every 3-5 years 2

For MZ With Risk Factors (smoking, occupational exposures, abnormal LFTs):

• More frequent clinical evaluations 2
• Annual pulmonary function tests 2
• Annual liver function tests 2

Essential Preventive Measures:

• Smoking cessation is the single most important intervention 2
• Avoidance of environmental irritants and occupational exposures 2
• Maintain current vaccination status 2
• Consider testing first-degree relatives 2

Common Pitfalls to Avoid

• Do not rely solely on AAT levels during acute illness or inflammatory states, as falsely normal results may occur 3
• Do not assume MZ phenotype is benign—it requires risk stratification based on smoking history and environmental exposures 1, 2
• Do not overlook cryptogenic cirrhosis as a potential manifestation of MZ phenotype, particularly in males 1
• Early studies using PAS-D staining underestimated MZ prevalence by approximately 20%, so modern phenotyping or genotyping methods are preferred 1

Note: This answer addresses the MZ phenotype in alpha-1 antitrypsin deficiency, not the MN blood group system mentioned in the expanded question context, as all provided evidence relates to AAT deficiency.