Alpha-1 antitrypsin deficiency is a rare inherited disease
The AAT gene consists of two alleles, which are passed from parent to child by simple, autosomal, and codominant Mendelian inheritance.
Each child receives an allele from each of its parents. Normal alleles, present in 85-90% of individuals, are called M, and therefore a normal individual receives two M alleles (one from each parent), which form an MM genotype.
The most frequent deficient alleles are called S and Z, and are found in 10% and 2% of the Spanish population, respectively. Alleles M, S, and Z respectively express about 100%, 40%, and 15% AAT.
In accordance with the foregoing, the vast majority of phenotypes found in practice are combinations of M, S and Z, that is: MM (normal genotype, exhibited by around 85% of Spaniards of Caucasian race), MS, SS, MZ, SZ and ZZ (5 deficient genotypes, found in the remaining 15% of Spaniards).
The human genotype
MM genotypes express 100% AAT in blood, while MS, SS, MZ, SZ and ZZ express (roughly) 80%, 60%, 55%, 40% and 15%, respectively.
Characteristics of Alpha-1 Antitrypsin
LAAT is a multifunctional protein, with multiple protease inhibitory properties and non-inhibitory qualities, which provide the human body with remarkable anti-inflammatory, immunomodulatory, anti-microbial and tissue repair capabilities.
Severe AAT deficiency, defined by serum AAT levels below 35% of the expected mean value, or 60 mg / dL (measured by nephelometry), or 80 mg / dL (if the measurement is made by radial immunodiffusion, a technique in disuse) is an infrequent condition, generally related to ZZ genotypes, and much less frequently with various combinations of Z, S, rare and null alleles.
In fact, in clinical practice, 96% of the pathologies associated with AAT deficiency occur in homozygous ZZ, and the remaining 4% in heterozygous SZ, MZ and in the extremely infrequent rare and null genotypes.
Assumptions of transmission of the AAT gene
Both parents have MM genotypes; consequently, all their descendants inherit MM genotypes.
Both parents are MZ; in this case, the offspring have a 25% chance of receiving an MM genotype, a 50% chance of inheriting an MZ, and a 25% chance of receiving a ZZ genotype.
One parent is MZ and the other is MS; children can receive a MM (25%), MS (25%), MZ (25%), or SZ (25%) genotype.
One parent is a carrier of an MZ genotype and the other of an SZ; children can inherit MS (25%), MZ (25%), SZ (25%), or ZZ (25%) genotypes.Both parents have MM genotypes; consequently, all their descendants inherit MM genotypes.