A novel diagnostic algorithm may be more accurate and cost-effective for patients with suspected alpha-1 antitrypsin deficiency (AATD), according to a study recently published in Medicina Clínica.
The “La Palma” diagnostic algorithm, as the authors named it, proposes to assess both alpha-1 antitrypsin (AAT) levels and genotype determination of the Pi*S and Pi*Z alleles of the SERPINA1 gene in the first visit. If neither result is abnormal, AATD may be ruled out.
On the contrary, whenever genetic testing reports the presence of either Pi*MS, Pi*SS, Pi*MZ, Pi*SZ, or Pi*ZZ, a diagnosis could be made, regardless of the AAT levels. Finally, if the genotype is not consistent with the disease but AAT levels are abnormal, isoelectric focus or sequencing can be considered to characterize AATD.
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“Other studies have shown that the sole determination of the genotype may be sufficient to reach a diagnosis of AATD without the need to perform AAT levels or follow an algorithm, however, the combined determination of levels and genotype in the same act, proved to be more profitable and successful, avoiding diagnostic delays and inconveniences for patients,” the authors wrote.
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In this prospective observational study that included 1510 patients from a pneumology clinic who underwent the proposed algorithm, the median age was 55.04 years, and the majority were males (56.1%). As expected, 54.4% had some sort of smoking history. The median AAT level was 124.08 mg/dl, and 31.4% had a genotype associated with AATD, of which Pi*MS was the most common, found in 287 (18.4%) of the individuals.
“The results showed that if we had applied the current diagnostic algorithm, and performed genetic analysis only on patients with AAT levels below the stipulated limit, the percentage of patients in whom the Pi*S and Pi*Z alleles had been detected would only be 6.49%, additionally, if we had only performed it on patients with chronic obstructive pulmonary disease, success will decrease to only 1.65%,” the authors said.
These findings further highlight the importance of a genetic diagnosis in this disease. Although AAT levels should also be determined, its diagnostic and screening value remains unclear, possibly due to its high variability among patients and even among AATD genotypes. For example, while Pi*MZ exhibits AAT levels of 66 mg/dl to 110 mg/dl, Pi*SS is usually between 75 mg/dl and 125 mg/dl, yielding a higher probability of obtaining a false negative result.
Reference
Hernández Pérez J, López Charry C. Usefulness of the “La palma” diagnostic algorithm in the alpha-1 antitrypsin deficiency. Med Clin. Published online June 24, 2022. doi:10.1016/j.medcli.2022.03.027
