O-42 COSTA RICA NATIONAL NEWBORN SCREENING LABORATORY´S EXPERIENCE IN DIAGNOSING ALPHA-1 ANTITRYPSIN DEFICIENCY

Introduction and Objectives

Alpha-1 antitrypsin (AAT) is an acute-phase glycoprotein encoded by the SERPINA1 gene. This allele has a codominant expression and Alpha-1 antitrypsin deficiency (AATD) is caused by the inheritance of two affected alleles. The spectrum of the disease depends on the variants and environmental and biological factors. This study aimed to divulge Costa Rica's experience in diagnosing AATD using biochemical and molecular approaches in patients referred to this center between 2014 and 2021.

Materials and Methods

: Forty-three patients (20 males and 23 females) were analyzed.

Biochemical parameters

Serum AAT concentrations were quantified by turbidometry (SPIN200E, ®SPINREACT). Protein electrophoresis and phenotyping isoelectric electrophoresis were performed on the HYDRASYS 2 SCAN FOCUSING (SEBIA).

Genetic characterization

Sanger sequencing of the SERPINA1 coding regions (NM_000295.5) was performed in 16 patients with rare electrophoretic patterns or MM phenotype with low AAT concentration.

Results

In 43 probands, we found an AAT mean value of 60.7mg/dl and eight different electrophoretic patterns. Most of our affected patients had an MZ or ZZ phenotype. Table 1 shows the main phenotypes and genotypes of our patients (N=25 patients); how some of them share the same electrophoretic pattern; and finally, the correlation between clinical severity and the biochemical phenotype. Our lab found two variants, one related to null phenotype and the other with uncertain clinical significance (VUS).

Conclusions

:

• This laboratory has developed an efficient and comprehensive algorithm diagnosis for AATD that involves biochemical and molecular tools.

• Genetic analysis has allowed the identification of null variants (Q0Cork and Q0Lisbon).

• AATD affects children and adults, with a broad severity spectrum and different clinical presentations.

• Patients with one affected allele (e.g., PI*MZ, Pi*MS) might show some clinical manifestations.

• Accurate diagnosis is essential for optimal clinical attention and to reduce the diagnostic odyssey.

Table 1. Description of main probands phenotypes and genotypes in 25 of our patients

* Only in 16 patients genotype was analyzed

N/A: not analyzed.

WT: Wild type.