nemoci-sympt/PLICNI/alfa-1-antitrypsinova-deficience/diagnostika
Bronchodilator responsiveness
- Post-bronchodilator forced expiratory volume in one second [FEV1] rise of 200 mL and 12% is common [1]
Chest computed tomography (CT) scans
- For initial assessment [1]
Diagnosis of severe AAT deficiency
- Confirmed by combination
- Demonstrating a serum level below 11 micromols/L
- Cca 57 mg/dL by nephelometry
- Testing for the most common deficient alleles (i.e., S, Z, I, F) [1]
- AAT serum level
- Greater than 20 micromol/L (80 mg/dL)
- Unlikely that the patient has clinically significant AAT deficiency [1]
Enzyme-linked-immuno-sorbent-assays in vitro
Genetic test for AAT deficiency
- Spirometry with persistent airflow obstruction
- Should be tested for AAT deficiency
- Mainly those from geographic areas with a high prevalence of AAT deficiency.
- Additional features that should lead clinicians to test:
- Emphysema in
- Young individual (e.g., age 45 years or older).
- Nonsmoker or minimal smoker
- With predominant basilar changes on the chest radiograph [1]
- Family history of emphysema and/or liver disease
- Clinical findings or history of
- Panniculitis
- Unexplained chronic liver disease [1]
Genotyping
- Necessary to identify heterozygotes and mutations that have incomplete penetrance [1]
Genotyping of the protease inhibitor (Pi) locus
- Performed on a blood sample
- Using PCR technology or restriction fragment length polymorphisms
- Detect the most common known variants (F, I, S, Z)
Gene sequencing of exonic DNA
- Can be used if both tests fail to determine the genetic variant
Isoelectric focusing (IEF)
- Gold standard blood test for identifying AAT variants
- Considered a phenotype test [1]
- In the pH range 4.5-5.5
- protein migrates in a gel according to its isoelectric point or charge in a pH gradient
- Normal A1AT is termed M
- Migrates toward the center of such an IEF gel
- Other variants are less functional
- Termed A-L and N-Z
- Dependent on whether they run proximal or distal to the M band
- The presence of deviant bands on IEF
- Can signify the presence of alpha-1 antitrypsin deficiency
- Number of identified mutations
- Exceeded the number of letters in the alphabet
- Subscripts have been added to most recent discoveries in this area [2]
- Heterozygote with two different copies of the gene
- May have two different bands showing on electrofocusing
- Heterozygote with one null mutant
- Abolishes expression of the gene
- Will only show one band [2]
Liver guidelines
- Are lacking regarding monitoring for liver disease in patients
- Homozygous for PiZ
- PiS[iiyama]
- PiM[malton]
- It is advised on an annual basis to assess
- Serum aminotransferases
- Alkaline phosphatase
- bilirubin
- Some clinicians also obtain a complete blood count (CBC)
- Thrombocytopenia
- Abdominal ultrasound looking for cirrhosis every 6 to 12 months [1]
Monitoring asymptomatic patients
- Those with no respiratory symptoms and a normal baseline spirometry
- FEV1 80% or greater of predicted
- Spirometry should be repeated when
- Symptoms change
- At 6 to 12-month intervals
- Unexplained decrease in the post-bronchodilator FEV1 to less than 80 predicted
- Indication to initiate augmentation therapy [1]
Protein electrophoresis
- Does not completely distinguish between A1AT and other minor proteins at the alpha-1 position (agarose gel)
- Antitrypsin can be more directly and specifically measured using a
- Nephelometric or
- Immunoturbidimetric method
- Useful for screening and identifying individuals likely to have a deficiency [2]
Pulmonary function testing
- Assess the presence and severity of lung disease
- Typically obtain
- Spirometry before and after bronchodilator
- Lung volumes
- Diffusing capacity for carbon monoxide (DLCO) [1]
- If DLCO is below normal or if the patient reports exertional dyspnea
6-minute walk test
- Should be obtained [1]
FEV1
- Major determinant of survival in AAT-deficient individuals
- Mortality rising considerably as FEV1 falls below 35% of predicted [3]
