Alpha-1 Antitrypsin Deficiency
Description
● Introduction:
•AAT deficiency is a genetically inherited disorder.
•Caused by mutations in SERPINA1 gene → defective/low levels of AAT protein.
•AAT normally protects lungs from neutrophil elastase.
•Deficiency → lung damage (emphysema, bronchiectasis) + liver disease (due to protein accumulation).
➣Onset: 20–50 years.
•Smoking accelerates lung function decline.
➣Etiology & Genetics
•Inherited in autosomal codominant pattern.
•SERPINA1 gene on chromosome 14.
•150 alleles exist; M = normal.
•S allele = moderately low AAT.
•Z allele = severely low AAT.
➣Genotypes:
•MM = normal
•ZZ = severe deficiency
•SZ = risk (esp. with smoking)
•MZ = slightly increased risk
➣Phenotypes
• MM → normal (normal levels).
• Deficient → ZZ genotype frequent; AAT <35% normal.
• Null alleles result in severe lung illness, no liver damage, and no detectable AAT.
• Dysfunctional alleles result in proteins that are produced but not functional (PI*F variation, for example).
➣ Epidemiology
• Number of cases: 1 in 2,000–6,000.
• Rare in Asians; more prevalent in those with European heritage.
• 80,000–100,000 in the United States are seriously lacking.
• Over 3 million serious cases worldwide.
• frequently misdiagnosed.
●Pathophysiology
• Lungs are shielded against neutrophil elastase by AAT.
• Emphysema results from a deficiency in elastase, which kills alveoli.
• Misfolded AAT leads to hepatotoxic stress through liver accumulation.
• Smoking, dust, chemicals, and infections are examples of environmental variables that exacerbate illness.
• Emphysema risk factors include dust, smoking, a family history of COPD, and asthma or bronchitis.
• ZZ genotype is most affected by liver cirrhosis.
• Viral hepatitis has less of an effect on fibrosis, but alcohol exacerbates it.
➣ Clinical Characteristics (Physical & History)
• Affected organs include the skin, liver, and lungs.
• Pulmonary: dyspnoea, cough, sputum, wheezing, pneumothorax, bronchiectasis, early-onset •COPD/emphysema, and basilar-predominant emphysema.
• Liver: cirrhosis, hepatocellular cancer, and hepatitis
• Skin: plaques, nodules, and necrotising panniculitis.
• Additional symptoms include glomerulonephritis, aneurysms, psoriasis, urticaria, angioedema, IBD, neuropathy, and vasculitis.
●Evaluation Screening Indications:
➣ Young, nonsmoking people with COPD and basilar emphysema
➣ Inexplicable liver illness
➣ Asthma that is not responsive
➣ Vasculitis, panniculitis, and bronchiectasis
➣ Tests: Levels of serum AAT (less than 11 μmol/L indicates a severe deficit)
• Genotyping (alleles S, Z, I, and F)
• The gold standard phenotypic test is isoelectric focussing.
• Tests for pulmonary function (DLCO, spirometry)
• CT/X-ray of the chest (bullae, basilar emphysema)
• Ultrasound and liver function testing
• Monitoring includes yearly liver function, cirrhosis imaging, and spirometry 6–12 months.
Protocol
●Management
• Lifestyle: restrict alcohol intake, avoid dust, stop smoking, and be vaccinated against hepatitis A/B, influenza, and pneumococcal disease.
• Bronchodilators, steroids, oxygen if saturation is less than 88%, pulmonary rehabilitation, and nutrition are all part of pulmonary therapy.
• IV pooled plasma AAT is an augmentation treatment that has been FDA-approved since 1987.
• AAT <11 μmol/L, FEV1 <80%, nonsmoker, ≥18 years old are indications.
• Not for smokers, isolated liver disease, or heterozygotes.
• Side effects include rare anaphylaxis and mild flu-like symptoms.
• For extreme situations, lung transplantation may be necessary.
➣Major Problems Faced
• Early-onset emphysema, COPD, bronchiectasis, pneumothorax, persistent cough, and dyspnoea are examples of progressive pulmonary problems.
• Hepatitis, cirrhosis, and hepatocellular cancer are all examples of liver disease brought on by an accumulation of aberrant proteins.
• Skin (rare): vasculitis, nodules, necrotising panniculitis, and other systemic symptoms.
• complications brought on by environmental exposures (dust, smoke) and infections.
● Strategies for Management
• Lifestyle change: Avoiding dust and chemicals at work and in the surroundings; completely quitting smoking is essential for delaying lung deterioration.
• Vaccination: Hepatitis A and B for liver protection, as well as annual pneumococcal and influenza vaccinations.
• Pharmacotherapy: glucocorticoids and inhaled bronchodilators to treat the symptoms of COPD.
• IV pooled human alpha-1 antitrypsin for disease-specific augmentation treatment in qualified patients with significant lung involvement.
• exacerbation management in accordance with COPD recommendations.
• Liver transplantation: for cirrhosis or severe liver disease.
➣ Distinctive Diagnosis
• Emphysema, chronic bronchitis, and bronchiectasis are examples of lung diseases.
• Hemochromatosis, Wilson disease, NAFLD/NASH, primary biliary cirrhosis, and chronic viral hepatitis are examples of liver diseases.
➣Prevention & Patient Education
• Stop smoking, stay away from chemicals and dust.
• Pneumococcal and flu shots every year.
• Avoiding or limiting alcohol use.
• immunisation against hepatitis A and B.
• Testing and genetic counselling for first-degree relatives.
➣Complications Pulmonary: COPD, emphysema, asthma, chronic bronchitis.
• Hepatic: hepatocellular carcinoma, cirrhosis.
• Skin conditions: panniculitis.
➣Monitoring and Surveillance: Regular pulmonary function testing 6-minute walks and evaluations of quality of life every six to twelve months.
Abdominal ultrasonography and liver function assessment are done annually to monitor for cancer and liver disease.
Advanced Therapies and Surgery:
oxygen supplementation at home for long-term hypoxaemia.
transplanting lungs in cases of severe respiratory insufficiency.
liver transplantation for cirrhosis or end-stage liver disease.
Genetic counselling: Identifying at-risk individuals via testing and counselling for family members.
Comprehensive Nursing Interventions
Regular monitoring of respiratory status, including oxygen saturation, dyspnoea scale, and bronchodilator responsiveness, is part of respiratory care.
oxygen and inhaler administration, as well as instruction on proper inhaler technique.
encouraging adherence to vaccinations and good hand cleanliness to prevent illness.
Supportive care: Promoting participation in pulmonary rehabilitation courses to improve self-management and exercise tolerance nutritional assistance to prevent muscular atrophy and enhance general health, particularly in patients with severe COPD.
Psychosocial support: Encouraging emotional support and referrals to support groups in order to address anxiety, depression, and coping mechanisms associated with chronic illness.
teaching about the course of the disease, how to report its symptoms, and its implications.
Liver care includes liver function testing, monitoring for symptoms of liver failure (such as jaundice and ascites), and reiterating alcohol restriction.
keeping an eye out for negative medication responses, particularly those related to IV augmentation treatment (fever, allergic reactions).
Preventing complications includes lowering the risk of falls, evaluating the skin of patients with advanced illness or impaired mobility, and identifying and treating necrotising panniculitis early.
monitoring for severe flare-ups and prompt treatment escalation in the event of hepatic or respiratory decompensation
Notes
For more details visit https://www.ncbi.nlm.nih.gov/books/NBK442030/
