Alpha1-Antitrypsin Deficiency in Children

Introduction to Alpha1-Antitrypsin Deficiency in Children

Alpha1-Antitrypsin Deficiency (A1ATD) is a genetic disorder characterized by low levels of alpha1-antitrypsin (A1AT) protein in the blood and lungs. This condition primarily affects the lungs and liver, with potential manifestations in childhood.

Inheritance: Autosomal recessive
Gene affected: SERPINA1 (Serpin Family A Member 1)
Prevalence: Approximately 1 in 2,000 to 1 in 5,000 individuals of European descent

Pathophysiology

A1ATD results from mutations in the SERPINA1 gene, leading to reduced production or dysfunction of the A1AT protein.

Key Points:

A1AT is a serine protease inhibitor that protects tissues from neutrophil elastase
Deficiency leads to unopposed proteolytic activity in the lungs
Accumulation of abnormal A1AT in hepatocytes can cause liver damage

Common Genotypes:

MM: Normal
MZ: Carrier (heterozygous)
ZZ: Most common severe deficiency
SZ: Moderate deficiency
Null: No detectable A1AT (rare)

Clinical Manifestations in Children

Liver Manifestations:

Neonatal cholestasis (10-15% of ZZ infants)
Elevated liver enzymes
Hepatomegaly
Cirrhosis (rare in childhood)

Pulmonary Manifestations:

Usually not prominent in childhood
May include recurrent wheezing or asthma-like symptoms
Increased susceptibility to respiratory infections

Other Manifestations:

Failure to thrive
Panniculitis (rare)

Diagnosis

Screening and Initial Tests:

Serum A1AT level (normal range: 20-53 µmol/L or 150-350 mg/dL)
Liver function tests (AST, ALT, GGT, bilirubin)
Complete blood count

Confirmatory Tests:

A1AT phenotyping or genotyping
Liver biopsy (if clinically indicated)

Additional Assessments:

Pulmonary function tests (in older children)
Chest X-ray or CT scan (if respiratory symptoms present)
Abdominal ultrasound

Treatment and Management

Liver Disease Management:

Nutritional support
Fat-soluble vitamin supplementation
Ursodeoxycholic acid for cholestasis
Liver transplantation for end-stage liver disease

Pulmonary Care:

Avoidance of smoking and secondhand smoke exposure
Prompt treatment of respiratory infections
Bronchodilators and inhaled corticosteroids for asthma-like symptoms
Annual influenza vaccination

Augmentation Therapy:

Not typically used in children unless severe lung disease is present. Involves intravenous infusion of purified human A1AT.

Prognosis and Follow-up

Prognosis:

Variable, depending on genotype and organ involvement
Most children with liver involvement improve with age
Lung disease typically progresses slowly, with significant symptoms often not appearing until adulthood

Follow-up:

Regular monitoring of liver function
Annual pulmonary function tests (in older children)
Routine vaccinations, including hepatitis A and B
Genetic counseling for family members

2. Alpha1-Antitrypsin Deficiency in Children

Q: What is the primary function of alpha1-antitrypsin in the body? A: To protect tissues from neutrophil elastase
Q: Which organ is most commonly affected by alpha1-antitrypsin deficiency in children? A: The liver
Q: What is the genetic inheritance pattern of alpha1-antitrypsin deficiency? A: Autosomal co-dominant
Q: Which chromosome contains the gene responsible for alpha1-antitrypsin? A: Chromosome 14
Q: What is the most common genotype associated with severe alpha1-antitrypsin deficiency? A: PiZZ
Q: How does alpha1-antitrypsin deficiency primarily affect the lungs in children? A: By increasing susceptibility to emphysema and chronic obstructive pulmonary disease
Q: What is the primary liver manifestation of alpha1-antitrypsin deficiency in infants? A: Cholestasis
Q: Which diagnostic test is considered the gold standard for alpha1-antitrypsin deficiency? A: Genetic testing for SERPINA1 gene mutations
Q: What is the normal range of serum alpha1-antitrypsin levels? A: 20-53 μmol/L (100-220 mg/dL)
Q: Which pulmonary function test abnormality is most commonly associated with alpha1-antitrypsin deficiency in children? A: Decreased diffusion capacity
Q: What is the primary treatment for lung disease associated with alpha1-antitrypsin deficiency? A: Augmentation therapy with intravenous alpha1-antitrypsin
Q: Which environmental factor most significantly increases the risk of lung disease in children with alpha1-antitrypsin deficiency? A: Exposure to cigarette smoke
Q: What is the mechanism of liver injury in alpha1-antitrypsin deficiency? A: Accumulation of misfolded alpha1-antitrypsin protein in hepatocytes
Q: Which imaging technique is most useful for assessing liver involvement in alpha1-antitrypsin deficiency? A: Ultrasound
Q: What is the approximate prevalence of alpha1-antitrypsin deficiency in North American and European populations? A: 1 in 2,000 to 1 in 5,000
Q: Which respiratory symptom is most common in children with alpha1-antitrypsin deficiency? A: Dyspnea on exertion
Q: What is the role of ursodeoxycholic acid in the treatment of alpha1-antitrypsin deficiency? A: To improve bile flow and potentially reduce liver damage
Q: Which liver enzyme is typically elevated in children with alpha1-antitrypsin deficiency-associated liver disease? A: Alanine aminotransferase (ALT)
Q: What is the primary goal of newborn screening for alpha1-antitrypsin deficiency? A: Early detection and prevention of smoking initiation
Q: Which respiratory infection is particularly concerning in children with alpha1-antitrypsin deficiency? A: Pneumonia
Q: What is the recommended frequency of pulmonary function testing in children with alpha1-antitrypsin deficiency? A: Annually
Q: Which nutritional deficiency is common in children with advanced alpha1-antitrypsin deficiency-associated liver disease? A: Vitamin D deficiency
Q: What is the role of bronchodilators in the management of alpha1-antitrypsin deficiency? A: To relieve bronchospasm and improve airflow
Q: Which complication of alpha1-antitrypsin deficiency is more common in adults but can occur in children? A: Bronchiectasis
Q: What is the primary indication for liver transplantation in children with alpha1-antitrypsin deficiency? A: End-stage liver disease or hepatocellular carcinoma
Q: Which vaccine is particularly important for children with alpha1-antitrypsin deficiency? A: Pneumococcal vaccine
Q: What is the role of inhaled corticosteroids in the management of alpha1-antitrypsin deficiency? A: To reduce airway inflammation in patients with asthma-like symptoms
Q: Which imaging technique is most useful for assessing emphysema in children with alpha1-antitrypsin deficiency? A: High-resolution computed tomography (HRCT)
Q: What is the primary goal of pulmonary rehabilitation in children with alpha1-antitrypsin deficiency? A: To improve exercise tolerance and quality of life
Q: Which genetic variant of alpha1-antitrypsin is associated with normal protein levels but decreased function? A: PiS allele