Alpha 1-antitrypsin deficiency differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mazia Fatima, MBBS [2]

Overview

Alpha 1-antitrypsin deficiency has to be differentiated from other conditions with similar presentation like autoimmune hepatitis, bronchiectasis, bronchitis, chronic obstructive pulmonary disease (COPD), cystic fibrosis, emphysema, primary ciliary dyskinesia (Kartagener Syndrome), viral hepatitis.

Differentiating Alpha 1-antitrypsin deficiency from Other Diseases

Alpha 1-antitrypsin deficiency presents with symptoms of emphysema associated with compromised liver function tests and/or cirrhosis. Differential diagnosis of jaundice and RUQ pain includes:

Jaundice and RUQ pain differential diagnosis are:

Classification of jaundice based on etiology Disease History and clinical manifestations Diagnosis Lab Findings Other blood tests Other diagnostic Family history Fever RUQ Pain Pruritis Hepatomegaly AST ALT ALK BLR Indirect BLR Direct Viral serology Jaundice Hepatocellular Jaundice Hemochromatosis + - -/+ - + ↑ ↑ ↑/N ↑/N N - Ferritin ↑ Liver biopsy Wilson's disease + - -/+ - + ↑ ↑ N ↑/N N - Serum cerulloplasmin ↑ Liver biopsy Alcoholic hepatitis - -/+ -/+ - + ↑↑ ↑ N ↑/N N - - - Cirrhosis -/+ -/+ -/+ - -/+ ↑ ↑ ↑/N ↑/N ↑/N -/+ Thrombocytopenia hypotrophied liver on ultrasound Alpha 1-antitrypsin deficiency + -/+ -/+ - + ↑ ↑ ↑/N ↑/N ↑/N - Serum alpha1-antitrypsin levels decreased Hepatomegaly on CT Cholestatic Jaundice Common bile duct stone -/+ - + + -/+ N N ↑ N ↑ - Dilated ducts on sonography CT/ERCP Hepatitis A cholestatic type - -/+ + + -/+ N N ↑ N ↑ + HAV- AB Abdominal ultrasound EBV / CMV hepatitis - -/+ + + -/+ N N ↑ N ↑ + Positive serology Primary biliary cirrhosis -/+ - -/+ + -/+ N/↑ N/↑ ↑ N ↑ - AMA positive Liver biopsy Primary sclerosing cholangitis -/+ - -/+ + -/+ N/↑ N/↑ ↑ N ↑ - Beading on MRCP Liver biopsy Pancreatic carcinoma + - -/+ - -/+ N/↑ N/↑ ↑ N ↑ - Mass on ultrasound CT scan for diagnosis

The differential diagnosis of jaundice, fever, and RUQ pain are:

Classification of jaundice based on etiology Disease History and clinical manifestations Diagnosis Lab Findings Other blood tests Other diagnostic Family history Fever RUQ Pain Pruritis Hepatomegaly AST ALT ALK BLR Indirect BLR Direct Viral serology Jaundice Hepatocellular Jaundice Alcoholic hepatitis - -/+ -/+ - + ↑↑ ↑ N ↑/N N - - - Cirrhosis -/+ -/+ -/+ - -/+ ↑ ↑ ↑/N ↑/N ↑/N -/+ Thrombocytopenia Small liver on ultrasound Alpha 1-antitrypsin deficiency + -/+ -/+ - + ↑ ↑ ↑/N ↑/N ↑/N - Serum alpha1-antitrypsin levels decreased Hepatomegaly on CT Cholestatic Jaundice Hepatitis A cholestatic type - -/+ + + -/+ N N ↑ N ↑ + HAV- AB Abdominal ultrasound EBV / CMV hepatitis - -/+ + + -/+ N N ↑ N ↑ + Positive serology PCR or ELISA

Differential diagnosis of cough with wheezes is :

Diseases	Symptoms			Signs			Diagosis
	Fever	Cough	Chest pain	Wheezes	Crackles	Tachypnea	Lab tests	Imaging
Asthma	-	Dry/Productive	-	+	-	+	Lab tests to exclude other diseases. Serum examination shows elevated level of eosinophils due to allergy.	CT scan shows: Dilated bronchi. Bronchial wall thickening. Air trapping.
Bronchiolitis	+/-	Dry	-	+	+	+/-	ELISA and immunoassays may be done in case of RSV infection. Pulmonary function test to exclude other lung diseases.	CT scan shows: Intense bronchiolar mural inflammation. bronchial wall thickening. Centrilobular nodules with tree-in-bud pattern.
COPD	+	Productive	-	+	+	+	Spirometry: FEV1/FVC < 70%. Arterial blood gases: hypoxemia and hypercapnia. Sputum culture.	EKG may show: P pulmonale. right ventricular hypertrophy. Narrow QRS. CT scan is more sensitive in diagnosing COPD than X ray.
Bacterial pneumonia	+	Productive	+	+	+	+/-	Diagnosis depends on presentation and physical examination. Laboratory tests: arterial blood gases may show hypoxia and acidosis. Sputum culture.	X ray is performed to detect: pleural effusion. Inflitrates within the lungs. CT scan shows: Consolidation. Ground glass appearance.
Cystic Fibrosis	+/-	Productive	+/-	-	-	+	Cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction evidenced by : Elevated sweat chloride ≥60 mmol/L (on two occasions). Presence of two disease-causing mutations in CFTR, one from each parental allele. Abnormal nasal potential difference.	X-ray : Hyperinflation presents as: Flattening of the diaphragm. Anterior bowing of the infant sternum. Increased retrosternal air space. Generalized pulmonary overinflation. Multiple nodular densities represent mucus plugging and may present in finger-in-glove shape or as a combination of V- or Y-shaped branching and bandlike shadows. Abdominal findings include dilated multiple loops of the small bowel are seen in neonatal meconium ileus.
Emphysema	+/-	Productive	-	+	+/-	+	Arterial blood gas analysis: mild-to-moderate hypoxemia without hypercapnia that progresses to worsening hypoxemia and hypercapnia develops. Chronic hypoxemia may lead to polycythemia. Sputum is mucoid and the predominant cells are macrophages.	Chest X-ray reveals signs of emphysema include: Flattening of diaphragm. Increased retrosternal air space (see on lateral chest films). A long narrow heart shadow. Tapering vascular shadows. Hyperlucency of the lungs.
Primary Ciliary Dyskinesia (Kartagener Syndrome)	+/-	Productive	-	+	+	+	Low or absent amount of nasal nitric oxide (nNO). Mucociliary clearance may be useful for screening. Confirmation with tests of ciliary function.	Chest X-ray reveals : Bronchial wall thickening. Bronchiectasis and hyperinflation. Cystic bronchiectasis with air-fluid levels may be visible. Usually involves the lower and middle lobes.
Alpha 1-antitrypsin deficiency	+/-	Productive	-	+	+	+	Reduced concentration of serum alpha1-antitrypsin levels is diagnostic of AATD. Moderate-to-severe airflow obstruction with an FEV1. Reduced vital capacity. Increased lung volumes secondary to air trapping (residual volume >120% of predicted value) are usually present.	Chest X-ray Alpha1-antitrypsin deficiency (AATD) emphysema presents as: a hyperlucent appearance because healthy tissue has been destroyed. Affected regions also are described as oligemic because they lack the normal rich pattern of branching blood vessels. An unusual characteristic in alpha1-antitrypsin deficiency is found in about 60% of PiZZ patients is a striking basilar distribution. In contrast, cigarette smoking is associated with more severe apical disease.

AATD can present as neonatal jaundice. The differential diagnosis for neonatal jaundice is:

Etiology Of Neonatal Jaundice History and clinical manifestations Diagnosis Lab Findings Other blood tests Other diagnostic Family history Fever RUQ Pain Pruritis AST ALT ALK BLR Indirect BLR Direct Viral serology Alpha-1 antitrypsin deficiency + -/+ -/+ - ↑ ↑ N ↑ ↑ - Genetic testing Liver biopsy Breast feeding failure jaundice - - - - - - - ↑ - - - - Breast Milk Jaundice - - - - - - - ↑ - - - - Crigler-Najjar type 2 + - - - N N N ↑ ↑ - Genetic testing Gilbert Syndrome + - - - N N N ↑ ↑ - Genetic testing Rotor syndrome + - - - N N N N ↑ - Genetic testing Liver biopsy Dubin-Johnson syndrome + - - - N N N N ↑ - Genetic testing Liver biopsy Hereditory spherocytosis + - -/+ - N N N ↑ N - Genetic testing Osmotic fragility G6PD deficiency + - - - N N N ↑ N - Genetic testing Thalassemia + - - - N N N ↑ N - Genetic testing Sickle cell disease + - - - N N N ↑ N - Genetic testing Immune hemolysis - -/+ - - N N N ↑ N - Autoantibodies

References

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