Differential Diagnosis
Lung Disease Differential diagnoses include disorders causing chronic obstructive pulmonary disease (COPD), such as emphysema, chronic bronchitis, and bronchiectasis. have described an autosomal dominant predisposition to emphysema in a single large French Canadian family that affects the protein, tyrosine phosphatase non-receptor, type 6 (PTPN6). As with severe deficiency of AAT, in this newly described condition there is near-complete penetrance for emphysema that is lower-lobe predominant and can be early onset (i.e., 4th-5th decade). Unlike alpha-1 antitrypsin deficiency (AATD), PTPN6-type emphysema is inherited as an autosomal dominant condition. Liver Disease See for genetic disorders to consider in the differential diagnosis of AATD-related liver disease. The differential diagnosis of neonatal cholestasis also includes multiple metabolic diseases and other non-hereditary diseases including extrahepatic biliary atresia and gestational alloimmune liver disease (formerly known as neonatal hemochromatosis). Acquired disorders to consider include chronic viral hepatitis, alcoholic and non-alcoholic steatohepatitis, sclerosing cholangitis, and primary biliary cholangitis. Table 5. Genetic Disorders Associated with Liver Disease in the Differential Diagnosis of Alpha-1 Antitrypsin Deficiency
Gene(s) | Disorder | MOI | Clinical Features of Differential Diagnosis Disorder |
|---|
TJP2 | Progressive familial intrahepatic cholestasis (PFIC) (See OMIM PS211600 ATPB1 Deficiency.) | AR | Cholestasis can be prominent; presentation in infancy is common.; Risk for hepatocellular carcinoma in PFIC2 AATD is higher than in other liver diseases.; Other extrahepatic manifestations may incl hearing loss, diarrhea, pancreatitis, failure to thrive, fat-soluble vitamin deficiencies. |
ABCC2 | Dubin-Johnson syndrome (OMIM 237500) | AR | Jaundice in infancy w/both direct indirect hyperbilirubinemia |
Wilson disease | AR | Chronic liver disease | May be accompanied by neurologic /or psychiatric symptoms; Kayser-Fleischer rings in 50% of those w/hepatic disease; serum ceruloplasmin urinary copper excretion; Acute liver failure is assoc w/hemolysis serum alkaline phosphatase.; Liver biopsy shows excess copper accumulation steatosis. CFTR |
Cystic fibrosis | AR | Cholestasis in infancy; Liver disease can become more apparent in older children. | Extrahepatic obstruction due to inspissated bile or bile plugs HAMP HJV |
Juvenile hereditary hemochromatosis | AR | Presentation can be in early childhood ado... | — |
Source: GeneReviews — "Alpha-1 Antitrypsin Deficiency"
