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[Alpha-antitrypsin deficiency in infancy]
Insights
Alpha1-antitrypsin deficiency in infants presents as neonatal biliary stasis. Liver cells accumulate abnormal alpha1-antitrypsin protein aggregates, indicating a genetic liver disease.
Area of Science:
- Hepatology
- Genetics
- Immunology
Context:
- Alpha1-antitrypsin deficiency (AATD) is a genetic disorder.
- Neonatal cholestasis can be a manifestation of AATD.
- Liver disease progression in AATD varies significantly.
Purpose:
- To investigate the clinical, histological, and genetic features of alpha1-antitrypsin deficiency in two infants.
- To characterize the ultrastructural and immunohistochemical findings of liver pathology in neonatal AATD.
- To confirm the genetic basis and inheritance pattern of AATD in affected families.
Summary:
- Two infants with protease inhibitor (Pi) ZZ phenotype presented with neonatal biliary stasis.
- Liver biopsies showed cytoplasmic inclusions positive for alpha1-antitrypsin within the endoplasmic reticulum.
- Histological and genetic studies confirmed autosomal co-dominant inheritance of the PiZ gene.
Impact:
- This study highlights the importance of considering AATD in neonatal cholestasis.
- Understanding the cellular mechanisms of AATD provides insights into protein misfolding diseases.
- Early identification and genetic counseling are crucial for families affected by AATD.
Abstract:
Clinical, histological (including electron-microscopic), immunohistochemical and genetic studies were performed on two infants with alpha1-antitrypsin deficiency. The clinical picture was one of neonatal biliary stasis. Liver biopsies revealed multiple cytoplasmic acidophilic bodies within many cells of the liver parenchyma which were strongly periodic acid-Schiff-positive, diastase-resistant and stained selectively with fluorescein-labelled rabbit antihuman alpha1-antitrypsin. Ultrastructurally, the bodies were situated within enlarged cisterns of the endoplasmatic reticulum. Both infants were of the protease inhibitor (Pi) phenotype ZZ, having inherited on PiZ gene from each parent. Results of Pi typing of both families were consistent with an autosomal co-dominant inheritance. Both infants are clinically well except for slight hepatomegaly at one year of age. But transaminase and gamma-glutamyl transpeptidase activities have remained elevated.