Alpha₁-Antitrypsin Phenotype: Transient Cathodal Shift in Serum of Infant Girl with Urinary Cytomegalovirus and Fatty Liver

Abstract

Summary: A 2-month-old white girl had severe liver disease (but without signs of hepatic necrosis, infection or cirrhosis), urinary cytomegalovirus, transient reduction of α₁-antitrypsin concentration and transient abnormal α₁-antitrypsin phenotype that were not present in her parents. Five serum specimens that were obtained during the 1½ months of acute phase liver disease indicated, by polyacrylamide gel isoelectric focusing (PAG-IEF), acid starch gel and agarose electrophoresis as well as immunofixation, an unusual α₁-antitrypsin phenotype that we labeled delta (Δ). It migrated adjacent to Z, i.e., cathodal of Z and Zpratt on PAG-IEF; anodal of Z but cathodal of X, S, Zpratt on starch gel. We labeled the girl's complete phenotype MΔ. After clinical recovery, her phenotype was MM and identical to that of her parents. Hepatic electron-microscopy of the acute phase specimen showed dilated bile canaliculi. We observed the following in hepatocytes: clusters of globular inclusions surrounded by myelin sheets that, to a lesser extent, also appeared in the liver of CMV-infected children with phenotype MM; dilated endoplasmic reticulum cisternae that contained floccular material; and marked steatosis. These changes were less severe in the convalescent liver specimen.

Speculation: The patient's transient α₁-antitrypsin Δ protein may be the result of a postribosomal reduction in sialic acid of M protein triggered perhaps by sever liver disease. If so, we would not expect a further cathodal shift of Pi type Δ after treatment of MΔ serum with neuraminidase. Alternatively, Δ protein might be the product of an α₁-antitrypsin allele Pi^Δ that was transiently activated by the stress of the liver disease as is the juvenile globin gene in the adult goat by erythropoietic stress. The argument for Pi^Δ would be strengthened if: (1) the identical Δ protein was found in patients with other severe diseases of the liver; (2) the primary structure of Δ protein differed from that of M protein; (3) the material within the cisternae of the patient's hepatocytes was related to α₁-anti-trypsin; and (4) neuraminidase treatment of MΔ serum was followed by a further cathodal shift of Pi type Δ.

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