title: Diagnosis of alpha-1-antitrypsin deficiency in bleeding disorder-related neonatal death.
abstract: Alpha-1-antitrypsin (AAT) deficiency is a rare genetic disorder characterized by hepatitis in neonates, childhood and adulthood (protease inhibitor (PI)*ZZ) and emphysema with or without hepatitis (PI*ZZ)/(PI*SS,SZ or null) in adulthood. We report the case of a female neonate born at 40 weeks of gestation who presented with vitamin K deficiency-related intracranial bleeding and cholestasis of which she died at 28 days of age. At autopsy, the infant was found to have intracranial bleeding, hepatomegaly, and cholestasis with paucity of bile ducts in the liver. Small periodic acid-Schiff diastase positive intrahepatic granules and positive staining with antibodies against AAT protein suggested an AAT deficiency. AAT is a glycoprotein that has a protease inhibitor function. Its deficiency can be the result of various point mutations in Serpin 1 located on chromosome 14. The diagnosis AAT deficiency was confirmed by mutation analysis showing the PI*ZZ genotype in the neonate. In conclusion, AAT deficiency is a rare genetic disorder that can lead to a serious bleeding disorder in the neonatal period if not recognised on time. Pathological diagnosis together with verifying molecular analysis can be used to identify index patients.
authors.affiliation: Department of Pathology, Radboud University Nijmegen Medical Centre, 824, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Gursah
authors.initials: G
authors.lastname: Kats-Ugurlu
authors.forename: Marije
authors.initials: M
authors.lastname: Hogeveen
authors.forename: Ann
authors.initials: A
authors.lastname: Driessen
authors.forename: Ans M W
authors.initials: AM
authors.lastname: van den Ouweland
authors.forename: Christina
authors.initials: C
authors.lastname: Hulsbergen-van de Kaa
mesh_terms: D002779:Cholestasis / Q000209:etiology; D003937:Diagnosis, Differential; D017809:Fatal Outcome; D005838:Genotype; D006529:Hepatomegaly / Q000209:etiology; D006801:Humans; D007231:Infant, Newborn; D020300:Intracranial Hemorrhages / Q000175:diagnosis / Q000209:etiology*; D008297:Male; D019896:alpha 1-Antitrypsin Deficiency / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*
references.citation: Arch Dis Child Fetal Neonatal Ed. 2009 Nov;94(6):F456-60
references.pmid: 19414430
references.citation: Nature. 1992 Jun 18;357(6379):605-7
references.pmid: 1608473
references.citation: J Pediatr Hematol Oncol. 1999 Sep-Oct;21(5):447-50
references.pmid: 10524464
references.citation: Ned Tijdschr Geneeskd. 1990 Aug 25;134(34):1642-6
references.pmid: 2215706
references.citation: Pediatr Dev Pathol. 1998 May-Jun;1(3):179-99
references.pmid: 10463278
references.citation: Orphanet J Rare Dis. 2008 Jun 19;3:16
references.pmid: 18565211
references.citation: Am J Med. 1988 Jun 24;84(6A):13-31
references.pmid: 3289385
references.citation: Clin Chem. 2006 Dec;52(12):2180-1
references.pmid: 17138849
references.citation: Am J Med. 1988 Jun 24;84(6A):3-12
references.pmid: 3289386
references.citation: Arch Dis Child. 1982 Jan;57(1):68-70
references.pmid: 6978107
references.citation: Thorax. 2004 Feb;59(2):164-9
references.pmid: 14760160
references.citation: J Perinatol. 1993 Jul-Aug;13(4):322-4
references.pmid: 8410391