title: Neonatal hemochromatosis: diagnostic work-up based on a series of 56 cases of fetal death and neonatal liver failure.
abstract: OBJECTIVE
  To define an algorithm to improve diagnosis of neonatal hemochromatosis (NH) related to gestational alloimmune liver disease (GALD), which is diagnosed by immunohistochemistry demonstrating activated complement at hepatocytes (IDACH).
  
  
  METHODS
  We assessed 56 instances of fetal death or neonatal liver failure (NLF; 2006-2009), 29 (7 stillborns, 22 NLF) with NH, and 27 (5 stillborns, 22 NLF) without NH (non-NH). Immunohistochemistry was retrospectively performed in 21 cases. Cases were grouped as follows: (1) GALD as demonstrated by IDACH (n = 17); (2) indeterminate for GALD (n = 28); or (3) alternate diagnosis found (n = 11). We compared cases of immunohistochemically proven GALD with those with an alternate diagnosis.
  
  
  RESULTS
  Of the 12 stillborns, 7 had NH because of GALD (NH-GALD), one was undeterminate, and 4 had alternate diagnoses (GALD excluded). Of the 22 newborns with NH, 6 had NH-GALD, one had mitochondrial respiratory chain disorder (MRCD), and 15 were indeterminate for GALD. Of 22 non-NH newborns, extrahepatic siderosis (EHS) was not assessed in 13 (3 GALD, 1 alternate diagnosis [MRCD] and 9 indeterminate GALD) and excluded in 9 (5 alternate diagnoses and 4 indeterminate GALD). The only clinical features found to be associated with GALD were intrafamilial recurrence, prematurity, and EHS.
  
  
  CONCLUSIONS
  In unexplained fetal death or NLF, the diagnosis of subsets of NH requires tissue analysis (autopsy) to assess EHS. In patients with NH, if MRCD is ruled out, NH-GALD is likely. The rate of IDACH in the diagnosis of GALD in cases without NH requires further study.
authors.affiliation: Department of Pediatric Gastroenterology and Hepatology, Hôpital Femme Mère Enfant, Hospices Civils de Lyon et Université Lyon 1, Lyon, France. Electronic address: sophie.heissat@chu-lyon.fr.
authors.forename: Sophie
authors.initials: S
authors.lastname: Heissat
authors.affiliation: Department of Pathology, Hôpital Femme Mère Enfant, Hospices Civils de Lyon et Université Lyon 1, Lyon, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Collardeau-Frachon
authors.affiliation: Department of Pediatric Hepatology and Metabolic Diseases, CHU Toulouse, Toulouse, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Baruteau
authors.affiliation: Department of Pathology, Hôpital Femme Mère Enfant, Hospices Civils de Lyon et Université Lyon 1, Lyon, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Dubruc
authors.affiliation: Department of Pathology, Hôpital Femme Mère Enfant, Hospices Civils de Lyon et Université Lyon 1, Lyon, France.
authors.forename: Raymonde
authors.initials: R
authors.lastname: Bouvier
authors.affiliation: Department of Pathology, Villejuif, France.
authors.forename: Monique
authors.initials: M
authors.lastname: Fabre
authors.affiliation: Department of Genetics, Hôpital Femme-Mère-Enfant, HCL Lyon, Lyon, France.
authors.forename: Marie Pierre
authors.initials: MP
authors.lastname: Cordier
authors.affiliation: Department of Pediatric Hepatology and Metabolic Diseases, CHU Toulouse, Toulouse, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Broué
authors.affiliation: Department of Pediatrics, Hôpital Mère et Enfant, CHU Limoges, Limoges, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Guigonis
authors.affiliation: Medical-Surgical Center, Hepatology, and Transplantation AP-HP, Hôpital Necker Enfants Malades, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Debray
mesh_terms: D001344:Autopsy; D005260:Female; D005313:Fetal Death / Q000209:etiology*; D005333:Fetus; D005602:France; D006432:Hemochromatosis / Q000150:complications / Q000175:diagnosis*; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D017093:Liver Failure / Q000209:etiology* / Q000378:metabolism; D008297:Male; D010375:Pedigree; D011247:Pregnancy; D012189:Retrospective Studies; D050497:Stillbirth