Neonatal Hemochromatosis: Diagnostic Work-Up Based on a Series of 56 Cases of Fetal Death and Neonatal Liver Failure

• Published in: The Journal of pediatrics 2015, Vol.166 (1), p.66-73
• Main Authors: Heissat, Sophie, MD, Collardeau-Frachon, Sophie, MD, PhD, Baruteau, Julien, MD, Dubruc, Estelle, MD, Bouvier, Raymonde, MD, Fabre, Monique, MD, Cordier, Marie Pierre, MD, Broué, Pierre, MD, Guigonis, Vincent, MD, PhD, Debray, Dominique, MD, PhD
• Format: Article
• Language: English
• Subjects: Autopsy; Female; Fetal Death - etiology; Fetus; France; Hemochromatosis - complications; Hemochromatosis - diagnosis; Hepatocytes - metabolism; Humans; Immunohistochemistry; Infant, Newborn; Liver Failure - etiology; Liver Failure - metabolism; Male; Pediatrics; Pedigree; Pregnancy; Retrospective Studies; Stillbirth
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/j.jpeds.2014.09.030

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). Study design 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.