Neonatal Hemochromatosis: Diagnostic Work-Up Based on a Series of 56 Cases of Fetal Death and Neonatal Liver Failure - 25/10/14

Doi : 10.1016/j.jpeds.2014.09.030

Sophie Heissat, MD ^1,^⁎ , Sophie Collardeau-Frachon, MD, PhD ², Julien Baruteau, MD ³, Estelle Dubruc, MD ², Raymonde Bouvier, MD ², Monique Fabre, MD ⁴, Marie Pierre Cordier, MD ⁵, Pierre Broué, MD ³, Vincent Guigonis, MD, PhD ⁶, Dominique Debray, MD, PhD ⁷
¹ Department of Pediatric Gastroenterology and Hepatology, Hôpital Femme Mère Enfant, Hospices Civils de Lyon et Université Lyon 1
² Department of Pathology, Hôpital Femme Mère Enfant, Hospices Civils de Lyon et Université Lyon 1, Lyon, France
³ Department of Pediatric Hepatology and Metabolic Diseases, Toulouse, Toulouse, France
⁴ Department of Pathology, Villejuif, France
⁵ Department of Genetics, Hôpital Femme-Mère-Enfant, HCL Lyon, Lyon, France
⁶ Department of Pediatrics, Hôpital Mère et Enfant, CHU Limoges, Limoges, France
⁷ Medical-Surgical Center, Hepatology, and Transplantation AP-HP, Hôpital Necker Enfants Malades, Paris, France

^∗Reprint requests: Sophie Heissat, MD, Gastroentérologie Hépatologie et Nutrition Pédiatrique, Hôpital Femme Mère Enfant, Hospices Civils de Lyon et Université Lyon 1, 59 Boulevard Pinel, 69500 Bron, France.

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Saturday 25 October 2014

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).

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.

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Keyword : DGUOK, EHS, ET, GA, GALD, HLH, HUS, IDACH, IUGR, IV-IG, MRCD, MRI, NH, NH-GALD, NLF, RES