Neonatal hemochromatosis attributed to gestational alloimmune liver disease treated with intravenous immunoglobulin and exchange transfusion therapy: an evidence-based case report

Neonatal hemochromatosis (NH) is a rare fatal liver disease accompanied by hepatic and extrahepatic iron overload.1-3 Gestational alloimmune liver disease (GALD) is a materno-fetal alloimmune disorder and leading cause of NH.2,4,5 This condition allows an interplay between the maternal adaptive immune system and the fetus, resulting in an allograft to the mother. The mother becomes sensitized to an alloantigen expressed by the fetus and forms specific reactive antibodies. Immunoglobulin G (IgG) is transported through the placenta and attacks the fetal hepatocytes, resulting in severe loss of hepatocytes and fetal iron overload.3,6 Liver transplantation has been the only definitive treatment for NH for many years, with a survival rate of ±35%. Conventional therapy containing antioxidants and chelation agents reportedly have very poor success, with survival rate of only 10-20%. A new treatment paradigm involving intravenous immunoglobulin (IVIG) and exchange transfusion (ET) therapy has shown significant success in survival rate in NH, decreasing the need for liver transplantation.3,7,8 Here we present a case of NH caused by GALD and treated successfully with a combination of IVIG therapy and ET. We also aimed to evaluate the efficacy of IVIG and ET therapy for NH.

The clinical variations and diagnostic challenges of deoxyguanosine kinase deficiency: a descriptive case series

Objectives Deoxyguanosine kinase (DGUOK) deficiency is one of the leading causes of the mitochondrial DNA-depletion syndromes (MDDS) associated with hepatocerebral involvement. Herein, we present four cases of DGUOK deficiency to emphasize the clinical variability of disease and the challenges in the diagnosis of DGUOK deficiency. Case presentation Hepatomegaly, hyperlactatemia, elevated alpha fetoprotein (AFP), alanine, and transaminase levels were detected in all patients, and cholestasis, coagulopathy, and hypotonia were common findings. All patients had a low birth weight, one patient underwent liver transplantation (LT). Clinical and laboratory findings of two patients and one patient suggested neonatal hemochromatosis and type 1 tyrosinemia, respectively. All patients were diagnosed with DGUOK deficiency by performing molecular genetic analysis. Conclusions Mitochondrial DNA-depletion syndromes should be kept in mind in cases in which hypotonicity, lactic acidosis, and neonatal cholestasis are observed. DGUOK deficiency may present in different clinics suggesting neonatal hemochromatosis or tyrosinemia type 1.

The Effect of Prenatal and Postnatal Treatment with Intravenous Immunoglobulin on Severity of Neonatal Hemochromatosis: The Tale of Two Brothers (Case Report)

Background Neonatal hemochromatosis (NH) is a rare condition that was the main reason for liver transplantation in infants. With the realization that NH results from the fetal complement-mediated liver injury, intravenous immunoglobulins (IVIG) were successfully introduced for the treatment. Case Presentation We present two cases of NH from the same family to illustrate the role of antenatal treatment with IVIG in alleviation and possible prevention of this serious morbidity. Conclusion A prenatal treatment and early postnatal administration of IVIG are effective ways to manage NH that help to reduce the severity of the symptoms, prevent liver failure, and avoid the need for liver transplantation.

The Effect of Prolonged Antenatal IVIG Treatment on the Development of Gestational Alloimmune Liver Disease in the Neonate

Introduction: Gestational Alloimmune Liver Disease (GALD) is a rare disease characterized by subacute fetal liver injury and often accompanied by hepatic and extrahepatic iron deposition. Findings include hypoglycemia, coagulopathy, hypoalbuminemia, elevated serum ferritin, elevated alpha-fetoprotein, and ascites. Extrahepatic hemosiderin deposition is often seen in salivary glands. Previously, the mortality rate was close to 80% with all patients needing liver transplantation. With maternal IVIG treatment and changes in neonatal treatment, there is now less than 20% mortality with infrequent need for liver transplantation. Diagnosis of GALD is typically done on a postmortem analysis. Case Description: A term female infant was born via scheduled c-section to a 32 year old G2P1000 mother who had been receiving weekly IVIG during this pregnancy due to the death of her first child at 4 days of life. Autopsy of that female baby demonstrated extensive neuropathological changes, liver steatosis, iron depletion, and ascites, consistent with GALD. Following delivery of our current patient, there was an elevated alpha-fetoprotein (greater than 80,000), decreased fibrinogen, and coagulopathy with peak international normalized ratio of 1.6. The patient received fresh frozen plasma and IVIG on day of life 1 with improvement of these levels. Complete blood count, liver function tests, and ammonia were within normal limits. An MRI of the liver demonstrated normal size, morphology, and normal iron levels based on T2 relaxometry. A buccal biopsy did not demonstrate extrahepatic iron deposition. MRI of the brain showed significant stenosis of the right transverse and sigmoid sinus relating to dural venous sinus thrombosis. There was no evidence of parenchymal infarction and no evidence of iron deposition. At this time, enoxaparin was initiated. The patient was discharged home on day of life nine on enoxaparin therapy. Discussion: There are few reported cases of patients with GALD, especially after maternal IVIG treatment. This case report exemplifies the effect of antenatal IVIG infusions during subsequent pregnancies in women with a history of GALD in prior children. This effect is protective, evidenced by lack of liver injury noted in this patient. This supports the use of immunotherapy during pregnancy to prevent recurrence of alloimmune injury. References: 1. Is exchange transfusion a possible treatment for neonatal hemochromatosis? Giuseppina Timpani-Francesca Foti-Antonino Nicolò-Pier Nicotina-Emanuele Nicastro-Raffaele Iorio - Journal of Hepatology - 2007 2. Medical and surgical treatment of neonatal hemochromatosis: Single center experience-Thomas Heffron-Todd Pillen-David Welch-Massimo Asolati-Gregory Smallwood-Phil Hagedorn-Carlos Fasola-David Solis-John Rodrigues-Jill Depaolo-James Spivey-Enrique Martinez-Stuart Henry-Rene Romero - Pediatric Transplantation - 2007 3. Neonatal Hemochromatosis: A Congenital Alloimmune Hepatitis - Peter Whitington - Seminars in Liver Disease - 2007 4. Neonatal hemochromatosis: The importance of early recognition of liver failure Pankaj Vohra-Cindy Haller-Sukru Emre-Margret Magid-Ian Holzman-Ming Ye-Elizaveta Iofel-Benjamin Shneider - The Journal of Pediatrics - 2000 5. Neonatal Liver Cirrhosis Without Iron Overload Caused by Gestational Alloimmune Liver Disease. Debray-François Guillaume de Halleux- Virginie Guidi-Ornella Detrembleur-Nancy Gaillez-Stéphanie Rausin-Léon Goyens-Philippe Pan-Xiaomin Whitington Peter-Pediatrics-2012 6. Neonatal Liver Failure and Congenital Cirrhosis due to Gestational Alloimmune Liver Disease: A Case Report and Literature Review Oscar Roos Mariano da Rocha Carolina-Renata Rostirola Guedes- Carlos Oscar Kieling- Marina Rossato Adami- Carlos Thadeu Schmidt Cerski- Sandra Maria Conçalvez Vieria - Hindawi - 2017 Image: (A) MRI liver showing normal appearance without evidence of hemochromatosis (B) MRI brain showing no evidence of iron deposition within the brain parenchyma (C) MRV head showing right transverse and sigmoid venous sinus thrombosis Figure Disclosures No relevant conflicts of interest to declare.

Intravenous Immune Globulin Uses in the Fetus and Neonate: A Review

Intravenous immune globulin (IVIG) is made after processing plasma from healthy donors. It is composed mainly of pooled immunoglobulin and has clinical evidence-based applications in adult and pediatric populations. Recently, several clinical applications have been proposed for managing conditions in the neonatal population, such as hemolytic disease of the newborn, treatment, and prophylaxis for sepsis in high-risk neonates, enterovirus parvovirus and COVID-19 related neonatal infections, fetal and neonatal immune-induced thrombocytopenia, neonatal hemochromatosis, neonatal Kawasaki disease, and some types of immunodeficiency. The dosing, mechanism of action, effectiveness, side effects, and adverse reactions of IVIG have been relatively well studied in adults but are not well described in the neonatal population. This review aims to provide the most recent evidence and consensus guidelines about the use of IVIG in the fetus and neonate.

NEONATAL HEMOCHROMATOSIS: A RARE CASE REPORT WITH CONSANGUINITY

Background: Neonatal hemochromatosis (NH) is a rare and severe liver disease of mainly intra-uterine onset, characterized by neonatal liver failure, hepatic and extrahepatic iron acquisition.NH is also called as Gestational alloimmune liver disease (GALD). This leads to an altered iron metabolism with resulting siderosis ,multi-organ failure and infants may be stillborn or present with advance, overwhelming liver disease. The disease represents the most common cause of liver failure in neonates and is also the most common indication for neonatal liver transplantation. We present an neonate who died at 15 days of age,and who was found to have massive iron overload in the liver. Initial treatment consisted of chelation therapy and antioxidants, but lack of laboratory and clinical improvement led to an exchange transfusion followed by intravenous immunoglobulin (IVIG). Irrespective of all above treatment no improvement of general condition of the patient. The unfavourable course of the disease is described in this case report.