Neonatal hemochromatosis - A fulminant cause of neonatal cholestasis

Abstract

Neonatal hemochromatosis (NH) due to Gestational alloimmune liver disease (GALD) is a rare form of fulminant liver disease of unknown cause characterized by diffuse deposition of iron in the liver and extra hepatic sites without any evidence of increased iron intake. Neonatal cholestasis is characterized by persistent elevation of conjugated bilirubin. It can be caused by infections, biliary atresia, by toxins or by metabolic disorders of the liver. GALD is rarely reported as a cause of fulminant neonatal cholestasis. We present three cases of infants who presented with neonatal cholestasis and were found to have NH as well. Case Report Neonatal hemochromatosis (NH) is a rare and severe disorder characterized by excessive iron deposition in liver and extra hepatic sites. It is characterized by neonatal liver failure with an in utero onset.1 Gestational alloimmune liver disease (GALD) is a leading cause of NH. The pregnancy may be complicated either by oligohyraminous or growth retardation and sometimes may cause stillbirth.2 Neonatal cholestasis is defined as the prolonged elevation of serum levels of conjugated bilirubin beyond the first 14 days of life. The overall incidence of neonatal cholestasis is estimated to be 1 in every 2500 live births.3 The most common causes of neonatal cholestasis include biliary tract anomalies of which biliary atresia is the commonest, metabolic disorders of the liver, infections or it may be idiopathic.4 A study has shown metabolic disorders of the liver to contribute to 8.6% of the total cases of neonatal cholestasis.5 Amongst the metabolic disorders causing neonatal cholestasis, alpha-1antitrypsin deficiency is the commonest; others include tyrosinemia, galactosemia, and hypothyroidism, inborn errors of bile acid metabolism, Alagille syndrome. Though NH can cause neonatal cholestasis, however it is not listed as a common metabolic cause of neonatal cholestasis.6 We report three cases of infants who fit the diagnostic criteria for NH and were found to have fulminant neonatal cholestasis without evidence of any other etiology of cholestasis. Case 1: A 1 month old boy born of non consanguineous marriage presented with jaundice and high coloured urine since birth, progressive abdominal distension for 15 days and blood in stools since yesterday. There is no clay coloured stools. Mother had no fever or rash during pregnancy. On examination, there is jaundice with anasarca and splenomegaly. Child was altered with left sided hemiparesis. Investigations are depicted in Table 1. Ultrasound abdomen (USG) showed splenomegaly. Urine aminoacidogram showed increased cysteine. Serum alpha fetoprotein was normal. TORCH titres were negative. Triglycerides were normal and Fibrinogen was< 45 ng/ml. He was treated with fresh frozen plasma, lactulose, metronidazole and intravenous fluids. Child subsequently died next day before any further tests could be done. Case 2: A 2 day old newborn was referred to for evaluation of conjugated hyperbilirubinemia. He was born of a full term normal delivery of a nonconsanguineous marriage. He weighed 3.5 kg and had cried immediately after birth. On examination, he was deeply jaundiced with hepatosplenomegaly. Investigations are depicted in Table 1. Serum bilirubin kept fluctuating between 31.5 to 54.40 mg/ dl throughout the admission. TORCH serology was negative. Blood and urine culture were negative. Serum triglycerides (150 mg/dl) and fibrinogen (262 mg/dl) were normal. Total serum iron was high (238 mg/dl, Normal 76-198 g/dl) with total iron binding capacity (TIBC) of 289g/dl (Normal 262-474 g/dl) and reduced transferrin saturation (24.7%, Normal 25-35%). MRI of abdomen showed iron deposits in liver and spleen but not in the pancreas. He was started on N -acetylcysteine, Vitamin E, prostaglandin E, deferoxamine, fresh frozen plasma but he continued to remain jaundiced and stared developing edema and ascitis on day 4 of admission along with increasing serum ferritin. He developed respiratory distress and had to be ventilated following which he died due to a pulmonary bleed on Day 5 of hospitalization. Intravenous immunoglobulin (IVIG) could not be given due to non-affordability. Postmortem, parents refused a liver biopsy or a buccal biopsy. Case 3: A 2 1⁄2 months old boy, first by birth order, born of non-consangineous marriage presented Address for Correspondance: Dr Drishti Tolani, Division of Pediatric Cardiology, The Children’s Hospital of Michigan, Detroit, MI, USA. Email: drishtolani@hotmail.com ©2021 Pediatric Oncall ARTICLE HISTORY Received 15 August 2021 Accepted 7 September 2021