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Year : 2017  |  Volume : 6  |  Issue : 1  |  Page : 34-36

A rare case of neonatal cholestasis

1 Department of Pediatric Medicine, Calcutta National Medical College, Kolkata, West Bengal, India
2 Department of Pathology, Calcutta National Medical College, Kolkata, West Bengal, India

Date of Web Publication8-Feb-2017

Correspondence Address:
Dr. Bhaswati Ghoshal
Souhardya Apartment, Bankimpally, Madhyamgram, Kolkata - 700 129, West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2249-4847.199759

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A term appropriate for gestational age neonate presented with severe cholestasis with features of acute hepatic failure in early neonatal life. There was hypoglycemia, hyperammonemia, cholestasis, ascites, and hepatomegaly. Buccal mucosal biopsy containing minor salivary gland revealed iron deposition on Prussian blue staining suggestive of neonatal hemochromatosis. The neonate responded to exchange transfusion and intravenous immunoglobulin.

Keywords: Cholestasis, gestational alloimmune liver disease, neonatal hemochromatosis

How to cite this article:
Ghoshal B, Das A, Mondal T. A rare case of neonatal cholestasis. J Clin Neonatol 2017;6:34-6

How to cite this URL:
Ghoshal B, Das A, Mondal T. A rare case of neonatal cholestasis. J Clin Neonatol [serial online] 2017 [cited 2020 Jul 12];6:34-6. Available from: http://www.jcnonweb.com/text.asp?2017/6/1/34/199759

  Introduction Top

Cholestatic jaundice affects approximately 1 in every 2500 infants and has a multitude of causes.[1] The number of unique disorders presenting with cholestasis in the neonatal period may be greater than at any other time in life and includes infections, anatomic abnormalities of the biliary system, endocrinopathies, genetic disorders, metabolic abnormalities, toxin and drug exposures, vascular abnormalities, neoplastic processes, and other miscellaneous causes.[2] Of the many conditions that cause neonatal cholestasis, the most commonly identifiable are biliary atresia (25%–35%), genetic disorders (25%), metabolic diseases (20%), and a1-antitrypsin (A1AT) deficiency (10%).[3] Rarely, severe liver failure of prenatal origin can present as severe cholestasis in the 1st week of life.

  Case Report Top

A term appropriate for gestational age, boy baby, birth weight of 2.82 kg, was born to a 24-year-old G2P1 mother by normal delivery at a peripheral primary health center. The child cried at birth and received breastfeeding since birth. The child was referred to Medical College Hospital for suspected sepsis with jaundice on the 3rd day of postnatal age. On admission, total bilirubin was 21 mg/dl with conjugated bilirubin of 2.7 mg/dl. There was no significant antenatal history, no history of consanguinity, mother was Rh positive, no history of blood group incompatibility, and the previous sibling was normal. At the time of admission, capillary blood glucose was 17 mg%. The whole blood sampling for random sugar also was of similar value. The child received intravenous dextrose infusion at admission with glucose infusion rate of 12 mg/kg/min to stabilize blood sugar. The child received intensive phototherapy. There was gradual abdominal distension due to enlargement of liver size since admission. At the time of admission, liver was palpable 2 cm below mid-clavicular line (MCL), which enlarged to 7 cm (below MCL) on day 6 of postnatal age. Splenomegaly was also present. On the 6th day of admission, there was gastrointestinal bleeding with gradual increase in jaundice. Prothrombin time was 19 s, activated partial thromboplastin time was 220 s, and International Normalized Ratio was 1.6. The platelet count was 37,000. The child developed ascites and progressive increase in icterus. On 8th day of life, total bilirubin was 38 mg%, with conjugated bilirubin of 20 mg%. Stool color was pale. Sensorium was depressed initially for 10 days. The child was not tolerating oral feeds and required intravenous alimentation till day 29 of life. The child's blood group was A positive and mother's was B positive. TORCH screening was negative. Thyroid-stimulating hormone was 2 µIU/ml. The reticulocyte count was 2%. Glucose-6-phosphate dehydrogenase deficiency was not detected. Aspartate transaminase was 308 units on day 6 of life and alanine transaminase was 280 units on day 6 of life. Total protein was 7 g/dl and albumin was 3 g/dl. Glucose infusion rate of 12 mg/kg/min was required till day 30 of postnatal age. Tandem mass spectrometry screening for inborn error of metabolism was negative. Urine for reducing substance, ketone body, and organic acid was negative. Serum cortisol, insulin, and lactate were normal. Serum ammonia level increased (1140 µg/dl). Ultrasonography of hepatobiliary system ruled out any surgical cause of jaundice. Gamma-glutamyl transpeptidase was 17.7 µ/L (range: 11–50 µ/L), serum ferritin was 909.82 ng/dl (range: 90–160 ng/dl), alpha fetoprotein was 550518.92 ng/ml (88000-412000ng/ml), serum triglyceride was 180 mg/dl, and A1AT level was normal (2.99 ng/L). Liver biopsy could not be done due to lack of parental consent. Blood culture was negative. As there was early-onset liver failure, neonatal hemochromatosis (NH) was suspected. Buccal smear was tested for iron deposition by Prussian blue stain, which was positive [Figure 1]. Treatment given was phototherapy on admission followed by exchange transfusion, intravenous immunoglobulin 500 mg/kg two doses, blood transfusion, and supplementation of multivitamins. The child improved completely and was discharged on the 35th day of postnatal age [Table 1].
Figure 1: Prussian blue stain of oral mucosa and minor salivary gland showing iron deposition

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Table 1: Investigation report

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  Discussion Top

NH is a rare cause of neonatal cholestasis presenting as liver failure in early neonatal life. It is characterized by neonatal liver failure or fetal death secondary to severe hepatic injury with hepatic and extrahepatic siderosis sparing the reticuloendothelial system. NH carries a recurrence rate of 90% in the progeny of affected women.[4] NH refers to the clinical diagnosis of hepatic failure that is largely caused by gestational alloimmune liver disease (GALD). Other causes of the NH phenotype include perinatal infection, trisomy 21, metabolic disorders and inborn errors of metabolism, and various syndromes (growth retardation, aminoaciduria, cholestasis, iron overload, lactic acidosis, and early death, trichohepatoenteric, and Martinez–Frias syndrome), but these causes account for a total of 2% of NH cases.[5] Inheritance pattern was not consistent with the genetic explanation because women may have a history of multiple unaffected pregnancies before having a child who is affected, followed by a 90% probability of subsequently affected infants after the index case. The hepatic iron deposition characteristically seen in NH is likely the result of liver injury rather than the cause of it. The control of iron efflux from the mother to the fetus is normally controlled through the interaction of hepcidin (a 25 amino acid protein exclusively produced by fetal liver) with ferroportin (a transmembrane transporter highly expressed in placental cells). NH-GALD liver injury results in significant hepcidin production deficiency. This leads to impaired feedback control of placental iron flux, and therefore the ferroportin-mediated transfer of iron to the fetal liver is increased. In addition, transferrin production is decreased, possibly secondary to decreased hepatic transferrin gene expression, leading to reduced iron-binding capacity and increased circulating unbound iron. Although elevated serum ferritin was previously considered a biological marker of NH, it was recently demonstrated to be a nonspecific marker of hepatocellular injury potentially resulting from massive hepatic necrosis, systemic inflammation, or decreased hepatic clearance.[6] The definitive diagnosis of NH can only be confirmed by the demonstration of iron accumulation in extrahepatic tissue, usually through a deep buccal salivary gland biopsy. Other organs that can be affected include the Brunner's glands, parathyroid glands, thymus, renal tubules, pancreatic islets, adenohypophysis, hyaline cartilage chondrocytes, and gastric gland. The spleen, lymph nodes, and bone marrow typically do not demonstrate iron deposition in NH, as the reticuloendothelial system is characteristically spared.[5] T2-weighted magnetic resonance imaging also can detect iron deposition in hepatic and extrahepatic sites.[5] Chu et al. reported a series of two similar cases of NH presenting with acute hepatic necrosis, cholestasis, and bleeding disorder in early neonatal life improving on similar treatment.[7] Koura et al. reported a case of hemochromatosis with renal tubular dysgenesis requiring peritoneal dialysis.[8] Renal function was normal in the present case.

  Conclusion Top

NH should be suspected in any neonate, evidencing severe liver dysfunction shortly after birth.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Balistreri WF. Neonatal cholestasis. J Pediatr 1985;106:171-84.  Back to cited text no. 1
Suchy FJ. Neonatal cholestasis. Pediatr Rev 2004;25:388-96.  Back to cited text no. 2
Balistreri WF, Bezerra JA. Whatever happened to “neonatal hepatitis”? Clin Liver Dis 2006;10:27-53, v.  Back to cited text no. 3
Whitington PF, Kelly S. Outcome of pregnancies at risk for neonatal hemochromatosis is improved by treatment with high-dose intravenous immunoglobulin. Pediatrics 2008;121:e1615-21.  Back to cited text no. 4
Feldman AG, Whitington PF. Neonatal hemochromatosis. J Clin Exp Hepatol 2013;3:313-20.  Back to cited text no. 5
Lee WS, McKiernan PJ, Kelly DA. Serum ferritin level in neonatal fulminant liver failure. Arch Dis Child Fetal Neonatal Ed 2001;85:F226.  Back to cited text no. 6
Chu A, Burrito TD, Kesavan K, Hageman JR, Azzam R. Neonatal hemochromatosis: Evaluation of then neonate with hepatic failure. Neoreviews 2016;17:e154-9.  Back to cited text no. 7
Koura U, Horikawa S, Okabe M, Kawasaki Y, Makimoto M, Mizuta K, et al. Successful treatment of hemochromatosis with renal tubular dysgenesis in a preterm infant. Clin Case Rep 2015;3:690-3.  Back to cited text no. 8


  [Figure 1]

  [Table 1]

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