Indirect Hyperbilirubinemia at birth – Is it all physiological? Presenter: Smita Malhotra - Apollo Hospital, New Delhi Moderator: Anupam Sibal Pediatric Gastroenterologist , Apollo Hospital, New Delhi Panelists Ujjal Poddar Pediatric Gastroenterologist, SGPGI, Lucknow Girish Gupte Pediatric Hepatologist, Birmingham Children’s Hospital, UK Alka Jadhav Pediatric Gastroenterologist, LTMGH, Sion, Mumbai

Indirect hyperbilirubinemia at birth Is it all physiological? Dr. Smita Malhotra Apollo Centre for Advanced Pediatrics Indraprastha Apollo Hospitals, Delhi

Product of consanguineous marriage 27 months Female Qatar Product of consanguineous marriage

Jaundice since D2 of life

Total Bilirubin 25 mg% Indirect Bilirubin 23.2 mg%

High Indirect Bilirubin Direct coomb’s test Positive Increased Hb/HaematocritDelayed cord clamping Maternal foetal or twin – twin transfusion Direct coomb’s test Positive Coomb’s test negative Isoimmunization Rh incompatibility ABO incompatibility Minor group incompatibility Normal / Low – Hb/Hct. RBC – normal Reticulocyte count – normalExtravascular blood - Cephalhaematoma, Bruises Increased entero – hepatic circulation Pyloric stenosis Intestinal obstruction Swallowed blood Metabolic / Endocrine problems Criggler – Najjar syndrome Hypothyroidism Breast milk jaundice etc   RBC Morphology abnormal High reticulocyte countABO incompatibility G6PD deficiency α – thalassaemia Spherocytosis / Elliptocytosis Disseminated intravascular coagulation (D.I.C.)  

No hematoma No blood group incompatibility No evidence of sepsis No evidence of hemolysis CBC/PS/Retic’s/G6PD/DCT LFT normal TFT normal

Multiple exchange transfusions Mutation analysis in Europe at 4 months ? Criggler Najjar Syndrome type 1 Phototherapy Multiple exchange transfusions Mutation analysis in Europe at 4 months

Phototherapy for 18 hours/day Bilirubin 16-18 mg/dl Home phototherapy Phototherapy for 18 hours/day Bilirubin 16-18 mg/dl

LT advised at IAH at 1 year of age LDLT at 27 months

At admission Weight 14.8 kg Deeply icteric No organomegaly No ascites Unsteady gait LL power 4/5 Ankle jerk weak Plantars flexor

Indirect hyperbilirubinemia Total bilirubin 29.31 mg/dL, direct 0.53 AST 41 U/l ALT 46 U/l Alkaline phosphatase 218 Prothrombin time 12.4 sec

Pediatric neurologist BERA – Normal MRI brain Altered signal intensity in putamen Pediatric neurologist Cleared for LRLT Neurological improvement likely

Pre transplant evaluation Nutritional status Vaccination

Complete haemogram Cultures Coagulation studies KFT Thyroid function tests Urine P/Cr ratio

Viral markers CXR ECG ECHO Dental clearance ENT clearance

USG doppler Normal span of liver and spleen Normal flow pattern in PV/HA/HV CT angiography abdomen

Segment II and III graft from the left lobe Donor- Father Recovered well Discharged 21 days after liver transplantation

Post transplant 5 years post transplant doing well with normal liver function and a serum bilirubin of 0.8 mg/dL Neurological status- normal

Criggler Najjar syndrome Inborn error of liver metabolism Rare (I in 1,000,000) and severe AR disorder UGT1A1 mutation Hereditary nonhemolytic unconjugated jaundice

Type 1 Complete absence of UGT activity Bil 15-50 mg/dl Risk for kernicterus Type 2 Partial enzyme activity Inducible with phenobarbitone Lower bilirubin levels

High-performance liquid chromatography of bile Tissue enzyme assay of a liver biopsy sample Mutation studies

Treatment Phototherapy Exchange transfusions LT- only definitive Rx Future options Hepatocyte transplant Gene therapy