Objectives: To determine the common clinical presentations, common aetiological factors, average age at presentation and possible means of early detection of cholestasis by primary health care workers. Method: This prospective, descriptive study analyzed 60 infants less than six months old who presented to Lady Ridgeway Hospital from October 2013 to January 2015 with evidence of cholestasis. Results: The common clinical features were jaundice (100%), hepatomegaly (83.3%), pale stools (76.6%), dark urine (61.6%) and splenomegaly (56.6%). The common causes were idiopathic neonatal hepatitis (INHS) (26.6%) and biliary atresia (26.6%). Nine cases of INHS were transient. Sepsis (15%), multifactorial (13.3%) and cytomegalovirus infection (6.6%) were the other frequent causes. The less frequent causes were Alagille syndrome (3.2%), birth asphyxia (1.6 %), progressive familial intrahepatic cholestasis (PFIC) (1.6%), biliary sludge due to haemolysis (1.6%), intestinal obstruction (1.6%) and multiple small gall bladder calculi (1.6%). The average age at presentation of infants with cholestasis was 64.2 days and the mean age at presentation of infants with cholestasis who were eventually diagnosed as biliary atresia was 81.8 days.

Background Iron overload (IO) is a complication in transfusion dependent beta thalassaemia (TDT). Pathogenic variants in genes involving iron metabolism may confer increased risk of IO. The objective of this study was to determine the magnitude of the cardiac and hepatic IO and determine whether pathogenic variants in HFE, SLC40A1 and TFR2 genes increase the risk of IO in a cohort of TDT patients in Sri Lanka. Materials and Methods Fifty-seven (57) patients with TDT were recruited for this study. Serum ferritin was done once in 3 months for a period of one year in all. Those who were ≥ 8 years of age (40 patients) underwent T2* MRI of the liver and heart. Fifty-two (52) patients underwent next generation sequencing (NGS) to identify pathogenic variants in HBB, HFE, SLC40A1 and TFR2 genes. Results The median age of the patients of this cohort was 10 years. It comprised of 30 (52.6%) boys and 27 (47.4%) girls. The median level of serum ferritin was 2452 ng/dl. Hepatic IO was seen in 37 (92.5%) patients and cardiac IO was seen in 17 (42.5%) patients. There was no statistically significant correlation between serum ferritin and hepatic or cardiac IO. Thirty-two (61.5%), 18 (34.6%), 2 (3.8%) of patients were homozygotes, compound heterozygotes and heterozygotes for pathogenic variants in the HBB gene. Eight (15.4%) and 1 (1.9%) patients were heterozygotes for pathogenic and likely pathogenic variants of HFE genes respectively. There were no pathogenic variants for the TfR2 and SLC40A1 genes. The heterozygotes of the pathogenic variants of the HFE were not at increased risk of IO. Conclusions Cardiac T2* MRI helps to detect cardiac IO in asymptomatic patients. It is important to perform hepatic and cardiac T2* MRI to detect IO in patients with TDT. There was no statistically significant correlation between pathogenic variants of HBB and HFE genes with hepatic and cardiac IO in this cohort of patients.

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Background. Iron overload (IO) is a complication in transfusion dependent beta thalassaemmia (TDT). Pathogenic variants in genes involving iron metabolism may confer increased risk of IO. The objective of this study was to determine the magnitude of the cardiac and hepatic IO and determine whether pathogenic variants in HFE, SLC40A1 and TFR2 genes increase the risk of IO in a cohort of TDT patients in Sri Lanka.Materials and Methods. Fifty-seven (57) patients with TDT were recruited for this study. Serum ferritin was done once in 3 months for one year in all. Those who were ≥ 8 years of age underwent T2* MRI of the liver and heart. Fifty-two (52) patients underwent next generation sequencing (NGS) to identify pathogenic variants in HBB, HFE, SLC40A1 and TFR2 genes.Results. The mean age (SD) of this cohort was 9.5 (±4.6) years. It comprised of 30 (52.6%) boys and 27 (47.4%) girls. The mean serum ferritin was 3405 (±2670.5) ng/dl. Hepatic IO was seen in 38 (95%) patients and cardiac IO was seen in 17 (42.5%) patients. All patients with cardiac IO were asymptomatic and had normal echocardiogrammes. There was no statistically significant correlation between serum ferritin and hepatic or cardiac IO.32 (61.5%), 18 (34.6%), 2 (3.8%) of patients were homozygotes, compound heterozygotes and heterozygotes for pathogenic variants in the HBB gene. 9 (17.3%) and 3 (5.8%) patients were heterozygotes for pathogenic variants of HFE and SLC40A1 genes respectively. There were no pathogenic variants for the TfR2 gene. The heterozygotes of the pathogenic variants of the HFE and SLC40A1 genes were not at increased risk of IO.Conclusions. Cardiac T2* MRI helps to detect cardiac IO prior to the onset of symptoms when the echocardiogramme is normal. It is important to perform hepatic and cardiac MRI T2* to detect IO in patients with TDT.

Abetalipoproteinemia (ABL) is a rare autosomal recessive disorder of lipoprotein metabolism caused by mutations in the microsomal triglyceride transfer protein (MTTP) gene. To date, less than 100 cases of ABL have been reported worldwide. It is characterized biochemically by the absence or extremely low levels of low-density lipoproteins in the blood. We report a four-month-old girl, born to consanguineous parents, who presented with steatorrhea, failure to thrive, marked hypolipidemia and acanthocytosis, with a similar history having been noted in her older sibling. DNA sequencing revealed the infant to be homozygous for a novel pathogenic MTTP splice variant c.394-2A˃C. Family screening revealed her sister to be homozygous for the same MTTP variant while her parents were heterozygotes. Early diagnosis and treatment of ABL in the form of a low-fat diet and fat-soluble vitamin supplementation can mitigate neuropathy and retinopathy. We believe that this is the first identification of an infant with a novel mutation for abetalipoproteinemia in Sri Lanka.