Eresha Jasinge

Novel mutations in the glucocerebrosidase gene of Indian patients with Gaucher disease

Correction to: Journal of Human Genetics (2014) 59, 223–228. doi:10.1038/jhg.2014.5; published online 13 February 2014. The authors of the above paper noticed errors in Table 2 on publication that are shown below: 1. Change patient #22’s genotype from L444P (c.1448T>C)/L444P (c.1448T>C) to L444P (c.

First contiguous gene deletion causing biotinidase deficiency: The enzyme deficiency in three Sri Lankan children

We report three symptomatic children with profound biotinidase deficiency from Sri Lanka. All three children presented with typical clinical features of the disorder. The first is homozygous for a missense mutation in the BTD gene (c.98_104 del7insTCC; p.Cys33PhefsX36) that is commonly seen in the western countries, the second is homozygous for a novel missense mutation (p.Ala439Asp), and the third is the first reported instance of a contiguous gene deletion causing the enzyme deficiency. In addition, this latter finding exemplifies the importance of considering a deletion within the BTD gene for reconciling enzymatic activity with genotype, which can occur in asymptomatic children who are identified by newborn screening.

Lipoprotein Lipase Deficiency in an Infant With Chylomicronemia, Hepatomegaly, and Lipemia Retinalis

Lipoprotein lipase (LPL; EC 3.1.1.1.34) is a key enzyme needed for the hydrolysis of triacylglycerol in chylomicrons and very low density lipoproteins.1 LPL deficiency is a rare autosomal recessive disorder with a prevalence of ~1 in 1 000 000 in the United States and higher in other regions of the world.2 LPL deficiency is characterized biochemically by severe hypertriglyceridemia and clinically by features including failure to thrive, eruptive xanthomas, hepatosplenomegaly, recurrent pancreatitis, and lipemia retinalis.2Over 100 mutations in the LPL gene have been found in LPL deficiency. Dietary fat restriction is the mainstay of treatment.3 We report an infant with one novel and one reported mutation within exon 6 of the LPL gene who presented with chylomicronemia, hepatomegaly, and lipemia retinalis.

Dubin–Johnson syndrome and intrahepatic cholestasis of pregnancy in a Sri Lankan family: a case report

BackgroundDubin–Johnson syndrome and intrahepatic cholestasis of pregnancy are rare chronic liver disorders. Dubin–Johnson syndrome may manifest as conjugated hyperbilirubinemia, darkly pigmented liver, presence of abnormal pigment in the parenchyma of hepatocytes and abnormal distribution of the coproporphyrin isomers I and III in the urine. Intrahepatic cholestatic jaundice of pregnancy presents as pruritus, abnormal liver biochemistry and increased serum bile acids.Case presentationA Sri Lankan girl presented with recurrent episodes of jaundice. She had conjugated hyperbilirubinaemia with diffuse, coarse brown pigments in the hepatocytes. Urine coproporphyrin examination suggested Dubin–Johnson syndrome. Genetic studies confirmed missense homozygous variant p.Trp709Arg in the ATP-binding cassette sub-family C member 2 gene ABCC2 that encodes the Multidrug resistance-associated protein 2 that causes Dubin–Johnson syndrome. The gene study of the mother revealed the same missense variant in ABCC2/MRP2 but with a heterozygous status, and in addition a homozygous missense variant p.Val444Ala in the ATP-binding cassette, sub-family B member 11 gene ABCB11 that encodes the bile salt export pump.ConclusionDubin–Johnson syndrome should be considered when the common causes for conjugated hyperbilirubinaemia have been excluded, and patient has an increased percentage of direct bilirubin relative to total bilirubin concentration. Its early diagnosis prevents repeated hospital admissions and investigations. Knowledge of a well known homozygous variant in ABCB11 gene could help in the management of pregnancy.

Many pitfalls in diagnosis of acute intermittent porphyria: a case report

BackgroundAcute intermittent porphyria is a rare autosomal dominant disorder caused by a deficiency of the enzyme, hydroxymethylbilane synthase. Recognition of acute neurovisceral attacks can be difficult due to the nonspecific nature of symptoms.Case presentationWe report a case of 33-year-old male patient who presented with recurrent episodes of severe abdominal pain, nausea, vomiting, constipation and numbness of bilateral lower limb extremities. These nonspecific neurovisceral attacks were subject to medical and surgical misdiagnoses of acute appendicitis, sinus tachycardia, renal calculi, drug-induced acute interstitial nephritis and two episodes of partial intestinal obstruction. The sixth acute attack raised the suspicion of an acute porphyria. Watson and Schwartz test was positive for porphobilinogen in urine. Mutation analysis by DNA sequencing of the extracted DNA of the proband revealed a previously reported missense mutation, c.517C>T encoding p.R173W in the HMBS gene, confirming the diagnosis of Acute Intermittent Porphyria. Four out of five family members who underwent targeted mutation analyses were mutation-positive.ConclusionThe most common clinical presentation of Acute Intermittent Porphyria is abdominal pain with neurovisceral manifestations which are common to several medical, psychiatric and surgical pathologies. This leads to underdiagnosis and misdiagnosis of this disorder, incorrect management, and severe complications. Therefore, a high index of suspicion and awareness of front line laboratory investigations are important for diagnosis. Definitive diagnosis enables implementation of strategies to prevent acute attacks, and also triggers genetic testing and genetic counseling of at-risk family members.

Corrigendum to “First contiguous gene deletion causing biotinidase deficiency: The enzyme deficiency in three Sri Lankan children” [Mol. Genet. Metab. Rep. 2 (2016) 81–84]

[This corrects the article DOI: 10.1016/j.ymgmr.2015.01.005.].

Correction to: Dubin–Johnson syndrome and intrahepatic cholestasis of pregnancy in a Sri Lankan family: a case report

Following publication of the original article [1], the authors requested the following corrections:1.Author 2—given name should be Dilanthi and family name Warawitage.2.Author 6—given name should be Nalika and family name de Silva.

Uric acid, an important screening tool to detect inborn errors of metabolism: a case series

BackgroundUric acid is the metabolic end product of purine metabolism in humans. Altered serum and urine uric acid level (both above and below the reference ranges) is an indispensable marker in detecting rare inborn errors of metabolism. We describe different case scenarios of 4 Sri Lankan patients related to abnormal uric acid levels in blood and urine.Case 1A one-and-half-year-old boy was investigated for haematuria and a calculus in the bladder. Xanthine crystals were seen in microscopic examination of urine sediment. Low uric acid concentrations in serum and low urinary fractional excretion of uric acid associated with high urinary excretion of xanthine and hypoxanthine were compatible with xanthine oxidase deficiency.Case 2An 8-month-old boy presented with intractable seizures, feeding difficulties, screaming episodes, microcephaly, facial dysmorphism and severe neuro developmental delay. Low uric acid level in serum, low fractional excretion of uric acid and radiological findings were consistent with possible molybdenum cofactor deficiency. Diagnosis was confirmed by elevated levels of xanthine, hypoxanthine and sulfocysteine levels in urine.Case 3A 3-year-10-month-old boy presented with global developmental delay, failure to thrive, dystonia and self-destructive behaviour. High uric acid levels in serum, increased fractional excretion of uric acid and absent hypoxanthine–guanine phosphoribosyltransferase enzyme level confirmed the diagnosis of Lesch–Nyhan syndrome.Case 4A 9-year-old boy was investigated for lower abdominal pain, gross haematuria and right renal calculus. Low uric acid level in serum and increased fractional excretion of uric acid pointed towards hereditary renal hypouricaemia which was confirmed by genetic studies.ConclusionAbnormal uric acid level in blood and urine is a valuable tool in screening for clinical conditions related to derangement of the nucleic acid metabolic pathway.