Genotypic Spectrum in a Cohort of Sri Lankan Patients With Homocystinuria.

Homocystinuria due to cystathionine beta-synthase (CBS) deficiency is a rare metabolic disorder inherited as an autosomal recessive trait. Spectrum of genetic variants in gene and their correlation with the phenotypes of homocystinuria in Sri Lankan patients have not been reported to date. The objective of this study was to identify the genotypes and genotype-phenotype correlations in a cohort of Sri Lankan patients with homocystinuria due to CBS deficiency.

Dihydropyrimidinase enzyme deficiency and congenital isolated adrenocorticotrophin deficiency: dual genetic diagnosis in a Sri Lankan boy.

We report on a male patient who was investigated for frequent apneic episodes, feeding problems, hypotonia, and left-sided middle cerebral artery infarction in the magnetic resonance imaging at 2 weeks of age. Primary diagnosis of dihydropyrimidinase (DPYS) deficiency was suspected following the analysis of urine for organic acid; DPYS deficiency was strongly suggested by the presence of dihydrouracil, thymine, and uracil. Subsequent genetic evaluation by whole exome sequencing revealed 2 separate mutations, homozygous pathogenic variant c.

Association of selected genetic variants in CBS and MTHFR genes in a cohort of children with homocystinuria in Sri Lanka.

Background: Homocystinuria is an inherited, inborn error of homocysteine metabolism, which leads to the abnormal accumulation of homocysteine and its metabolites in blood and urine, resulting in various complications. Variants in the cystathionine β-synthase (CBS) and methylenetetrahydrofolate reductase (MTHFR) genes interrupt the formation of the corresponding enzymes and prevent homocysteine from being metabolised; hence, the homocysteine levels in plasma increase than the optimum levels.

Materials And Methods: In the current study, eight clinically confirmed children with homocystinuria were detected to study the chosen variants in the CBS gene (c.

Clinical Presentation and Genetic Heterogeneity Including Two Novel Variants in Sri Lankan Patients With Infantile Sandhoff Disease.

Infantile Sandhoff Disease (SD) is a subtype of GM2 gangliosidosis, which is never been reported in Sri Lanka. Data of eight children, who were diagnosed with SD during the period of 2017 to 2021, were analyzed retrospectively. The aim of this study was to analyze genotypic and phenotypic variations of native SDs.

An integrated multiomic approach as an excellent tool for the diagnosis of metabolic diseases: our first 3720 patients.

To present our experience using a multiomic approach, which integrates genetic and biochemical testing as a first-line diagnostic tool for patients with inherited metabolic disorders (IMDs). A cohort of 3720 patients from 62 countries was tested using a panel including 206 genes with single nucleotide and copy number variant (SNV/CNV) detection, followed by semi-automatic variant filtering and reflex biochemical testing (25 assays). In 1389 patients (37%), a genetic diagnosis was achieved.

Non-specificity of symptoms in infantile-onset Pompe disease may delay the diagnosis and institution of treatment.

Pompe disease is an autosomal-recessive inherited disorder of glycogen metabolism due to lysosomal acid alpha-glucosidase deficiency. The infantile-onset form is rapidly fatal if left untreated and presents with respiratory symptoms, a typical encounter during infancy. We discuss two infants presenting with respiratory symptoms since early infancy and found to have cardiomegaly, hypotonia, elevated muscle enzymes, leading to the diagnosis of Pompe disease with genetic confirmation.

Incidental diagnosis of LPL deficiency in an infant presenting with an acute respiratory infection.

Lipoprotein lipase (LPL) deficiency is an extremely rare disorder of lipid metabolism known to cause hypertriglyceridaemia in childhood. We report the incidental diagnosis of LPL deficiency in an infant presenting with an acute respiratory tract infection. The patient was initially treated for a lower respiratory tract infection, but was subsequently found to have milky appearance of the serum, with a triglyceride concentration greater than 1000 mg/dL.

A Case of Carbamazepine-Induced Aggravation of Self-Limited Epilepsy with Centrotemporal Spikes Epilepsy and Valproate-Induced Hyperammonemic Encephalopathy in a Child with Heterozygous Gene Variant of Carbomoyl Phosphatase Synthetase Deficiency.

Antiepileptics drugs are the mainstay of the management of epilepsy in children. Sodium valproate (VPA) and carbamazepine (CBZ) are widely used medications in childhood epilepsy. Hyperammonemia has been described as a known side effect of valproate therapy.

A rare co-occurrence of duchenne muscular dystrophy, congenital adrenal hypoplasia and glycerol kinase deficiency due to Xp21 contiguous gene deletion syndrome: case report.

Background: Contiguous gene deletion syndromes are rare genomic disorders caused by deletion of large segments of DNA resulting in co-occurrence of apparently unrelated multiple clinical phenotypes. We report a boy with contiguous gene deletion involving Xp21 genomic location.

Case Presentation: A Sri Lankan boy with developmental delay and failure to thrive first presented at three years of age with hypovolaemia, hyperpigmentation and drowsiness.

Urine Organic Acid Analysis: Key Diagnostic Test for Fumaric Aciduria in a Sri Lankan Child.

Fumaric aciduria resulting from fumarate hydratase deficiency is a rare inherited disorder of the Krebs tricarboxylic acid cycle that is characterized by neurologic manifestations, a spectrum of brain abnormalities, and the excretion of fumaric acid in urine. We describe a 3 year old Sri Lankan boy who was referred at age 10 months with poor weight gain and hypotonia for further laboratory investigations. In addition to global developmental delay, there were noticeable dysmorphic features with a prominent forehead, low-set ears, micrognathia, and hypertelorism with persistent neutropenia.

A novel mutation in ACADVL causing very long-chain acyl-coenzyme-A dehydrogenase deficiency in a South Asian pediatric patient: a case report and review of the literature.

Background: Very long-chain acyl-coenzyme-A dehydrogenase deficiency is a rare, severe life-threatening metabolic disorder of mitochondrial fatty acid oxidation, caused by mutations in ACADVL gene. Here we present a genetically confirmed case of a South Asian baby girl with severe, early-onset form of very long-chain acyl-coenzyme-A dehydrogenase deficiency due to a novel mutation in ACADVL gene.

Case Presentation: Index case was the second baby girl of second-degree consanguineous South Asian parents.

Exome sequencing detected an extremely rare case of foetal onset familial haemophagocytic lymphohistiocytosis type 5 presenting with hydrops foetalis.

Background: Familial hemophagocytic lymphohistiocytosis (FHL) is a genetically heterogeneous autosomal recessive hyper-inflammatory syndrome which needs early accurate diagnosis and appropriate treatment to prevent complications and early mortality. Recently, it was reported that mutations in STXBP2 gene are linked to FHL type 5 (FHL-5).

Case Presentation: We report a Sri Lankan neonate who presented with low Apgar scores at birth, abdominal distension, and hepatosplenomegaly, followed by lethargy, poor sucking and rapid decompensation with wide spread activation of inflammation within 48 h of birth.

Cornea Verticillata in classical Fabry disease, first from Sri Lanka: a case report.

Background: Fabry disease is a rare inborn error of metabolism with profound clinical consequences if untreated. It is caused by the deficiency of α galactosidase A enzyme and is the only lysosomal storage disorder with an X linked inheritance. Confirmation requires genetic analysis of Galactosidase Alpha (GLA) Gene, which is often a challenge in resource-poor settings.

Lipin-1 Deficiency-Associated Recurrent Rhabdomyolysis and Exercise-Induced Myalgia Persisting into Adulthood: A Case Report and Review of Literature.

Phosphatidate phosphatase-1 (lipin-1) is encoded by gene. Lipin-1 deficiency has been reported as the second most common cause of early-onset rhabdomyolysis after primary fatty acid oxidation disorders. We report a case of a 32-year-old Sri Lankan female with a history of more than 10 episodes of rhabdomyolysis and exercise intolerance since childhood.

A Novel Mutation in Causing Beta-Ketothiolase Deficiency in a 4-Year-Old Sri Lankan Boy with Metabolic Ketoacidosis.

Beta-ketothiolase (mitochondrial acetoacetyl-CoA thiolase, T2) deficiency is a rare genetic disorder of ketone utilization and isoleucine catabolism caused by mutations in the gene. Here we report the first Sri Lankan case of T2 deficiency confirmed by genetic analysis. A 4-year-old boy presented with the first episode of severe metabolic ketoacidosis after a febrile illness.

GTP-Cyclohydrolase I deficiency presenting as malignant hyperphenylalaninemia, recurrent hyperthermia and progressive neurological dysfunction in a South Asian child - a case report.

Background: Tetrahydrobiopterin (BH) deficiencies are disorders affecting phenylalanine homeostasis, and catecholamine and serotonin biosynthesis. GTP-Cyclohydrolase I deficiency (OMIM 600225) is an extremely rare variant of inborn error of BH synthesis which exists in recessive and dominant forms. The recessive form presents with complex neurological and autonomic dysfunction whilst the dominant form presents as Dopa-responsive dystonia.

Phenotypic spectrum and genetic heterogeneity of cystic fibrosis in Sri Lanka.

Background: Cystic fibrosis has been largely under-diagnosed and thus, limited data is available on the incidence of cystic fibrosis in Sri Lanka. Our aim is to describe the phenotypic and genotypic spectrum of children with cystic fibrosis in Sri Lanka.

Case Presentation: This report describes 10 unrelated cystic fibrosis cases with phenotypic features of cystic fibrosis and abnormal or intermediate sweat tests.

Evaluation of biochemical and haematological changes in dengue fever and dengue hemorrhagic fever in Sri Lankan children: a prospective follow up study.

Background: Series of biochemical and haematological changes occur during the course of dengue infection, which vary depending on the clinical disease. The patterns of change are not well documented and identifying these patterns in children with dengue infection would help to anticipate the progression to different clinical stages thus enabling effective management.

Methods: A prospective follow up study was conducted during the period of July 2013 - April 2014 at Professorial Pediatric unit, Lady Ridgeway Hospital for Children, Colombo, Sri Lanka.

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

Background: Acute 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 Presentation: We 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.

A heterozygous variant in the SLC22A12 gene in a Sri Lanka family associated with mild renal hypouricemia.

Background: Renal hypouricemia is a rare heterogeneous inherited disorder characterized by impaired tubular uric acid transport, reabsorption insufficiency and /or acceleration of secretion. The affected individuals are predisposed to nephrolithiasis and recurrent episodes of exercise-induced acute kidney injury. Type 1 is caused by dysfunctional variants in the SLC22A12 gene (URAT1), while type 2 is caused by defects in the SLC2A9 gene (GLUT9).