Clinical, biochemical, and molecular profiles of three Sri Lankan neonates with pyruvate carboxylase deficiency.

Objectives: Pyruvate carboxylase, a mitochondrial enzyme, catalyses the conversion of glycolytic end-product pyruvate to tricarboxylic acid cycle intermediate, oxaloacetate. Rare pyruvate carboxylase deficiency manifests in three clinical and biochemical phenotypes: neonatal onset type A, infantile onset type B and a benign C type. The objective of this case series is to expand the knowledge of overlapping clinical and biochemical phenotypes of pyruvate carboxylase deficiency. Case presentation: We report three Sri Lankan neonates including two siblings, of two unrelated families with pyruvate carboxylase deficiency. All three developed respiratory distress within the first few hours of birth. Two siblings displayed typical biochemical findings reported in type B. The other proband with normal citrulline, lysine, moderate lactate, paraventricular cystic lesions, bony deformities, and a novel missense, homozygous variant c.2746G>C [p.(Asp916His)] in the PC gene, biochemically favoured type A. Conclusions: Our findings indicate the necessity of prompt laboratory investigations in a tachypneic neonate with coexisting metabolic acidosis, as early recognition is essential for patient management and family counselling. Further case studies are required to identify overlapping symptoms and biochemical findings in different types of pyruvate carboxylase deficiency phenotypes.

Students' perceptions of online education: A session at the FAOBMB-IUBMB-CBSL virtual education symposium 2021.

The Federation of Asian and Oceanian Biochemists and Molecular Biologists (FAOBMB) and the College of Biochemists of Sri Lanka (CBSL) organized a virtual education symposium in 2021 funded by the International Union of Biochemistry and Molecular Biology (IUBMB). The parallel session named "Students' Perception" was attended by 188 participants from 11 countries. The main objectives of this session were to aggregate participants' viewpoints on aspects of virtual education, including innovative strategies to enhance motivation and engagement of students, improving teacher-student and student-student interactions, managing stress, and virtual learning platforms. Data were collected via rapporteurs from multiple segments of the session including a mini-introductory talk, poll, role play, and discussions about outstanding student experiences, types of virtual platforms, innovative methods of teaching, student motivation and stress management. The importance of student perception and issues like technological difficulties and the reluctance of students to engage were discussed. In addition to well-established strategies such as using polls, chat box features, and discussions in breakout rooms, participants also proposed exciting learning methods to engage students such as quizzes, competitions and challenges, engagement of multiple sensory modalities, story-based learning, and so forth. This report provides anecdotal evidence on pedagogies described in textbooks and also introduces new ideas based on this existing foundation. Future research should aim to harmonize virtual education with traditional classroom methods and explore innovative virtual tools like avatar-based universities, virtual labs, and user-friendly online assessment platforms. The results apply to all disciplines, and not exclusively to biochemistry and molecular biology (BMB).

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 LPIN1 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. These episodes were triggered by infections and exercise. A temporal relationship between the acute episodes and use of drugs such as theophylline, mefenamic acid, co-trimoxazole, and combined oral contraceptive pills was also noted. There was marked elevation of serum creatine kinase and transaminases during acute episodes. Family history revealed parental consanguinity and an affected sibling who died of an acute episode associated with muscle weakness, dark coloured urine, and cyanosis, at the age of 2 years. The histochemical findings of the patient under discussion were consistent with a metabolic myopathy affecting membrane integrity. A homozygous, likely pathogenic variant c.1684G>T encoding p.(Glu562∗) was identified by clinical exome sequencing. Even though the studies to date give no convincing evidence of a possible causal or contributory relationship between the drugs under discussion and lipin-1 related rhabdomyolysis, this case highlights the importance of pharmacovigilance and reporting adverse drug reactions in patients with lipin-1 deficiency.

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. The most common phenotypic features in this sample of symptomatic patients were persistent or recurrent lower respiratory tract infections, failure to thrive and Pseudo-Bartter syndrome. Altogether 7 cystic fibrosis causing mutations were identified in 10 patients. Except delta F508 which is the commonest mutation worldwide all the other mutations detected in Sri Lankan patients are rare mutations. 1161delC and V456A detected in our patients are South Asian mutations. The other mutations such as [C.1282C > G; C.2738A > G], C.53 + 1G > C, 2184insA and a deletion encompassing exons 4 to 11 have been reported previously from European patients with cystic fibrosis. CONCLUSION: These cases highlight the importance of considering the diagnosis of cystic fibrosis in children and young adults presenting with persistent respiratory tract infections associated with severe malnutrition and Pseudo-Bartter syndrome, especially in low income countries where newborn screening for cystic fibrosis is not available. The spectrum of CFTR mutations in Sri Lanka is heterogeneous and possibly linked to genetic flow from Indian subcontinent and Europe. The common mutations should be identified by sequencing the entire CFTR gene in adequate number of cystic fibrosis patients in order to design a mutation panel for common regional mutations.

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

BACKGROUND: Uric 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 1: A 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 2: An 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 3: A 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 4: A 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. CONCLUSION: Abnormal 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.