Inappropriate supplementation of Vitamin D can result in toxicity: a crosssectional study of paediatrics population.

OBJECTIVE: To evaluate children with suspected or definite hypervitaminosis D with respect to prevalence, clinical manifestations and pharmacological aspects. METHODS: The retrospective cross-sectional study was conducted at the Aga Khan University Hospital, Karachi, and comprised medical records from January 1 to December 31, 2018, of children aged <18 years with 25-hydroxyvitamin D levels >50ng/ml. Clinical and pharmacological data was retrieved. Data was analysed using SPSS 23. RESULTS: Of the 118,149 subjects visiting the clinical laboratory during the study period, children tested for serum 25-hydroxyvitamin D levels were 16,316(13.8%) who had a median age of 9.78 years (interquartile range: 10.2 years). Children who registered for consultation were 2720(16.6%), and, out of them, 602(22%) had serum 25-hydroxyvitamin D >50ng/ml. The median 25-hydroxyvitamin D levels and age were 70.1ng/ml (interquartile range: 100ng/ml) and 3.1 years (interquartile range: 17.93 years), respectively, and 345(57.3%) of them were boys. Children supplemented with vitamin D were 197(33.1%) and 193(97.9%) of them were prescribed by physicians. Mega-doses were taken by 68(34.17%), while the remaining had used various combinations in syrup or tablet forms. Commonly prescribed mega-doses were 600,000IU 30((44.1%) and 200,000IU 31(45.5%) injections of vitamin D. The primary indications were pains/aches in 51(25.8%) cases, developmental delay 50(25.3%), and vitamin D deficiency 49(24.8%). The main symptoms of hypervitaminosis D or toxicity were abdominal pain 27(13.7%) and constipation 31(15.7%). CONCLUSIONS: Children should be given vitamin D supplements with caution as prolonged supplementation and repeated mega-doses can result in toxicity which may cause serious consequences.

Evaluation of CSF kappa free light chains for the diagnosis of multiple sclerosis (MS): a comparison with oligoclonal bands (OCB) detection via isoelectric focusing (IEF) coupled with immunoblotting.

This study was done to evaluate the diagnostic accuracy of cerebrospinal fluid kappa free light chain (KFLC) for diagnosis of multiple sclerosis, against isoelectrofocusing (IEF) to detect oligoclonal bands (OCB) as gold standard. 64 cases were divided into positive and negative based on the OCB results. Diagnostic accuracy was calculated for the 1 mg/L cut-off. The 1 mg/L cut-off yielded a percent agreement of 86.1% and Cohen's kappa value of 0.8. Youden's index, yielded a cut-off of 0.92 mg/L as optimal (90.3% specificity and 90.9% sensitivity). The analytical time was 3 hours and 55 min for IEF and 25 min for KFLC. The cost of a single OCB test was PKR12 000 (US$68.17) compared with PKR4150 (US$23.58) for KFLC. KFLC proved to be an accurate, cheaper and time-saving alternative and can be performed prior to the contemporary testing.

Biotin-responsive Multiple Carboxylase Deficiency (MCD).

This study aimed to determine the clinical spectrum and biochemical findings on urine organic acids (UOA) in Biotin-responsive multiple carboxylase deficiency (MCD) patients presenting to the biochemical genetics laboratory (BGL). Patients reported as MCD, from January 2013-December 2020 were included. The UOA was analysed by gas chromatography mass spectrometer. Demographic, clinical, and biochemical details were extracted from the BGL history form. Two hundred and two patients were reported to have biotin responsive MCD with 111(55%) males and a median (Q3-Q1) age of 7 months (13-4). Of these 71.7% (n=145) patients presented in infantile period. Parental consanguinity was observed in 80% (n=161) and another 32.6% (n=66) cases grandparents were cousins. The main presenting features were seizures, developmental delay, and lethargy. The common peaks were determined on UOA 3OHIVA, MC and MCC. MCD is not rare in Pakistani population; it is recommended to include this disorder in newborn screening programs. Key Words: Biotin responsive multiple carboxylase deficiency, Organic acids, Amino acids, Pakistan, Inborn errors of metabolism.

Practices of vitamin D supplementation leading to vitamin D toxicity: Experience from a Low-Middle Income Country.

INTRODUCTION: The trend of prescribing VD preparations for nonspecific body aches and self-medication has increased significantly. The importance of vitamin D toxicity (VDT) has been underestimated and under recognized. This study was done to determine the frequency toxicity (>150 ng/ml) in subjects for 25-hydroxyvitamin D (25OHD) and evaluate the vitamin D (VD) supplements used by these subjects. METHODOLOGY: This descriptive cross-sectional study was conducted at the Section of Chemical Pathology, Aga Khan University Hospital Karachi from April 2020 to March 2021. Subjects with 25OHD toxicity were contacted and information related to history of calcium and VD supplementation were collected. The statistical analysis was performed using the Microsoft Excel 2016. RESULTS: Over a year period 105398 subjects were tested for serum 25OHD, of which 0.34% (n = 364) subjects had 25OHD level of >150 ng/ml. After satisfying exclusion criteria 186 subjects (78 were <18 years of age and 108 were adults) were included in final analysis. All of these were using VD supplements and the main indications were delayed growth/short height (43.7%, n = 34) and aches or pains in (54.6%, n = 59) in pediatric and adult subjects respectively.Most of the subjects were taking supplements orally (74.1%, n = 138). Commonly prescribed preparation in adults and pediatric was 200,000 IU (70.4%, n = 76) and 400 IU (35.9%, n = 28) respectively. Most subjects took supplements for 1-3 months (68.3%, n = 127). Stated total supplementation ranged from 20,000 IU to 3600,000 IU in pediatric subjects and 200,000 IU to 96,00,000 IU in adults. CONCLUSIONS: Supplementation is a leading cause of potential toxic levels of 25OHD. The condition can be prevented by careful use of VD supplements and consistent monitoring.

Establishing reference interval for thyroid-stimulating hormone in children below two-year ages in Pakistani population.

INTRODUCTION: Reference intervals (RIs) of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) are age, assay and population specific. Currently, the age and assay-specific RIs for TSH are not available for children under two years of age. This study aimed to establish reference intervals for serum concentrations of TSH and FT4 in healthy children aged 1-24 months as per CLSI C28-A3 guidelines. METHODS: This prospective cross-sectional study was conducted in children from 1 to 24 months visiting the clinical laboratory for serum vitamin D testing but without any recent illness, hospitalization, medication and history of maternal thyroid diseases from August 2018 to March 2019 were invited to participate in the study.Serum TSH and FT4 were measured on ADVIA Centaur (Siemens Diagnostics, US), using chemiluminescence immunoassay. Kolmogorov-Smirnov test assessed normality of the data and RIs based on central 95% of the population were established using the non-parametric approach. RESULTS: After excluding one subject with confirmed congenital hypothyroidism, a total of 131 children were included in the study. The median (IQR) age of the study subjects was 12 months (11), and majority 78 (59.5%) were boys. The RIs were established using non-parametric approach as the data was not normally distributed. Reference interval for TSH was 0.73-4.94 µIU/mL and for FT4 was 0.81-1.51 ng/dl. CONCLUSION: We established assay-specific RIs for serum TSH and FT4 in children aged 1-24 months in our population. The RIs were slightly lower from RIs developed on other platforms in different population.