Establishment of Age Specific Reference Interval for Aminoacids and Acylcarnitine in Dried Blood Spot by Tandem Mass Spectrometry.

The Extended Screening for Inborn Errors of Metabolism is done for aminoacidopathies, fatty acid oxidation disorders and organic acid disorders. In a single dried blood spot, the tandem mass spectrometry is capable of measuring multiple analytes like amino acids, acylcarnitines, nucleosides, succinylacetone and lysophosphatidylcholines. This study was proposed to establish age specific reference internal for aminoacids and acylcartinitine in dried blood spot by tandem mass spectrometry. A total of 480 apparently healthy children were enrolled for the study and sub classified into four groups as follows: Group A: 0-1 month, Group B: 1 month-1 year, Group C: 1-5 year and Group D: 5-12 years each having 120 participants. Sample size were calculated as per CLSI approved guidelines. Tables 1 and 2 presents the age-specific percentile distribution of aminoacids and acylcarnitines established from healthy subjects as per rank-based method recommended by the IFCC and CLSI. Tables 3, 4 and 5 presents the cut-off values of primary and secondary marker/ratios for screening of aminoacidopathies, fatty acid oxidation disorders and organic acid disorders respectively. As a general principle, the interpretation of extended newborn screening results should be based on age specific cut-off established by the laboratory for primary analyte concentration and secondary analyte concentration/ ratios. This study was useful in establishing age specific cut-off values for various amino acids and acylcarnitines in South Indian population. [Table: see text] [Table: see text] [Table: see text] [Table: see text] [Table: see text].

A Case of Renal Tubular Acidosis with Sjogren's Syndrome Showing Paradoxical Block of PTH Due to Severe Hypomagnesemia.

Distal renal tubular acidosis (RTA) manifests either as Complete/Classical form or Incomplete/Latent Form. Distal RTA causes normal anion gap metabolic acidosis and hypokalemia. Interstitial Nephritis is the most frequent renal manifestation of Sjogren's, which presents as Distal RTA in 25-40% of patients with Sjogren's syndrome. Magnesium deficiency is frequently associated with hypokalemia. Although serum calcium is the main physiological control for the secretion of parathyroid hormone (PTH) by the parathyroid, serum magnesium can also exert similar effects. While low levels of magnesium stimulate the secretion of PTH, very low serum concentrations tend to induce a paradoxical block of PTH release by activation of the alpha-subunits of heterotrimeric G-proteins. This mimicks the activation of calcium sensing receptor leading to inhibition of PTH secretion. Here we describe the case history of a 35-year-old lady who presented to our hospital with severe hypokalemia due to distal RTA and perhaps had a paradoxical block of PTH secretion in the setting of severe hypomagnesemia.

Sigma metrics as a tool for evaluating the performance of internal quality control in a clinical chemistry laboratory.

OBJECTIVE: Six Sigma is one of the most popular quality management system tools employed for process improvement. The Six Sigma methods are usually applied when the outcome of the process can be measured. This study was done to assess the performance of individual biochemical parameters on a Sigma Scale by calculating the sigma metrics for individual parameters and to follow the Westgard guidelines for appropriate Westgard rules and levels of internal quality control (IQC) that needs to be processed to improve target analyte performance based on the sigma metrics. MATERIALS AND METHODS: This is a retrospective study, and data required for the study were extracted between July 2015 and June 2016 from a Secondary Care Government Hospital, Chennai. The data obtained for the study are IQC - coefficient of variation percentage and External Quality Assurance Scheme (EQAS) - Bias% for 16 biochemical parameters. RESULTS: For the level 1 IQC, four analytes (alkaline phosphatase, magnesium, triglyceride, and high-density lipoprotein-cholesterol) showed an ideal performance of ≥6 sigma level, five analytes (urea, total bilirubin, albumin, cholesterol, and potassium) showed an average performance of <3 sigma level and for level 2 IQCs, same four analytes of level 1 showed a performance of ≥6 sigma level, and four analytes (urea, albumin, cholesterol, and potassium) showed an average performance of <3 sigma level. For all analytes <6 sigma level, the quality goal index (QGI) was <0.8 indicating the area requiring improvement to be imprecision except cholesterol whose QGI >1.2 indicated inaccuracy. CONCLUSION: This study shows that sigma metrics is a good quality tool to assess the analytical performance of a clinical chemistry laboratory. Thus, sigma metric analysis provides a benchmark for the laboratory to design a protocol for IQC, address poor assay performance, and assess the efficiency of existing laboratory processes.

Retrospective Comparison of Estimated GFR using 2006 MDRD, 2009 CKD-EPI and Cockcroft-Gault with 24 Hour Urine Creatinine Clearance.

INTRODUCTION: The assessment of Glomerular Filtration Rate (GFR) is essential for clinical practice in assessing kidney function, drug dosing, detecting and estimating the prognosis of Chronic Kidney Disease (CKD). The most common practical method for assessing GFR is performed with a 24 hour/timed urine collection for creatinine clearance evaluation. The estimation of eGFR by creatinine based formulae is known to be a rapid and reliable means of approximation of creatinine clearance. AIM: To compare eGFR using three commonly used Formulae {Modification of Diet in Renal Disease Study Equation (MDRD 2006), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI 2009) and Cockcroft-Gault Formula} with 24 hour creatinine clearance and to identify which amongst the 3 formulae for eGFR closely correlates with 24 hour creatinine clearance in a secondary care hospital. MATERIALS AND METHODS: We retrospectively collected laboratory data requested for 24 hour creatinine clearance in the period from January 2014 to August 2016. Totally 91 laboratory request for 24 hour creatinine clearance data were obtained. The paired-t-test was used for comparison since all parameters used in the study were numerical, all patients came from same population and all had paired results. RESULTS: The eGFR by MDRD formulae had a statistically insignificant p-value (p > 0.05) i.e., good approximation in the IInd, IIIrd, IVth and Vth stages of CKD on comparison with 24 hour creatinine clearance. The eGFR by CKD-EPI formulae had a statistically insignificant p-value (p > 0.05) in the IInd, IVth and Vth stages of CKD. The eGFR by Cockcroft-Gault Formulae had a statistically insignificant p-value (p > 0.05) in the Ist, IInd and Vth stages of CKD. CONCLUSION: The Creatinine based GFR estimation provides a more accurate assessment of 24 hour creatinine clearance and kidney function than measuring serum creatinine alone but have certain limitations in few clinical circumstances. No single equation will be optimal for all populations. But the result of this study showed MDRD 2006 formulae to be more accurate than CKD-EPI 2009 and Cockcroft-Gault formulae in estimating GFR, detection of CKD, drug dosing and estimating prognosis.

Incidental Identification of Possible Delta-Beta Thalassemia Trait in a Family: A Rare Cause of Elevated Hb F.

Delta-Beta thalassaemia is an unusual variant of thalassaemia with elevated level of foetal haemoglobin (HbF). The clinical presentation of delta-beta thalassaemia is mild in both heterozygote and homozygote cases. We hereby describe a rare cause of elevated Hb F in a father and his two daughters. A 52-year-old diabetic male patient, on evaluation of chromatogram of cation exchange HPLC for HbA1c, we incidentally identified elevated Hb F of approximately 20%. Haematological investigation of the patient revealed decreased haemoglobin, normal RBC, leucocyte and platelet count, decreased MCV and MCH. Red cell morphology showed predominantly normocytic normochromic cells with mild anisopoikilocytosis, few microcytes and hypochromic cells seen. His liver function test was normal. Haemoglobin variant analysis revealed decreased Hb A (79.4%), normal Hb A2 (2%) and increased Hb F (19.75%). A possible diagnosis of heterozygous δ ß-thalassaemia was considered. Since most laboratories perform HbA1c by cation exchange HPLC method, a careful evaluation of the chromatogram yields useful information. In our case, the elevated Hb F in a father and further careful evaluation of clinical and haematological parameters in the family members made us to possibly think of rare disorders like heterozygous Delta-Beta thalassaemia in the family and provide valuable genetic counseling.