Autosomal Recessive Limb-Girdle Muscular Dystrophy-3: A Case Report of a Patient with Autism Spectrum Disorder.

Limb-girdle muscular dystrophies are a group of genetic disorders classically manifesting with progressive proximal muscle weakness. Affected individuals present with atrophy and weakness of the muscles of the shoulders and hips, and in some cases, intellectual disability or developmental delay has also been reported. Limb-girdle muscular dystrophy-3 is a recessive disorder caused by biallelic variants in the SGCA gene. Similarly, symptoms include proximal muscle weakness, elevated CPK, calf muscle pseudohypertrophy, and mobility issues. Cardiac symptoms and respiratory insufficiency are also common symptoms. This case report details a 3-year-old male with muscular weakness, elevated CK, and a neurodevelopmental disorder in whom a homozygous missense variant in c.229C>T (p.Arg77Cys) associated with limb-girdle muscular dystrophy-3 was found. This report shows the association between SGCA c.229C>T and neurodevelopmental disorders as observed in other muscular dystrophies.

Pediatric reference intervals for clinical chemistry assays on Siemens ADVIA XPT/1800 and Dimension EXL in the CALIPER cohort of healthy children and adolescents.

INTRODUCTION: Accurate reference intervals (RIs) are essential for clinical interpretation of laboratory test results; however, major gaps exist in pediatric RIs. The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) has established age- and sex-specific pediatric RIs on various analytical platforms. The current study expands the CALIPER database by establishing age- and sex-specific RIs for biochemical assays on Siemens ADVIA XPT/1800 and Dimension EXL Systems. METHODS: Serum samples from a total of 909 and 867 healthy children and adolescents (ages 0-<19 y) were tested on ADVIA XPT/1800 and Dimension EXL systems, respectively. Age- and/or sex-specific RIs were calculated for a total of 54 biochemical assays. RESULTS: Serum concentrations of several biomarkers remained relatively constant across the pediatric age range and similar between sexes, including sodium and triglycerides. Other biomarkers, such as alkaline phosphatase and creatinine showed both age and sex differences. Furthermore, immunoglobulin A and iron showed only age differences. DISCUSSION: We established RIs for creatine kinase, random glucose, total iron binding capacity, and several electrolytes for the first time using the CALIPER cohort. Overall, pediatric RIs established in the current study will allow for more accurate laboratory test interpretation worldwide using Siemens chemistry assays.

CLSI-based transference and verification of CALIPER pediatric reference intervals for 29 Ortho VITROS 5600 chemistry assays.

BACKGROUND: Evidence-based reference intervals (RIs) are essential to accurately interpret pediatric laboratory test results. To fill gaps in pediatric RIs, the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) project developed an age- and sex-specific pediatric RI database based on healthy pediatric subjects. Originally established for Abbott ARCHITECT assays, CALIPER RIs were transferred to assays on Beckman, Roche, Siemens, and Ortho analytical platforms. This study provides transferred reference intervals for 29 biochemical assays for the Ortho VITROS 5600 Chemistry System (Ortho). METHODS: Based on Clinical Laboratory Standards Institute (CLSI) guidelines, a method comparison analysis was performed by measuring approximately 200 patient serum samples using Abbott and Ortho assays. The equation of the line of best fit was calculated and the appropriateness of the linear model was assessed. This equation was used to transfer RIs from Abbott to Ortho assays. Transferred RIs were verified using 84 healthy pediatric serum samples from the CALIPER cohort. RESULTS: RIs for most chemistry analytes successfully transferred from Abbott to Ortho assays. Calcium and CO2 did not meet statistical criteria for transference (r2<0.70). Of the 32 transferred reference intervals, 29 successfully verified with approximately 90% of results from reference samples falling within transferred confidence limits. Transferred RIs for total bilirubin, magnesium, and LDH did not meet verification criteria and are not reported. CONCLUSIONS: This study broadens the utility of the CALIPER pediatric RI database to laboratories using Ortho VITROS 5600 biochemical assays. Clinical laboratories should verify CALIPER reference intervals for their specific analytical platform and local population as recommended by CLSI.