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Mucopolysaccharidosis type IVA is a rare autosomal recessive lysosomal storage disorder occurring worldwide in all ethnic groups. It is caused by biallelic variants in the GALNS gene (OMIM 612222). We report five cases of mucopolysaccharidosis type IVA with short stature and severe skeletal dysplasia. An optimized diagnostic strategy that combined enzymatic testing and genetic screening was applied. All the tested urine samples showed increased urinary glycosaminoglycan / creatinine ratios. In all five cases, the enzyme activity of galactosamine-6-sulfate sulfatase was pathologically decreased. Gene-targeted sequencing revealed a previously unreported homozygous c.139-12T>C variant of the GALNS gene in one patient and three previously reported missense variants in four patients; c.253T>C (p.Cys85Arg), c.626C>T (p.Ala209Val) and c.878C>T (p.Ser293Leu). Genetic studies not only confirm the diagnosis of mucopolysaccharidosis IVA, but also enable predicting the prognosis and facilitate genetic counseling. Enzyme replacement therapy is not available in Sri Lanka to date. However, the quality of life in these patients can be improved by a multidisciplinary approach.

BackgroundProteinuria is an important marker of kidney disease. Protein-creatinine ratio and proteinosmolality ratio in a spot urine sample have been proposed as alternatives to estimation of 24-hour urinary protein excretion in order to simplify sample collection and minimize errors due to incorrect sample collection. ObjectiveThe study aimed to estimate the validity of urine protein-osmolality ratio and urine proteincreatinine ratio in a random urine sample as predictive measures of 24-hour urinary protein excretion, in a paediatric population. Methods A cross sectional descriptive study was conducted among 85 children with kidney disease from the medical wards and nephrology clinic of the Lady Ridgeway Hospital and 56 healthy children aged 3-12 years. Twenty four-hour urine samples and spot urine samples were collected from each participant. Urine protein-osmolality ratio and urine protein-creatinine ratio in the spot urine sample were determined and compared with 24-hour urinary protein excretion. Data was analysed using SPSS statistical package. Standard descriptive methods (mean, median, standard deviation etc.) were used to describe the measured parameters. Receiver operator characteristic (ROC) curves were created using protein-osmolality ratio and protein-creatinine ratio as test variables, and 24-hour urinary protein excretion as the 'gold standard' variable. Optimum cut-off values, maximizing sensitivity and specificity, for protein-osmolality ratio and protein-creatinine ratio were determined using ROC curves. ResultsThe optimal value discriminating normal from abnormal protein excretion was determined to be a protein-osmolality ratio of 0.38mg/L:mOsm/kgH 2 O (sensitivity 85.7%, specificity 100%) and a protein-creatinine ratio of 28mg:mmol (sensitivity 100%, specificity 94%). The cut-off value for discriminating mild from nephrotic proteinuria was a protein-osmolality ratio of 2.00 mg/L:mOsm/kgH 2 O (sensitivity 91.5%, specificity 100%) and a protein-creatinine ratio of 186 mg:mmol (sensitivity 93%, specificity 98.5%). Conclusions Both the protein-creatinine ratio and the protein-osmolality ratio in a spot urine sample can be used to determine nephrotic proteinuria. Urine protein-creatinine ratio was more sensitive than urine protein-osmolality ratio in detecting patients with mild proteinuria.

Introduction: Glomerular filtration rate (GFR) is used as a measure of overall renal function. Creatinine clearance (CrCl) based estimation of GFR requires a 24-hour collection of urine which is cumbersome and time consuming. Instead, Schwartz formula is used for the estimation of GFR based on calculations. It is an estimate of GFR (eGFR) in children, derived from body length (L, in cm), serum creatinine (Scr, in mg/dL) and a constant (k = 0.55): GFR = (0.55 × L) /Scr. However, it is important to cross validate this equation before using it in Sri Lankan children. Objective: To cross validate the use of Schwartz formula against CrCl, in a paediatric population in determining the glomerular function. Method: A cross-sectional descriptive study was carried out at Lady Ridgeway Hospital for Children, Colombo, Sri Lanka. Forty seven children with chronic kidney disease from medical wards and nephrology clinic and 26 healthy children, between the ages of 3-12 years were recruited. In these patients GFR was determined using CrCl and calculated GFR by Schwartz formula using serum creatinine measure. The CrCl values were compared against eGFR derived from Schwartz formula. Correlation and limits of agreement between the two methods were evaluated. Results: Although a weak but statistically significant correlation (r = 0.476, P<0.001) was observed between GFR determined by CrCl and that estimated by Schwartz formula in the whole _________________________________________