Children with lysinuric protein intolerance: Experience from a lower middle income country.

BACKGROUND: Lysinuric protein intolerance (LPI) is an inborn error of metabolism consequential to recessive mutations in the SLC7A7 gene. The metabolic imbalance in absorption and excretion of dibasic amino acids is considered the basis of LPI. The disease results from protein intolerance with signs and symptoms oscillating from cerebral impairment, respiratory involvement, renal failure and autoimmune complications. AIM: To determine biochemical and clinical presentation of cases with biochemical picture suggestive of LPI in Pakistani children. METHODS: The study was conducted at the Biochemical Genetic Lab, Department of Pathology and Laboratory Medicine, AKU Plasma, and urine amino acid quantification data from January 2013 to October 2018 was included in this study. The amino acids were analyzed by high performance liquid chromatography. Prestructured requisition forms were used to obtain the clinicopathological data. Statistical analysis was done by Microsoft Excel 2017. RESULTS: A total of 6 patients were recognized. All the patients were male (100%). The mean age was 24 mo ± 10 d. All the patients had low plasma concentration of lysine, ornithine and arginine, whereas increased levels of lysine, ornithine and arginine in urine were observed in 2 patients. History of consanguineous marriage was present in all patients (100%). The most observed clinical symptom was feeding difficulty followed by failure to thrive (83.3%) and developmental delay (66.6%). Hepatomegaly was present in all patients (100%). No mutation analysis was done. CONCLUSION: This study portrays the biochemical and clinical spectrum of LPI in Pakistan. Although clinical manifestations appeared in the first 2 years of life, most of them suffered a delay in undergoing diagnostic workup.

Spectrum of Cystic Fibrosis Conductance Regulator Gene Mutations Reported in Pakistani Descent Cystic Fibrosis Patients.

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This study aims to determine the genotypic and phenotypic spectrum of the CFTR gene mutations reported in the literature for Pakistani-origin CF patients. Databases were searched for such studies from 1947-2019 for sample size, method of diagnosis, and CFTR gene mutations. The authors identified 12 studies reporting 33 CFTR gene mutations, both intronic as well as exonic in Pakistani origin patients. The most widely tested mutation was D508 with a frequency of 17%-60%. No hotspot zone was identified and not all reported mutations were causing disease. There is a need to identify common mutations in the Pakistani population to develop population-specific CFTR mutations panel. This will enable the researchers to perform phenotype-genotype correlation studies to improve the CF detection rate. Key Words: Cystic fibrosis, Pakistan, Mutations, CFTR.

Determination of reference interval (RI) of spot urinary oxalate to creatinine ratio in children of pakistani origin under six years of age: A cross-sectional study.

BACKGROUND: The gold standard screening method of hyperoxaluria in children is using 24-hour urine collection. Urine collection may be cumbersome and challenging for children. Reference intervals (RI) of oxalate for the Pakistani population are not readily available. Therefore we aimed to determine the oxalate to creatinine ratio (Ox: Cr) for Pakistani children <6 years of age. MATERIALS AND METHODS: A cross-sectional study was conducted at Aga Khan University from June 2018 to October 2019. Random urine samples from apparently healthy children < 6 years were collected and stored at -30°C until analysis after adding 6M HCl. Oxalate was measured on Micro lab 300 using a kit based on oxalate oxidase principle, while creatinine was measured by kinetic Jaffe reaction. Data was analyzed by EP evaluator and SPSS 23. Ox: Cr ratio was calculated and reported with 90% confidence interval (CI) and interquartile range (IQR). RESULTS: The mean age of study subjects (n=120) was 29 ±22.3 months with an M: F ratio of 1:1. Children of various ethnicities were included from all over Karachi. The majority of the subjects were Urdu speaking (37.5%). Median Ox: Cr was 0.13(0.10). No significant difference was noted in the median Ox: Cr ratio between various ethnicities (p>0.05). It was significantly different in group I to V which was 0.25 (IQR: 0.06), 0.19 (IQR: 0.11), 0.15 (IQR: 0.04), 0.11 (IQR: 0.06) and 0.08 (IQR: 0.04) respectively (pvalue <0.001). CONCLUSION: The established RIs of Ox: Cr ratio was 0.05-0.34 (90% CI). Ox: Cr ratio showed a declining trend with age. Large scale reference interval studies are encouraged, taking diet and age into consideration.

Relationship of spot urine oxalate to creatinine ratio and 24 hours urinary oxalate excretion in patients with urolithiasis.

BACKGROUND: The evaluation of 24 h urinary oxalate excretion is the gold standard for diagnosing hyperoxaluria in patients with recurrent urolithiasis. However, 24 h urine sample collection is cumbersome. Therefore we aim to see if oxalate to creatinine ratio in random urine sample can be used as an alternative. MATERIALS AND METHODS: A cross-sectional study was conducted at Section of Chemical Pathology, Department of Pathology and Laboratory Medicine Aga Khan University Karachi from 1st February to December 31, 2019. A total of 62 adult patients, 18-60 years of age with history of kidney stones presenting to the clinical laboratory for 24 h urine oxalate estimation were invited to participate in the study after informed consent. Clinical details were recorded on a structured questionnaire and patients were guided to submit 24 h urine and a random spot urine sample. Urinary oxalate was measured on Micro lab 300 using a kit based on oxalate oxidase principle by Trinity Biotech plc, Wicklow, Ireland following standard operating procedures. Urinary creatinine was measured on ADVIA 1800 by Siemens, US using kinetic Jaffe reaction according to the manufacturer's instructions. The data was analyzed on SPSS. RESULTS: In a period of ten months, a total of 62 subjects were recruited; mean age was 32.4 ± 2.6 years. Males were 49 (79.0%) and females were 13 (20.9%). Correlation was found to be (r = 0.289) by Spearman correlation (p value < 0.005). Taking 24 h urinary oxalate as gold standard the sensitivity, specificity, positive predictive value and negative predictive value of spot oxalate to creatinine ratio was 83.3%, 17.8%, 9.8% and 90.9% respectively. CONCLUSION: The random spot urine test cannot replace the 24 h urinary oxalate estimation in patients with urolithiasis.