Rare and heterogeneous manifestations of leucocyte adhesion deficiency type 1: report of two cases with diagnostic dilemmas and novel ITGB2 mutation.

BACKGROUND: Primary immunodeficiency disorders (PID) are rare disorders with heterogeneous manifestations, overlapping with other diseases such as autoimmunity, malignancy, and infections. This makes the diagnosis very challenging and delays management. Leucocyte adhesion defects (LAD) are a group of PIDs in which patients lack adhesion molecules on leukocytes needed for their emigration through blood vessels to the site of infection. Patients with LAD can present with diverse clinical features including severe and life-threatening infections, early in life, and the absence of pus formation around infection or inflammation. There is often delayed umbilical cord separation, omphalitis, late wound healing, and a high white blood cell count. If not recognized and managed early, can lead to life-threatening complications and death. CASE PRESENTATION: LAD 1 is characterized by homozygous pathogenic variants in the integrin subunit beta 2 (ITGB2) gene. We report two cases of LAD1 with unusual presentations (post-circumcision excessive bleeding and chronic inflammation of the right eye) which were confirmed by flow cytometric analysis and genetic testing. We found two disease-causing ITGB2 pathogenic variants in both cases. CONCLUSIONS: These cases highlight the importance of a multidisciplinary approach to recognizing clues in patients with uncommon manifestations of a rare disease. This approach initiates a proper diagnostic workup of primary immunodeficiency disorder leading to a better understanding of the disease, and appropriate patient counseling, and helps clinicians to be better equipped to deal with complications.

Calculus anuria: a urological emergency with an excellent outcome.

Calculus anuria is a catastrophic condition with dire consequences if not treated promptly. The purpose of this study was to identify factors which influence the short-term outcome of patients with calculus anuria. A retrospective analysis was conducted from January 2016 to December 2021, in children up to the age of 18 years, who presented with calculus anuria and required emergency decompression at Sindh Institute of Urology and Transplantation, Pakistan. One hundred and twenty-five children were included. Majority were born to consanguineous parents and a few of them had positive family history of stone disease. Severe illness was found in 25 (20%) patients and among them 8 (32%) required hemodialysis. Decompression by double J stenting is the preferred intervention in our institute and was done in 106 (85%) children, followed by percutaneous nephrostomy tube in 10 (8%) successfully. A small number of patients, 9 (7%) required both procedures to relieve their obstruction. A significant number of patients, about 115 (92%), attained normal renal functions after intervention. No pertinent factors were identified, relating to incomplete renal recovery in nine (7%) of the patients who unfortunately progressed to chronic kidney disease.

Primary hyperoxaluria: Comprehensive mutation screening of the disease causing genes and spectrum of disease-associated pathogenic variants.

The primary hyperoxalurias are rare disorders of glyoxylate metabolism. Accurate diagnosis is essential for therapeutic and management strategies. We conducted a molecular study on patients suffering from recurrent calcium-oxalate stones and nephrocalcinosis and screened primary hyperoxaluria causing genes in a large cohort of early-onset cases. Disease-associated pathogenic-variants were defined as missense, nonsense, frameshift-indels, and splice-site variants with a reported minor allele frequency <1% in controls. We found pathogenic-variants in 34% of the cases. Variants in the AGXT gene causing PH-I were identified in 81% of the mutation positive cases. PH-II-associated variants in the GRHPR gene are found in 15% of the pediatric PH-positive population. Only 3% of the PH-positive cases have pathogenic-variants in the HOGA1 gene, responsible to cause PH-III. A population-specific AGXT gene variant c.1049G>A; p.Gly350Asp accounts for 22% of the PH-I-positive patients. Pathogenicity of the identified variants was evaluated by in-silico tools and ACMG guidelines. We have devised a rapid and low-cost approach for the screening of PH by using targeted-NGS highlighting the importance of an accurate and cost-effective screening platform. This is the largest study in Pakistani pediatric patients from South-Asian region that also expands the mutation spectrum of the three known genes.

Association Of Bone Mineral Profile With Restless Leg Syndrome In Patients With End Stage Renal Disease.

Background: Restless leg syndrome (RLS) is one of the problem hemodialysis patients may encounter. This study was done to find out the association of restless legs syndrome (RLS) in end stage renal disease patients with serum calcium, phosphorus and parathyroid hormone levels. Methods: This cross-sectional observational study was done at The Kidney Centre, postgraduate Training Institute Karachi, Pakistan from Jan to June 2020. One hundred and twelve patients on three per week hemodialysis for more than three months at our hemodialysis centre were face to face interviewed as per International Restless Legs Syndrome Study Group criteria (IRLSSG) for the presence of RLS symptoms. Their demographic data and laboratory values were recorded from history chart and computer records. The bone mineral profile in this study includes serum calcium (corrected for albumin), serum phosphate levels and serum intact Parathyroid hormone (iPTH) levels. Statistical analyses were done by using SPSS-21. Results: In our study, 38.4% patients had RLS. Serum phosphorus levels were significantly higher in patients with RLS as compared to those who didn't have RLS. No significant association of serum calcium and Parathyroid hormone (PTH) levels with RLS was found. Conclusion: There is a high prevalence of RLS in ESRD patients as compared to general population. Serum phosphorus levels need to be observed and corrected along with maintenance of calcium and PTH levels to improve symptoms of RLS in these patients.

Primary hyperoxaluria and genetic linkages: an insight into the disease burden from Pakistan.

Autosomal recessive disorders are prevalent in Pakistan, a developing South Asian country where consanguineous marriages are common. This study seeks to determine the prevalence of monogenic causes in children presenting with nephrocalcinosis and nephrolithiasis at a dialysis and transplant center in Karachi, Pakistan. A retrospective analysis was conducted in children aged 1-18 years presenting with nephrocalcinosis, between 2010 and 2019. Demographic information, clinical profile, laboratory parameters and stone analysis were collected, on a pre-designed questionnaire. One hundred and twenty-six children were included, with 11 and 3 diagnosed with renal tubular acidosis and Bartter's syndrome respectively. Next-generation sequencing and Sanger sequencing was performed on 112 children. Eighty-seven patients were diagnosed with primary hyperoxaluria, with mutations in alanine-glyoxylate-aminotransferase gene found in 73, followed by glyoxylate reductase/hydroxy-pyruvate reductase in 13, and 4-hydroxy-2-oxaloglutarate aldolase in 1. Twenty-five patients reported negative for mutations. Sixty-four percent were males, with a statistically significant difference (p < 0.05). History of parental consanguineous marriage was found in 98% of the cohort. Fifty-four and 40 patients presented to the clinic with Chronic Kidney Disease Stage 1 and Stage 5, respectively, with a statistically significant difference p = 0.007. Mutations noted in our cohort are different and more severe than those reported in the developed world. The disease poses a major disease burden in developing world context with the only treatment option of combined liver-kidney transplantation not available in Pakistan.

Guideline Adherence of Paediatric Urolithiasis: An EAU Members' Survey and Expert Panel Roundtable Discussion.

Background: Paediatric nephrolithiasis has increased globally, requiring standardized recommendations. This study aims to assess the paediatric urolithiasis care between EAU members along with the statements of three experts in this field. Methods: The results of an electronic survey among EAU members comparing the guideline recommendations to their current practice managing paediatric nephrolithiasis in 74 centres are contrasted with insights from an expert-panel. The survey consisted of 20 questions in four main sections: demographics, instrument availability, surgical preferences and follow-up preferences. Experts were asked to give insights on the same topics. Results: A total of 74 responses were received. Computerised Tomography was predominantly used as the main imaging modality over ultrasound. Lack of gonadal protection during operations was identified as an issue. Adult instruments were used frequently instead of paediatric instruments. Stone and metabolic analysis were performed by 83% and 63% of the respondents respectively. Conclusions: Percutaneous Nephrolithotomy is the recommended standard treatment for stones > 20 mm, 12% of respondents were still performing shockwave lithotripsy despite PNL, mini and micro-PNL being available. Children have a high risk for recurrence yet stone and metabolic analysis was not performed in all patients. Expert recommendations may guide clinicians towards best practice.

Mini Nutritional Assessment (MNA) as a Reliable Tool for Nutritional Assessment of Hemodialysis Patients: A Single-Center Observation.

Objective In this study, we evaluated mini nutritional assessment (MNA) as a tool for the assessment of the nutritional status of end-stage renal disease (ESRD) patients on maintenance hemodialysis (MHD). Methods This prospective cross-sectional study was done from February 2021 till August 2021 on ESRD patients on MHD at our center. Nutritional status was assessed by using MNA score which evaluates four different aspects: anthropometric measures (body mass index [BMI], weight loss, mid-arm and mid-calf circumferences); general assessment (lifestyle, medications, mobility, and signs of depression); short dietary assessment (number of meals, food, and fluid intake) and subjective assessment (self-perception of food and nutrition). Results Out of 195 study subjects, 127 (65.1%) were males and 68 (34.9%) were females. Most women were stay-at-home mothers (57, 29.2% overall and 83.8% among all women), while most men owned their own businesses (44, 22.6% overall). The mean age was 51.2±14 years and the mean duration of hemodialysis was 4.6±4.1 years. Most of our patients belonged to the middle socioeconomic group (110, 56.6%). By using MNA, we found that most are at risk of developing malnutrition (112, 57.4%); however, only 9 (4.6%) patients are malnourished. In our study group, most malnourished patients belonged to the age group of >65 years (5, 56.6%). BMI was found to be significantly associated with MNA (p <0.001). Conclusion MNA is an easy and reliable bedside tool that can be used in ESRD patients on MHD for nutritional assessment. This is helpful in nutritional planning and the prevention of malnutrition.

Assessment of the Nutritional Status of the Hemodialysis Patients by Anthropometric Measurements.

Objective This study assessed the nutritional status of end-stage renal disease (ESRD) patients on maintenance hemodialysis (MHD) by utilizing bedside anthropometric measurements. Methods This prospective cross-sectional study was done from November 2020 till April 2021 on ESRD patients three times a week MHD at our centre. Anthropometric measurements including body mass index (BMI), triceps skinfold thickness (TSFT), mid-arm circumference (MAC), calf circumference (CC) and handgrip strength (HGS) were measured mid-arm muscle circumference (MAMC) was calculated, and nutritional status was determined. Results Out of 195 patients recruited in our study, 127 (65.1%) were male. The mean age was 51.2 ± 14.8 years with a minimum of 20 and a maximum of 90 years, while the mean duration of HD was 4.6 ± 4.1 years. The majority of our patients had TSFT of 60 % to 90% 93 (47.7%), indicating mild to moderate depletion of fat stores and MAMC of >90 % 128 (65.6%), indicating good protein stores. Among all anthropometric measures, BMI was strongly associated with age (<0.001), while gender and duration of MHD were associated with TSFT (p <0.001). Conclusion Anthropometric measurements are easy and inexpensive bedside methods for assessing the nutritional status of ESRD patients on MHD. Our study concluded that our MHD patients have overall good nutritional status, though our young patients have low BMI and old have obesity. Male patients have weaker HGS. With the increased number of years on MHD, malnutrition increases. Our study will help to treat physicians and nutritionists for proper nutritional planning and implementation to prevent malnutrition.

Update on Surgical Management of Pediatric Urolithiasis.

Urolithiasis has always been a fascinating disease, even more so in children. There are many intriguing facets to this pathology. This article is a nonsystematic review to provide an update on the surgical management of pediatric urolithiasis. It highlights the pros and cons of various minimally invasive surgical options such as extracorporeal shockwave lithotripsy (ESWL), retrograde intrarenal surgery (RIRS), percutaneous nephrolithotomy (PCNL), laparoscopy, and robotics. This article also describes the various intracorporeal disintegration technologies available to fragment the stone, including the newer advancements in laser technology. It also emphasizes the cost considerations especially with reference to the emerging economies. Thus, this manuscript guides how to select the least-invasive option for an individual patient, considering age and gender; stone size, location, and composition; and facilities and expertise available.

Chemical Composition Of Stones In Paediatric Urolithiasis.

BACKGROUND: Chemical composition of stones is one of the important diagnostic criteria for aetiology of stone formation and treatment to prevent recurrence. This paper reports composition of stones in children at a tertiary hospital by Fourier Transformation Infrared Spectroscopy (FTIR). METHODS: Between January-June 2015, 412 urinary stones from children were analysed by FTIR. Chi-square tests were used for the comparison of categorical measurements between groups. All reported values were 2-sided and statistical significance was considered at p-value ≤0.05. RESULTS: Of the 412 stones, 263 (63.8%) were renal, 101(24.5%) bladder and 48 (11.7%) ureteric. The mean age of children was 7.15±4.13 years with a M:F ratio 2.4:1. Of the 412 stones, 144(34.9%) were pure stones composed of one compound and 268(65.1%) were mixtures. Frequency of compound in stones was Ammonium Acid Urate (AAU) (65%), Calcium Oxalate (CaOx) (76.9%), Uric Acid (5%), Calcium Phosphate Apatite (7%), Whitlockite (8.4%), Struvite (4%), Cystine (0.72%) and Xanthine (2.11%). Frequency of compounds analysed in three ages groups 0-5, 6-10 and 11-15 years showed high frequency of AAU (73%) in 0-5 years as compared to (60%) in 11-15 years (p<0.018). CaOx (90%) in 11-15 as compared to (62.5%) in 0-5 years (p<0.001). Bladder stones were more prevalent in children 0-5 years (32%) vs 19% in 11-15 years (p<0.004) while renal were 75% in 11-15 years and 54% in 0-5 years (p<0.04). CONCLUSIONS: AAU stones known to be associated with malnutrition and chronic diarrhoea are highly prevalent in paediatric stones formers in our population in the kidney, bladder and ureter.