Clinical and molecular characterization of a large primary hyperoxaluria cohort from Saudi Arabia: a retrospective study.

BACKGROUND: Primary hyperoxalurias (PHs) constitute rare disorders resulting in abnormal glyoxalate metabolism. PH-associated phenotypes range from progressive nephrocalcinosis and/or recurrent urolithiasis to early kidney failure. METHODS: A retrospective study was conducted for patients with confirmed PH diagnoses from three tertiary centers in Saudi Arabia. Detailed clinical molecular diagnosis was performed for 25 affected individuals. Whole exome sequencing (WES)-based molecular diagnosis was performed for all affected individuals. RESULTS: The male:female ratio was 52% male (n = 13) and 48% female (n = 12), and consanguinity was present in 88%. Nephrolithiasis and/or nephrocalcinosis were present in all patients. Kidney stones were present in 72%, nephrocalcinosis in 60%, hematuria in 32%, proteinuria in 16%, abdominal pain in 36%, developmental delay in 8%, and chronic kidney disease stage 5 (CKD stage 5) was observed in 28% of the patients. The most common PH disorder was type I caused by variants in the AGXT gene, accounting for 56%. The GRHPR gene variants were identified in 4 patients, 16% of the total cases. Seven patients did not reveal any associated variants. Missense variants were the most commonly observed variants (48%), followed by frame-shift duplication variants (28%). CONCLUSIONS: Characterization of the genetic and clinical aspects of PH in this unique population provides direction for improved patient management and further research. A higher resolution version of the Graphical abstract is available as Supplementary information.

Delineation of cystinuria in Saudi Arabia: A case series.

BACKGROUND: Cystinuria is an inherited metabolic disease that is caused by defects in two genes, SLC3A1 and SLC7A9, which result in a renal reabsorptive defect of cystine and other dibasic amino acids, including ornithine, arginine, and lysine. Patients usually present with recurrent renal calculi and may develop renal impairment. Medical management includes high fluid intake and chelating agents. To the best of our knowledge, this is the first study describing cystinuria in Saudi Arabia. METHODS: A retrospective chart review for cystinuria patients from the genetic and nephrology divisions between 2010 to 2015. All patients were investigated, diagnosed and treated at King Abdulaziz Medical City in Saudi Arabia. RESULTS: Eight patients were identified from five unrelated families. The age of onset ranged from birth to 14 years. The female to male ratio was 1.7:1. Two new variants in the SLC3A1 and SLC9A7 genes were discovered. All of the detected mutations were missense variants in three different exons, such as c.1711 T > A (p.Cys571Ser) (exon 10), c.1166C > T p.Thr389Met (exon 11) and c.1400 T > A p.Met467Lys (exon 8). Additionally, 37.5% of our patients developed arterial hypertension and 25% had urinary tract infection, but none had renal impairment. No significant clinical differences were detected in this study between type A (SLC3A1 variants) and type B cystinuria (SLC7A9 variant). Two cases were diagnosed based on clinical information, biochemical testing and a positive family history as all of the molecular testing for cystinuria was negative. CONCLUSION: Cystinuria has wide genetic heterogeneity with a poor genotype/phenotype correlation. Negative molecular investigations should not rule out the disease if clinical and biochemical investigations support the diagnosis. A larger data registry is essential to better describe the cystinuria genotype/phenotype in Saudi Arabia.

Acute Kidney Injury Secondary to Rhabdomyolysis: A Case of Child Physical Abuse.

Child abuse is a challenging problem that any healthcare worker might encounter. It can lead to multiple physical and psychological effects on the child. We report a case of an eight-year-old boy who presented to the emergency department with history of decreased level of consciousness and change in urine color. On examination, he was found to be jaundiced, pale, and hypertensive (160/90 mmHg) with multiple skin abrasions all over the body, suggestive of physical abuse. Laboratory investigations were consistent with acute kidney injury and significant muscle damage. The patient was admitted to intensive care unit (ICU) as a case of acute renal failure secondary to rhabdomyolysis, and subsequently required temporary hemodialysis during his stay in the ICU. The child protective team was involved in the case throughout his hospital admission. Rhabdomyolysis with acute kidney injury secondary to child abuse is an unusual presentation in children, and reporting such cases may lead to early diagnosis and initiation of prompt interventions.

The Outcome of Multicystic Dysplastic Kidney Disease Patients at King Abdulaziz Medical City in Riyadh.

Background Multicystic dysplastic kidney (MCDK) is a type of kidney dysplasia consisting of many irregular, various-sized cysts divided by dysplastic renal tissue, which negatively impacts kidney function. MCDK is one of the most common renal congenital disorders seen in antenatal ultrasounds. The typical prognosis of MCDK is complete or partial involution that starts antenatally and continues postnatally. The aim of the study was to shed light on the overall outcome of patients with MCDK. Methods We retrospectively collected data on MCDK patients from 2016 until 2022 at King Abdulaziz Medical City, Ministry of National Guard Health Affairs in Saudi Arabia, Riyadh. The data included the recording of epidemiological data, radiological and laboratory reports, and the presence of urological or non-urologically associated anomalies. Results A total of 57 patients with MCDK were reviewed. Seven of them were excluded due to the diagnosis of bilateral MCDK, which was incompatible with life. Of the remaining 50 patients, the right kidney was affected in 52% of them. Most patients were diagnosed antenatally (98%). The mean duration of follow-up for the study was 48 months. Vesicoureteral reflux (VUR) was detected in 22% of the total sample. Overall, 90% of the patients underwent kidney involution. A small percentage had genitourinary anomalies (20%), while a larger percentage (48%) had extrarenal abnormalities. Conclusion Multicystic dysplastic kidney disease is relatively common in children. The prognosis is affected by the presence of genitourinary and non-genitourinary anomalies. Patients have an overall good prognosis with conservative management. Antenatal screening, diagnosis, and long-term nephrological follow-up are essential for the optimal management of patients.