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Accurate diagnosis of primary hyperoxaluria (PH) has important therapeutic consequences. Since biochemical assessment can be unreliable, genetic testing is a crucial diagnostic tool for patients with PH to define the disease type. Patients with PH type 1 (PH1) have a worse prognosis than those with other PH types, despite the same extent of oxalate excretion. The relation between genotype and clinical phenotype in PH1 is extremely heterogeneous with respect to age of first symptoms and development of kidney failure. Some mutations are significantly linked to pyridoxine-sensitivity in PH1, such as homozygosity for p.G170R and p.F152I combined with a common polymorphism. Although patients with these mutations display on average better outcomes, they may also present with CKD stage 5 in infancy. In vitro studies suggest pyridoxine-sensitivity for some other mutations, but confirmatory clinical data are lacking (p.G47R, p.G161R, p.I56N/major allele) or scarce (p.I244T). These studies also suggest that other vitamin B6 derivatives than pyridoxine may be more effective and should be a focus for clinical testing. PH patients displaying the same mutation, even within one family, may have completely different clinical outcomes. This discordance may be caused by environmental or genetic factors that are unrelated to the effect of the causative mutation(s). No relation between genotype and clinical or biochemical phenotypes have been found so far in PH types 2 and 3. This manuscript reviews the current knowledge on the genetic background of the three types of primary hyperoxaluria and its impact on clinical management, including prenatal diagnosis., Author(s): Giorgia Mandrile [sup.1] , Bodo Beck [sup.2] , Cecile Acquaviva [sup.3] , Gill Rumsby [sup.4] , Lisa Deesker [sup.5] , Sander Garrelfs [sup.5] , Asheeta Gupta [sup.6] , Justine [...]

Background Paediatric renal biopsy standards introduced in the UK in 2010 were intended to reduce variation and improve practice. A concurrent national drive was aimed at building robust paediatric nephrology networks to ensure services cater for the needs of the family and minimise time away from home. We aimed to identify current national practice since these changes on behalf of the British Association for Paediatric Nephrology. Methods All UK paediatric nephrology centres were invited to complete a survey of their biopsy practice, including advance preparation. From 1 January to 30 June 2012, a national prospective audit of renal biopsies was undertaken at participating centres comparing practice with the British Association for Paediatric Nephrology (BAPN) standards and audit results from 2005. Results Survey results from 11 centres demonstrated increased use of pre-procedure information leaflets (63.6 % vs 45.5 %, P = 0.39) and play preparation (90.9 % vs 9.1 %, P = 0.0001). Audit of 331 biopsies showed a move towards day-case procedures (49.5 % vs 32.9 %, P = 0.17) and reduced major complications (4.5 % vs 10.4 %, P = 0.002). Biopsies with 18-gauge needles had significantly higher mean pass rates (3.2 vs 2.3, P = 0.0008) and major complications (15.3 % vs 3.3 %, P = 0.0015) compared with 16-gauge needles. Conclusions Percutaneous renal biopsy remains a safe procedure in children, thus improving family-centered service provision in the UK., Author(s): Asheeta Gupta[sup.1] , Joanna Campion-Smith[sup.2] , Wesley Hayes[sup.3] , Jane E. Deal[sup.4] , Rodney D. Gilbert[sup.5] , Carole Inward[sup.3] , Brian A. Judd[sup.6] , Rajesh G. Krishnan[sup.7] , Stephen [...]

Only two families have been reported with biallelic TMEM260 variants segregating with structural heart defects and renal anomalies syndrome (SHDRA). With a combination of genome, exome sequencing and RNA studies, we identified eight individuals from five families with biallelic TMEM260 variants. Variants included one multi‐exon deletion, four nonsense/frameshifts, two splicing changes and one missense change. Together with the published cases, analysis of clinical data revealed ventricular septal defects (12/12), mostly secondary to truncus arteriosus (10/12), elevated creatinine levels (6/12), horse‐shoe kidneys (1/12) and renal cysts (1/12) in patients. Three pregnancies were terminated on detection of severe congenital anomalies. Six patients died between the ages of 6 weeks and 5 years. Using a range of stringencies, carrier frequency for SHDRA was estimated at 0.0007–0.007 across ancestries. In conclusion, this study confirms the genetic basis of SHDRA, expands its known mutational spectrum and clarifies its clinical features. We demonstrate that SHDRA is a severe condition associated with substantial mortality in early childhood and characterised by congenital cardiac malformations with a variable renal phenotype. [ABSTRACT FROM AUTHOR]

Objective: To design and assess a visual genomic explainer focusing on plain language and engaging imagery. The explainer aimed to support doctors' comprehension of complex genomic concepts and results and act as a resource promoting the integration of genomic testing into mainstream care., Design: Prospective genomic resource development and questionnaire., Setting: Regional and tertiary hospitals in Australia and Ireland, private and community-based clinicians in Australia., Participants: Recruitment of paediatricians and nephrologists in Australia and paediatricians in Ireland was multi-faceted. Emails with survey links were circulated through training bodies, advanced trainee networks, departmental heads, and professional societies., Main Outcome Measures: Comprehension, engagement and perception of the visual explainer., Results: Most clinicians surveyed (95% (53) Australian group, 100% (29) Irish group) felt that genomics would be a useful tool in their practice. 77% of Australian paediatric respondents and 73% of Irish paediatric respondents felt that genomics was underutilised. Challenges encountered with genomic testing included poor patient comprehension of the testing process and results along with difficulties perceived by clinicians in explaining complex results. 89% of Australian paediatricians and 100% of Irish paediatricians surveyed would recommend the use of the explainer to other professionals in their field., Conclusion: This genomic resource was acceptable to clinicians and could be a useful tool to support paediatricians integrating genomic testing into mainstream care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)