How to solve a clinical conundrum: Have you tried a trio exome analysis?

The following report describes the clinical journey of a 5-month-old male infant who presented with a significant kidney injury following a diarrhoeal illness. His course was complicated by severe hypertension and a number of acute life-threatening events necessitating periods of time on the intensive care unit, where he received ventilatory support and underwent renal replacement therapy and treatment with a monoclonal antibody therapy.We take the reader on a stepwise journey from presentation through to final diagnosis, discussing important biochemical, haematological and radiological features where learning points are discussed. Guidance on the use of genomic testing strategies for the non-geneticist is provided in some detail with a particular focus on the trio exome analysis that identified the diagnosis for this young boy.This complex case not only provides a number of excellent learning opportunities but also highlights the importance of early involvement of the clinical genetics team and the relevance of the trio exome analysis for rapid identification of rare monogenic diseases.

Fifteen-minute consultation: An approach to the child with nephrocalcinosis.

Nephrocalcinosis is a common problem faced in both paediatrics and neonates, which may need referral on to paediatric nephrology. This 15 min consultation aims to look at children of different age groups (neonates, children 1-5 years old and older children) looking particularly at history, examination, causes, initial investigations and management.

A targeted gene panel illuminates pathogenesis in young people with unexplained kidney failure.

BACKGROUND: Kidney failure in young people is often unexplained and a significant proportion will have an underlying genetic diagnosis. National Health Service England pioneered a comprehensive genomic testing service for such circumstances accessible to clinicians working outside of genetics. This is the first review of patients using this novel service since October 2021, following its introduction into clinical practice. METHODS: The 'Unexplained Young-Onset End-Stage Renal Disease' (test-code R257) gene panel uses targeted next generation sequencing to analyse 175 genes associated with renal disease in patients under 36 years of age. All tests undertaken between October 2021 and February 2022 were reviewed. Phenotypic data were extracted from request forms and referring clinicians contacted where additional details were required. RESULTS: Seventy-one patients underwent R257 testing over the study period. Among them, 23/71 patients (32%) were confirmed to have a genetic diagnosis and 2/71 (3%) had a genetically suggestive variant. Nephronophthisis and Alport syndrome were the most common conditions identified, (4/23 (17%) with pathogenic variants in NPHP1 and 4/23 (17%) with pathogenic variants in COL4A3/COL4A4). Positive predictors of a genetic diagnosis included a family history of renal disease (60% of positive cases) and extra-renal disease manifestations (48% of positive cases). CONCLUSION: This is the first study to evaluate the R257 gene panel in unexplained young-onset kidney failure, freely accessible to patients meeting testing criteria in England. A genetic diagnosis was identified in 32% of patients. This study highlights the essential and expanding role that genomic testing has for children and families affected by renal disease today.

Iron treatment and inflammatory bowel disease: what happens in real practice?

BACKGROUND AND AIMS: Iron deficiency anaemia (IDA), the most common extra-intestinal complication of inflammatory bowel disease (IBD), negatively impacts quality of life. We audited the recent practice of anaemia treatment in an unselected IBD population. METHODS: A questionnaire was distributed to adult IBD outpatients in a university hospital to assess the form and frequency of iron prescribed, duration of use, side effects, and completion of therapy. The efficacy of treatment was determined by the resolution of anaemia and change in haemoglobin from baseline. RESULTS: Of 87 IBD patients (60 patients with Crohn's disease, 25 with ulcerative colitis, 2 with microscopic colitis), 85 received various dosing regimens of iron tablets; 15 patients also received IV iron. Side effects were reported in 43 (51%) patients, with no clear relationship to dose prescribed and 26 (32%) patients were unable to complete the intended course. Only 36 (42%) patients completed the course of oral iron without side effects and in these patients, haemoglobin normalised in about 30%. Their median haemoglobin change was 12.5 (5.3-23.5)g/l. The median duration of treatment in those without side effects was 4.5months, and in those with adverse effects was 2months. Only one adverse effect was reported for IV iron. CONCLUSIONS: Treatment with oral iron results in failure to control anaemia in 2 out of 3 IBD patients, which is likely in part to be due to the side effects reported by over half of patients. Patients failing to tolerate or adequately respond to therapy should be offered alternative treatment.