1 - Pediatric Nephrology Unit, Hospital Dona Estefânia, CHLC-EPE, Lisbon, Portugal
- 51th Annual Scientific Meeting of the European Society for Paediatric Nephrology, Antalya (Turkey), 3-6/October/2018 (poster)
Abstract:
Introduction: Nephronophthisis (NPH) is an autosomal recessive disease characterized by chronic tubulointerstitial nephritis that progresses to end-stage renal disease in children and adolescents. The juvenile form manifests by urine concentration defect during the first decade of life and 20% of patients have additional extra-renal manifestations. Currently, the definitive diagnosis is made by molecular genetic approach. All NPH gene products are expressed in the primary cilia and centrosomes, therefore NPH is considered to be a ciliopathy.
Clinical Case: A nine-year-old female patient presented to hospital with a history of uncontrolled vomiting. Past history was significant for reduced visual acuity and hypotonia, moderated intellectual disability and minor cerebellar dysplasia of unknown etiology. At physical examination, signs of moderate dehydration were present. Blood analyses revealed haemoglobin 10,1 g/dL, urea 142 mg/dL creatinine 2,1 mg/dL, sodium 139 mEq/L and urinary density 1005. Acute kidney injury was suspected and hospital admission was prompt. After rehydration, renal function stabilized at high levels (urea 101 mg/dL and creatinine 1.85 mg/dL - GFR 30,14 mL/min/1.73m2) and urinary concentration defect was maintained. On detailed history, she complained of polyuria, enuresis and polydipsia several years ago. Renal ultrasound revealed bilateral echogenic kidneys with loss of corticomedullary differentiation. Based on clinical picture, a ciliopathy was considered, particularly NPH with ocular and neurological manifestation, and confirmed by array, which revealed a bialelic delection on gene NPHP1. She started conservative therapy for end stage renal disease and parents were referred for genetic counselling.
Conclusions: This case highlights the diagnostic challenge of NPH because of its unspecific clinical presentation and significant overlap with other ciliopathies. Molecular genetic studies have identified more than 20 genes. Nevertheless, there is yet little genotype-phenotype correlation, so the creation of clinical registries is of paramount importance to improve diagnostic and therapeutic management of NPH.
Keywords: Nephronophtisis, cerebellar dysplasia, tubulointerstitial nephritis