title: From juvenile hyperuricaemia to dysfunctional uromodulin: an ongoing metamorphosis.
abstract: Familial juvenile hyperuricaemic nephropathy (FJHN) is a diagnosis that is easily missed. It has taken a long time to clarify the pathophysiology and prevalence of this disease entity which has been shown to be genetically identical to medullary cystic kidney disease (MCKD) type II. The initial suspicion that uric acid was the noxious agent has been replaced by the recognition that a mutant uromodulin (UMOD) is the real culprit-although the exact mechanisms of pathogenicity remain uncertain. The mutation has been traced to the UMOD gene in chromosome 16. The disease is characterised by the classic triad of autosomal dominant inheritance, progressive renal failure beginning in the third to fifth decade of life and gout. Phenotypically similar but genotypically distinct entities have been described over the last 10 years, making a clinical diagnosis difficult. These include mutations in the renin, hepatocyte nuclear factor 1-β and mucin 1 genes. UMOD-associated kidney disease has been proposed as a logical diagnostic label to replace FJHN, but given all these other mutations, an over-arching diagnostic term of 'autosomal dominant tubulointerstitial kidney disease' (ADTKD) has been recently adopted. Allopurinol has been suggested as a therapeutic agent, but unfortunately this was based on non-randomised uncontrolled trials with small patient numbers.
authors.affiliation: Wessex Kidney Centre & University of Southampton, Queen Alexandra Hospital, Portsmouth, PO6 3LY, UK. gvr@porthosp.nhs.uk.
authors.forename: Gopalakrishnan
authors.initials: G
authors.lastname: Venkat-Raman
authors.affiliation: Wessex Kidney Centre & University of Southampton, Queen Alexandra Hospital, Portsmouth, PO6 3LY, UK.
authors.forename: Christine
authors.initials: C
authors.lastname: Gast
authors.affiliation: Purine Research Laboratory, St Thomas' Hospital, London, UK.
authors.forename: Anthony
authors.initials: A
authors.lastname: Marinaki
authors.affiliation: Purine Research Laboratory, St Thomas' Hospital, London, UK.
authors.forename: Lynnette
authors.initials: L
authors.lastname: Fairbanks
mesh_terms: D000293:Adolescent; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D006073:Gout / Q000150:complications / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics; D006801:Humans; D033461:Hyperuricemia / Q000150:complications / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy; D007674:Kidney Diseases / Q000150:complications / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy; D018396:Mucin-1 / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D016891:Polycystic Kidney, Autosomal Dominant / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D015995:Prevalence; D051437:Renal Insufficiency / Q000209:etiology* / Q000235:genetics; D012083:Renin / Q000235:genetics; D014527:Uric Acid / Q000378:metabolism; D058949:Uromodulin / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
chemical_list: C496495:HNF1B protein, human; C060192:MUC1 protein, human; D018396:Mucin-1; C548612:UMOD protein, human; D058949:Uromodulin; D051539:Hepatocyte Nuclear Factor 1-beta; D014527:Uric Acid; D012083:Renin
keywords: Autosomal dominant tubulointerstitial kidney disease; Familial juvenile hyperuricaemic nephropathy; Gout; HNF1-β; Mucin-1; Renin; Uromodulin