Alport Syndrome in Iceland: Epidemiology and Outcomes

Abstract

Introduction: Alport syndrome (AS) is caused by mutations in the collagen IV genes, COL4A3, COL4A4 and COL4A5. Three types of AS have been described: X-linked AS (XLAS), autosomal recessive AS (ARAS) and autosomal dominant AS (ADAS). The aim of this study was to examine the epidemiology and outcomes of AS in Iceland.Methods: This was a retrospective study of all Icelandic AS cases in the period 1968-2023. Affected individuals were identified through diagnosis codes, the Icelandic Renal Registry, and family tracing. Medical records were reviewed for the confirmation of diagnosis. End-stage kidney disease (ESKD) was defined as the need for kidney replacement therapy. Clinical characteristics, family history and genetic testing were used for the diagnosis of X-linked AS. The diagnosis of autosomal AS was made in individuals with persistent haematuria in whom a secondary cause had been excluded. Results: We identified 76 individuals with AS, 52 with XLAS (13 males) and 24 individuals with autosomal AS (8 males). Diagnosis was confirmed with genetic testing in 45 of the 52 XLAS patients and in 2 autosomal AS cases. The mean (±SD) age at XLAS diagnosis was 28.5±22.3 years and 9.4±9.6 years for autosomal AS. The prevalence of AS in January 2024 was 17.7 per 100,000 population. The average yearly incidence of XLAS in the last 10 years was 0.54 individuals per 100,000 population. Five autosomal AS patients (20.8%) had some degree of proteinuria at latest follow-up, but all had normal kidney function. A total of 10 individuals with XLAS developed ESKD, 7 men and 3 women, at the median (range) age of 19 (16-25) and 60 (37-69) years for males and females, respectively. Conclusions: The prevalence of AS in Iceland is similar to other western countries. A high proportion of males whereas only a few women with XLAS progress to ESKD. The outcomes of individuals with autosomal AS are excellent.

Inngangur: Alport syndrome (AS) orsakast af stökkbreytingum í kollagen IV genum, COL4A3, COL4A4 og COL4A5. Þrjár gerðir AS hafa verið skilgreindar: kynbundið AS (XLAS) og tvær samlitnings AS; ríkjandi AS (ADAS) og víkjandi AS (ARAS). Markmið verkefnisins var að rannsaka faraldsfræði og horfur AS á Íslandi. Efni og aðferðir: Rannsóknin var afturskyggn og náði til allra Íslendinga sem greindust með AS á árunum 1968-2023. Leitað var að tilfellum með greiningarkóðum úr rafrænum sjúkraskrám, í Íslensku nýrnabilunarskránni og með ættrakningu. Greiningar voru staðfestar með lestri sjúkraskráa. Lokastigsnýrnabilun (LSNB) var skilgreind sem þörf fyrir skilun eða nýraígræðslu. Klínísk birtingarmynd, fjölskyldusaga og erfðarannsóknir voru notaðar við greiningu XLAS. Einstaklingar með viðvarandi blóðmigu þar sem aðrar orsakir höfðu verið útilokaðar voru taldir hafa samlitnings AS. Niðurstöður: Alls greindust 76 einstaklingar með AS, 52 með XLAS (13 karlkyns) og 24 með samlitnings AS (8 karlkyns). Af 52 XLAS tilfellum voru 45 staðfest með erfðagreiningu en einungis 2 samlitnings AS tilfelli. Meðalaldur (±staðalfrávik) við greiningu XLAS var 28,5±22,3 ár en 9,4±9,6 ár fyrir samlitnings AS. Algengi AS í janúar 2024 var 17,7 fyrir hverja 100.000 íbúa. Árlegt nýgengi XLAS síðustu 10 ár var að meðaltali 0,54 fyrir hverja 100.000 íbúa. Fimm einstaklingar með samlitnings AS (20,8%) voru með albúmín í þvagi við síðasta eftirlit en nýrnastarfsemi þeirra allra var eðlileg. Alls fengu 10 einstaklingar með XLAS lokastigsnýrnabilun, 7 karlar og 3 konur, miðgildi (spönn) aldurs við LSNB var 19 (16-25) ár hjá körlum og 60 (37-69) ár hjá konum.Ályktanir: Algengi Alport syndrome á Íslandi er svipað og í nágrannalöndum. Hátt hlutfall karla en fáar konur með XLAS þurfa meðferð við LSNB. Horfur einstaklinga með samlitnings AS eru góðar.