{"id":5979,"date":"2026-10-19T09:48:17","date_gmt":"2026-10-19T09:48:17","guid":{"rendered":"https:\/\/phd.hi.is\/doktorsvorn\/doktorsvorn-i-laeknavisindum-hrafnhildur-linnet-runolfsdottir\/"},"modified":"2026-10-19T09:48:17","modified_gmt":"2026-10-19T09:48:17","slug":"doktorsvorn-i-laeknavisindum-hrafnhildur-linnet-runolfsdottir","status":"publish","type":"phd_defence","link":"https:\/\/phd.hi.is\/en\/doktorsvorn\/doktorsvorn-i-laeknavisindum-hrafnhildur-linnet-runolfsdottir\/","title":{"rendered":"Doktorsv\u00f6rn \u00ed l\u00e6knav\u00edsindum – Hrafnhildur Linnet Run\u00f3lfsd\u00f3ttir"},"content":{"rendered":"
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F\u00f6studaginn 21. \u00e1g\u00fast ver Hrafnhildur Linnet Run\u00f3lfsd\u00f3ttir doktorsritger\u00f0 s\u00edna \u00ed l\u00e6knav\u00edsindum vi\u00f0 L\u00e6knadeild H\u00e1sk\u00f3la \u00cdslands. Ritger\u00f0in ber heiti\u00f0 Aden\u00ednfosf\u00f3r\u00edb\u00f3s\u00fdltransferasa-skortur: Algengi og afdrif sj\u00faklinga (Adenine Phosphoribosyltransferase Deficiency: Prevalence and Clinical Outcomes).<\/p>\n

V\u00f6rninni ver\u00f0ur streymt: https:\/\/livestream.com\/hi\/doktorsvornhrafnhildur<\/a><\/p>\n

Andm\u00e6lendur eru dr. Robert Unwin, pr\u00f3fessor vi\u00f0 University College, London, og dr. Hans T\u00f3mas Bj\u00f6rnsson, pr\u00f3fessor vi\u00f0 L\u00e6knadeild H\u00e1sk\u00f3la \u00cdslands.<\/p>\n

Umsj\u00f3narkennari Hrafnhildar var Vi\u00f0ar \u00d6rn E\u00f0var\u00f0sson pr\u00f3fessor og lei\u00f0beinandi var \u00d3lafur Sk\u00fali Indri\u00f0ason, s\u00e9rfr\u00e6\u00f0il\u00e6knir vi\u00f0 Landsp\u00edtala. Auk \u00feeirra s\u00e1tu \u00ed doktorsnefnd Patrick Sulem, l\u00e6knir og yfirma\u00f0ur kl\u00edn\u00edskrar mannerf\u00f0afr\u00e6\u00f0i hj\u00e1 \u00cdslenskri erf\u00f0agreiningu, og Dawn S. Milliner, pr\u00f3fessor vi\u00f0 Mayo Clinic College of Medicine, Rochester, Minnesota \u00ed Bandar\u00edkjunum.<\/p>\n

Ingibj\u00f6rg Har\u00f0ard\u00f3ttir, pr\u00f3fessor og varadeildarforseti L\u00e6knadeildar, stj\u00f3rnar ath\u00f6fninni sem fer fram \u00ed H\u00e1t\u00ed\u00f0asal H\u00e1sk\u00f3la \u00cdslands og hefst kl. 13.00.<\/p>\n

\u00c1grip af ranns\u00f3kn<\/strong><\/p>\n

Aden\u00ednfosf\u00f3r\u00edb\u00f3s\u00fdltransferasa (APRT)-skortur er sjaldg\u00e6fur v\u00edkjandi erf\u00f0asj\u00fakd\u00f3mur sem hefur \u00ed f\u00f6r me\u00f0 s\u00e9r myndun mikils magns af 2,8-d\u00edh\u00fddrox\u00fdaden\u00edni (DHA) sem fellur \u00fat \u00ed n\u00fdrum og veldur \u00fevagf\u00e6rasteinum og kristallan\u00fdrnameini er leitt getur til n\u00fdrnabilunar. Lyfjame\u00f0fer\u00f0 me\u00f0 ox\u00edd\u00f3red\u00faktasa (XOR)-hemlunum all\u00f3p\u00farin\u00f3li og feb\u00fax\u00f3stati dregur \u00far DHA-myndun og mildar aflei\u00f0ingar sj\u00fakd\u00f3msins.<\/p>\n

Markmi\u00f0 ranns\u00f3knarverkefnisins voru a\u00f0 kanna algengi APRT-skorts, framr\u00e1s n\u00fdrnasj\u00fakd\u00f3msins, \u00e1hrif lyfjame\u00f0fer\u00f0ar og endurkomu kristallan\u00fdrnameins eftir \u00edgr\u00e6\u00f0slu n\u00fdra. Enn fremur a\u00f0 rannsaka gagnsemi n\u00fdrrar a\u00f0fer\u00f0ar til a\u00f0 m\u00e6la DHA \u00ed \u00fevagi sem byggir \u00e1 h\u00e1hra\u00f0av\u00f6kvaskilju tengdri tv\u00f6f\u00f6ldum massagreini.<\/p>\n

Alls fundust 438 tilfelli APRT-skorts \u00e1samt 62 meinvaldandi st\u00f6kkbreytingum \u00ed APRT-geninu \u00e1 heimsv\u00edsu. Sj\u00fakd\u00f3murinn er \u00f3venjulega algengur \u00e1 \u00cdslandi \u00fev\u00ed greinst hafa 35 einstaklingar og hafa allir veri\u00f0 arfhreinir fyrir s\u00f6mu st\u00f6kkbreytingu. St\u00f6kkbreytingar \u00ed APRT-geninu eru mj\u00f6g f\u00e1t\u00ed\u00f0ar \u00ed opinberum arfger\u00f0ars\u00f6fnum en t\u00ed\u00f0ni \u00feeirra bendir \u00fe\u00f3 til a\u00f0 sj\u00fakd\u00f3murinn s\u00e9 v\u00ed\u00f0a algengari en fj\u00f6ldi greindra tilfella gefur til kynna. Vi\u00f0 greiningu voru 55% sj\u00faklinga me\u00f0 n\u00fdrnasteina og 38% \u00e1gengan langvinnan n\u00fdrnasj\u00fakd\u00f3m sem leiddi til lokastigsn\u00fdrnabilunar hj\u00e1 t\u00e6pum helmingi \u00feeirra. T\u00f6f \u00e1 greiningu var algeng. Enginn af \u00feeim sem h\u00f3f me\u00f0fer\u00f0 me\u00f0 XOR-hemli \u00e1 barnsaldri f\u00e9kk alvarlegan n\u00fdrnasj\u00fakd\u00f3m. Me\u00f0al 17 sj\u00faklinga sem gengust undir \u00edgr\u00e6\u00f0slu n\u00fdra var lifun og starfsemi n\u00fdragr\u00e6\u00f0linga mun betri \u00feegar me\u00f0fer\u00f0 me\u00f0 XOR-hemli var hafin fyrir \u00edgr\u00e6\u00f0slu samanbori\u00f0 vi\u00f0 s\u00ed\u00f0ar. Sj\u00f6 n\u00fdragr\u00e6\u00f0lingar t\u00f6pu\u00f0ust vegna endurkomu DHA-kristallan\u00fdrnameins. DHA-\u00fatskilna\u00f0ur \u00ed \u00fevagi reyndist mikill en breytilegur hj\u00e1 sj\u00faklingum me\u00f0 APRT-skort en ekkert DHA greindist \u00ed \u00fevags\u00fdnum fr\u00e1 arfblendnum og heilbrig\u00f0um einstaklingum. Me\u00f0fer\u00f0 me\u00f0 all\u00f3p\u00far\u00edn\u00f3li og feb\u00fax\u00f3stati dr\u00f3 markt\u00e6kt \u00far DHA-\u00fatskilna\u00f0i.<\/p>\n

Ranns\u00f3knirnar sem \u00feessi ritger\u00f0 er bygg\u00f0 \u00e1 s\u00fdna a\u00f0 APRT-skortur er sjaldg\u00e6fur kvilli sem lei\u00f0ir yfirleitt til lokastigsn\u00fdrnabilunar ef mikil t\u00f6f ver\u00f0ur \u00e1 greiningu og me\u00f0fer\u00f0. Snemmb\u00e6r me\u00f0fer\u00f0 me\u00f0 XOR-hemli h\u00e6gir \u00e1 framr\u00e1s n\u00fdrnasj\u00fakd\u00f3msins og kemur\u00a0 \u00ed veg fyrir n\u00fdrnabilun. M\u00e6ling DHA \u00ed \u00fevagi me\u00f0 hinni n\u00fdju a\u00f0fer\u00f0 vir\u00f0ist \u00e1kj\u00f3sanleg til greiningar \u00e1 APRT-skorti, auk \u00feess a\u00f0 vera gagnleg til mats \u00e1 virkni lyfjame\u00f0fer\u00f0ar.<\/p>\n

English abstract<\/strong><\/p>\n

Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder that results in the generation and renal excretion of large amounts of 2,8-dihydroxyadenine (DHA), causing kidney stones and crystal nephropathy which can progress to end-stage kidney disease (ESKD). Treatment with the xanthine oxidoreductase (XOR) inhibitors allopurinol and febuxostat reduces DHA generation and attenuates renal manifestations.<\/p>\n

The aims of this thesis included assessment of the prevalence of APRT deficiency and examination of long-term renal outcomes and the effects of treatment.<\/p>\n

A total of 438 cases of APRT deficiency were identified worldwide, together with 62 pathogenic mutations in the APRT gene. Nephrolithiasis was the most common clinical manifestation at diagnosis, followed by advanced chronic kidney disease (CKD). None of the patients who initiated XOR inhibitor treatment in childhood experienced progressive CKD. Patients receiving XOR inhibitor treatment prior to kidney transplantation had better outcomes than those who did not. Urinary DHA excretion, measured using a novel UPLC-MS\/MS assay, was high but variable in patients with APRT deficiency, whereas DHA was not detected in urine samples from heterozygotes and healthy individuals. Treatment with allopurinol and febuxostat significantly reduced DHA excretion.<\/p>\n

The studies presented in this thesis demonstrate that APRT deficiency is a rare disease that results in ESKD in the absence of timely diagnosis and treatment. Early initiation of XOR inhibitor therapy prevents adverse renal outcomes. The novel urinary DHA assay appears very accurate in the diagnosis of APRT deficiency.<\/p>\n

Um doktorsefni\u00f0<\/strong><\/p>\n

Hrafnhildur Linnet Run\u00f3lfsd\u00f3ttir f\u00e6ddist \u00ed Reykjav\u00edk \u00e1ri\u00f0 1985. H\u00fan lauk st\u00fadentspr\u00f3fi af n\u00e1tt\u00farufr\u00e6\u00f0ibraut Menntask\u00f3lans \u00ed Reykjav\u00edk 2005. Hrafnhildur h\u00f3f n\u00e1m \u00ed l\u00e6knisfr\u00e6\u00f0i vi\u00f0 L\u00e6knadeild H\u00e1sk\u00f3la \u00cdslands hausti\u00f0 2010, lauk bakkal\u00e1rgr\u00e1\u00f0u 2013 og emb\u00e6ttispr\u00f3fi vori\u00f0 2016 vi\u00f0 sama sk\u00f3la. A\u00f0 loknu kand\u00eddats\u00e1ri h\u00f3f h\u00fan s\u00e9rn\u00e1m \u00ed almennum lyfl\u00e6kningum \u00e1 Landsp\u00edtala sem h\u00fan stundar enn. Foreldrar Hrafnhildar eru Ragnhei\u00f0ur Linnet og Run\u00f3lfur P\u00e1lsson. Hrafnhildur er gift Birni R\u00fanari Egilssyni og eiga \u00feau tv\u00f6 b\u00f6rn, Au\u00f0i Katr\u00ednu og Run\u00f3lf Egil.<\/p>\n<\/div><\/div>","protected":false},"featured_media":1163,"template":"","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"_phd_date_start":"2020-08-21T13:00:00+00:00","_phd_date_end":"2020-08-21T16:00:00+00:00","_phd_location":"A\u00f0albygging H\u00e1t\u00ed\u00f0asalur","_phd_admission":"A\u00f0gangur \u00f3keypis","_phd_thesis_title":"Aden\u00ednfosf\u00f3r\u00edb\u00f3s\u00fdltransferasa-skortur: Algengi og afdrif sj\u00faklinga (Adenine Phosphoribosyltransferase Deficiency: Prevalence and Clinical Outcomes)","_phd_source_url":"https:\/\/gamli.hi.is\/vidburdir\/doktorsvorn_i_laeknavisindum_hrafnhildur_linnet_runolfsdottir","_phd_source_node_id":"345531","_phd_source_type":"vidburdir","_phd_member_id":161,"footnotes":""},"phd_school":[60,67],"phd_discipline":[69],"class_list":["post-5979","phd_defence","type-phd_defence","status-publish","has-post-thumbnail","hentry","phd_school-heilbrigdisvisindasvid","phd_school-laeknadeild","phd_discipline-phd-i-laeknavisindum"],"_links":{"self":[{"href":"https:\/\/phd.hi.is\/en\/wp-json\/wp\/v2\/phd_defence\/5979","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/phd.hi.is\/en\/wp-json\/wp\/v2\/phd_defence"}],"about":[{"href":"https:\/\/phd.hi.is\/en\/wp-json\/wp\/v2\/types\/phd_defence"}],"version-history":[{"count":0,"href":"https:\/\/phd.hi.is\/en\/wp-json\/wp\/v2\/phd_defence\/5979\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/phd.hi.is\/en\/wp-json\/wp\/v2\/media\/1163"}],"wp:attachment":[{"href":"https:\/\/phd.hi.is\/en\/wp-json\/wp\/v2\/media?parent=5979"}],"wp:term":[{"taxonomy":"phd_school","embeddable":true,"href":"https:\/\/phd.hi.is\/en\/wp-json\/wp\/v2\/phd_school?post=5979"},{"taxonomy":"phd_discipline","embeddable":true,"href":"https:\/\/phd.hi.is\/en\/wp-json\/wp\/v2\/phd_discipline?post=5979"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}