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Adenosine Kinase De...
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Bjursell, Magnus K.Karolinska Institutet
(författare)
Adenosine Kinase Deficiency Disrupts the Methionine Cycle and Causes Hypermethioninemia, Encephalopathy, and Abnormal Liver Function
- Artikel/kapitelEngelska2011
Förlag, utgivningsår, omfång ...
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Elsevier BV,2011
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:kth-46846
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https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-46846URI
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https://doi.org/10.1016/j.ajhg.2011.09.004DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:123371030URI
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-161045URI
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https://gup.ub.gu.se/publication/162040URI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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QC 20111107
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Four inborn errors of metabolism (IEMs) are known to cause hypermethioninemia by directly interfering with the methionine cycle. Hypermethioninemia is occasionally discovered incidentally, but it is often disregarded as an unspecific finding, particularly if liver disease is involved. In many individuals the hypermethioninemia resolves without further deterioration, but it can also represent an early sign of a severe, progressive neurodevelopmental disorder. Further investigation of unclear hypermethioninemia is therefore important. We studied two siblings affected by severe developmental delay and liver dysfunction. Biochemical analysis revealed increased plasma levels of methionine, S-adenosylmethionine (Ado Met), and S-adenosylhomocysteine (AdoHcy) but normal or mildly elevated homocysteine (Hcy) levels, indicating a block in the methionine cycle. We excluded S-adenosylhomocysteine hydrolase (SAHH) deficiency, which causes a similar biochemical phenotype, by using genetic and biochemical techniques and hypothesized that there was a functional block in the SAHH enzyme as a result of a recessive mutation in a different gene. Using exome sequencing, we identified a homozygous c.902C>A (p.Ala301Glu) missense mutation in the adenosine kinase gene (ADK), the function of which fits perfectly with this hypothesis. Increased urinary adenosine excretion confirmed ADK deficiency in the siblings. Four additional individuals from two unrelated families with a similar presentation were identified and shown to have a homozygous c.653A>C (p.Asp218Ala) and c.38G>A (p.Gly13Glu) mutation, respectively, in the same gene. All three missense mutations were deleterious, as shown by activity measurements on recombinant enzymes. ADK deficiency is a previously undescribed, severe IEM shedding light on a functional link between the methionine cycle and adenosine metabolism.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Blom, Henk J.
(författare)
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Asin-Cayuela, Jorge
(författare)
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Engvall, Martin L.Karolinska Institutet
(författare)
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Lesko, NicoleKarolinska Institutet
(författare)
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Balasubramaniam, Shanti
(författare)
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Brandberg, Goran
(författare)
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Halldin, MariaUppsala universitet,Pediatrik(Swepub:uu)marihall
(författare)
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Falkenberg, Maria,1968Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institute of Biomedicine(Swepub:gu)xfamar
(författare)
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Jakobs, Cornelis
(författare)
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Smith, Desiree
(författare)
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Struys, Eduard
(författare)
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von Dobeln, UlrikaKarolinska Institutet
(författare)
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Gustafsson, Claes M,1966Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institute of Biomedicine(Swepub:gu)xgucla
(författare)
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Lundeberg, JoakimKTH,Science for Life Laboratory, SciLifeLab,Genteknologi(Swepub:kth)u1qkn9kw
(författare)
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Wedell, AnnaKarolinska Institutet
(författare)
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Karolinska InstitutetPediatrik
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:American Journal of Human Genetics: Elsevier BV89:4, s. 507-5150002-92971537-6605
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Bjursell, Magnus ...
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Blom, Henk J.
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Asin-Cayuela, Jo ...
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Engvall, Martin ...
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Lesko, Nicole
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Balasubramaniam, ...
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Brandberg, Goran
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Halldin, Maria
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Falkenberg, Mari ...
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Jakobs, Cornelis
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Smith, Desiree
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Struys, Eduard
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von Dobeln, Ulri ...
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Gustafsson, Clae ...
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Lundeberg, Joaki ...
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Wedell, Anna
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