A common X-linked inborn error of carnitine biosynthesis may be a risk factor for nondysmorphic autism.

Proceedings of the National Academy of Sciences of the United States of America
Patricia B S Celestino-SoperArthur L Beaudet

Abstract

We recently reported a deletion of exon 2 of the trimethyllysine hydroxylase epsilon (TMLHE) gene in a proband with autism. TMLHE maps to the X chromosome and encodes the first enzyme in carnitine biosynthesis, 6-N-trimethyllysine dioxygenase. Deletion of exon 2 of TMLHE causes enzyme deficiency, resulting in increased substrate concentration (6-N-trimethyllysine) and decreased product levels (3-hydroxy-6-N-trimethyllysine and γ-butyrobetaine) in plasma and urine. TMLHE deficiency is common in control males (24 in 8,787 or 1 in 366) and was not significantly increased in frequency in probands from simplex autism families (9 in 2,904 or 1 in 323). However, it was 2.82-fold more frequent in probands from male-male multiplex autism families compared with controls (7 in 909 or 1 in 130; P = 0.023). Additionally, six of seven autistic male siblings of probands in male-male multiplex families had the deletion, suggesting that TMLHE deficiency is a risk factor for autism (metaanalysis Z-score = 2.90 and P = 0.0037), although with low penetrance (2-4%). These data suggest that dysregulation of carnitine metabolism may be important in nondysmorphic autism; that abnormalities of carnitine intake, loss, transport, or synthesis may be impo...Continue Reading

References

Jan 1, 1990·Biology of the Neonate·E Schmidt-Sommerfeld, D Penn
Jan 1, 1995·Genetic Epidemiology·R E McGinnisR S Spielman
Apr 30, 1998·Journal of the Neurological Sciences·J C RubioJ Arenas
Aug 26, 1998·Medical Hypotheses·J Lombard
Jan 23, 2002·The Biochemical Journal·Frédéric M Vaz, Ronald J A Wanders
Sep 6, 2002·Autism : the International Journal of Research and Practice·Fiona J ScottCarol Brayne
Feb 1, 2005·Journal of Autism and Developmental Disorders·Pauline A FilipekJ Jay Gargus
Apr 7, 2005·Indian Journal of Pediatrics·Veena KalraSavita Sapra
Dec 29, 2005·Nature Genetics
Feb 10, 2006·Nature Genetics·Steven A McCarrollUNKNOWN International HapMap Consortium
Apr 8, 2006·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Nicola LongoMarzia Pasquali
Mar 17, 2007·Science·Jonathan SebatMichael Wigler
Dec 28, 2007·Journal of Child Neurology·Virginia C N Wong, Stella L H Hui
Feb 7, 2008·American Journal of Human Genetics·Christian R MarshallStephen W Scherer
Apr 3, 2008·American Journal of Medical Genetics. Part a·Judith H MilesJanet E Farmer
Apr 17, 2008·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Zhishuo OuA Craig Chinault
Oct 23, 2008·The Annals of Pharmacotherapy·Jeffery D EvansEmily W Evans
Aug 15, 2009·American Journal of Physiology. Gastrointestinal and Liver Physiology·Masaharu FujitaIkumi Tamai
Feb 16, 2010·Nature Genetics·Santhosh GirirajanEvan E Eichler
Mar 23, 2010·IUBMB Life·Karin StrijbisBen Distel
Apr 20, 2010·Nutrition & Metabolism·Judith L FlanaganQian Garrett
Aug 26, 2010·Current Opinion in Critical Care·Satyam Sarma, Mihai Gheorghiade
May 12, 2011·The American Journal of Psychiatry·Young Shin KimRoy Richard Grinker
Jun 2, 2011·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·David A GeierMark R Geier
Jun 11, 2011·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Philip M BooneJames R Lupski
Mar 1, 2005·Indian Journal of Pediatrics·Veena KalraSavita Sapra

❮ Previous
Next ❯

Citations

Jul 17, 2013·Proceedings of the National Academy of Sciences of the United States of America·Arthur Beaudet
Oct 23, 2012·Science·Arthur L Beaudet
Jul 24, 2013·Annual Review of Genomics and Human Genetics·Guillaume HuguetThomas Bourgeron
Mar 15, 2014·PLoS Computational Biology·Andrey RzhetskyRobert D Gibbons
Jan 24, 2014·PloS One·Luigi ServilloMaria Luisa Balestrieri
Jan 15, 2014·Global Advances in Health and Medicine : Improving Healthcare Outcomes Worldwide·Derrick Macfabe
Jan 15, 2014·Global Advances in Health and Medicine : Improving Healthcare Outcomes Worldwide·Pamela J Compart
Nov 2, 2013·Trends in Genetics : TIG·Luciana Musante, H Hilger Ropers
Jun 17, 2014·Bioinformatics·A Ercument CicekGultekin Ozsoyoglu
Jan 15, 2015·Annual Review of Medicine·William M Brandler, Jonathan Sebat
Feb 24, 2016·Drug Development Research·Walter H MoosKosta Steliou
Mar 8, 2016·Neuroscience and Biobehavioral Reviews·Alan Packer
Dec 17, 2015·Clinical and Translational Medicine·Sunghee OhJohn Hutton
Nov 13, 2013·Developmental Neurobiology·Salvatore Carbonetto
May 7, 2015·American Journal of Medical Genetics. Part a·Mark N ZiatsChristian P Schaaf
Sep 20, 2015·Molecular Genetics and Metabolism·Ayman W El-Hattab, Fernando Scaglia
Jan 29, 2013·Neuron·Timothy W YuChristopher A Walsh
Jan 22, 2013·Neurobiology of Disease·Guomei TangDavid Sulzer
Jul 16, 2014·Frontiers in Pediatrics·Richard Eugene Frye, Daniel A Rossignol
Jul 30, 2014·Frontiers in Pediatrics·Eleonora NapoliCecilia Giulivi
Feb 2, 2016·Biochimica Et Biophysica Acta·Nicola LongoMarzia Pasquali
Jul 14, 2017·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Arthur L Beaudet
Nov 7, 2017·Human Molecular Genetics·Eliana D WeiszThomas A Jongens
Mar 23, 2019·The Biochemical Journal·Yali WangJasmin Mecinović
Apr 25, 2019·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Mark A CanfieldJohn F Villanacci
Nov 9, 2019·The Journal of Biological Chemistry·Vytas A Bankaitis, Zhigang Xie
Dec 22, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Barbara Juraszek, Katarzyna A Nałęcz
Nov 7, 2019·Molecular Diagnosis & Therapy·Afaf El-AnsaryGeir Bjørklund
Jul 14, 2020·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Peter H LangloisJohn F Villanacci
Jul 14, 2017·Molecular Autism·Jamie ReillySanbing Shen

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autism

Autism spectrum disorder is associated with challenges with social skills, repetitive behaviors, and often accompanied by sensory sensitivities and medical issues. Here is the latest research on autism.