{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T22:52:34Z","timestamp":1773787954677,"version":"3.50.1"},"reference-count":15,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2008,1,17]],"date-time":"2008-01-17T00:00:00Z","timestamp":1200528000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2008,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>MELAS (mitochondrial encephalopathy with lactic acidosis and stroke\u2010like episodes) is a maternally inherited disorder characterized by recurrent cerebral infarctions that do not conform to discreet vascular territories. Here we report on a patient who presented at 7 years of age with loss of consciousness and severe metabolic acidosis following vomiting and dehydration. She developed progressive sensorineural hearing loss, myopathy, ptosis, short stature, and mild developmental delays after normal early development. Biochemical testing identified metabolites characteristic of medium\u2010chain acyl\u2010CoA dehydrogenase (MCAD) deficiency (hexanoylglycine and suberylglycine), but also severe lactic acidemia (10\u201325 mM) and, in urine, excess of lactic acid, intermediates of the citric cycle, and marked ketonuria, suggesting mitochondrial dysfunction. She progressed rapidly to develop temporary cortical blindness. Brain imaging indicated generalized atrophy, more marked on the left side, in addition to white matter alterations consistent with a mitochondrial disorder. Magnetic resonance angiography indicated occlusion of the left cerebral artery with development of collateral circulation (Moyamoya syndrome). This process worsened over time to involve the other side of the brain. A muscle biopsy indicated the presence of numerous ragged red fibers. Molecular testing confirmed compound heterozygosity for the common mutation in the MCAD gene (985A&gt;G) and a second pathogenic mutation (233T&gt;C). MtDNA testing indicated that the muscle was almost homoplasmic for the 3243A&gt;T mutation in tRNALeu, with a lower mutant load (about 50% heteroplasmy) in blood and skin fibroblasts. These results indicate that mitochondrial disorders may be associated with severe vascular disease resulting in Moyamoya syndrome. The contribution of the concomitant MCAD deficiency to the development of the phenotype in this case is unclear. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.31841","type":"journal-article","created":{"date-parts":[[2008,1,18]],"date-time":"2008-01-18T00:18:58Z","timestamp":1200615538000},"page":"361-367","source":"Crossref","is-referenced-by-count":25,"title":["Progressive cerebral vascular degeneration with mitochondrial encephalopathy"],"prefix":"10.1002","volume":"146A","author":[{"given":"Nicola","family":"Longo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iris","family":"Schrijver","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannes","family":"Vogel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynn M.","family":"Pique","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tina M.","family":"Cowan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marzia","family":"Pasquali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary K.","family":"Steinberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary L.","family":"Hedlund","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon L.","family":"Ernst","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renata C.","family":"Gallagher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory M.","family":"Enns","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,1,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1086\/320602"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2006.00731.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1071335"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000220197.36849.1e"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0733-8619(03)00015-X"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2004.04.004"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2005.01.013"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00688185"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410250611"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.6496"},{"key":"e_1_2_7_12_1","first-page":"2367","volume-title":"The metabolic and molecular bases of inherited disease","author":"Shoffner JM","year":"2001"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(03)00373-5"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2005.09.020"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5407.1482"},{"key":"e_1_2_7_16_1","first-page":"2425","volume-title":"The metabolic and molecular bases of inherited disease","author":"Wallace DC","year":"2001"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.31841","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.31841","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T06:59:44Z","timestamp":1697612384000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.31841"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,1,17]]},"references-count":15,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2008,2]]}},"alternative-id":["10.1002\/ajmg.a.31841"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.31841","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,1,17]]}}}