{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T02:16:05Z","timestamp":1789179365588,"version":"build-2803163510"},"reference-count":9,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2010,6,25]],"date-time":"2010-06-25T00:00:00Z","timestamp":1277424000000},"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":[[2010,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Amish microcephaly (MCPHA, OMIM #607196) is a metabolic disorder that has been previously characterized by severe infantile lethal congenital microcephaly and alpha\u2010ketoglutaric aciduria. All reported patients have been from the Pennsylvania Amish community and homozygous for a p.Gly177Ala mutation in <jats:italic>SLC25A19<\/jats:italic>. We present a further male patient with MCPHA born to distantly consanguineous parents in Ontario, Canada with Amish ancestors. Microcephaly was evident at 21 weeks gestation on ultrasound. At birth, the facial appearance and brain MRI scan were characteristic of MCPHA, with the additional features of partial agenesis of the corpus callosum and a closed spinal dysraphic state. Urine levels of alpha\u2010ketoglutaric acid were normal at birth and during metabolic crisis, but were markedly elevated during a time of metabolic stability. A severe lactic acidosis was present during metabolic crises and responded to treatment with a high fat diet. At age 7 years, the child is healthy but has severe microcephaly and profound developmental delay. SLC25A19 has been described as a mitochondria inner membrane transporter for both deoxynucleotides and thiamine pyrophosphate (TPP). The biochemical phenotype of MCPHA may be attributable to decreased activity of the three mitochondrial enzymes that require TPP as a cofactor: pyruvate dehydrogenase, alpha\u2010ketoglutarate dehydrogenase, and branched chain amino acid dehydrogenase. We confirm that alpha\u2010ketoglutaric aciduria is not a constant finding in MCPHA and suggest that a persistent lactic acidemia may be more common. The diagnosis should be considered in patients with severe congenital microcephaly, especially in association with lissencephaly, dysgenesis of the corpus callosum, or a spinal dysraphic state. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.33373","type":"journal-article","created":{"date-parts":[[2010,6,26]],"date-time":"2010-06-26T06:53:40Z","timestamp":1277535220000},"page":"1747-1751","source":"Crossref","is-referenced-by-count":41,"title":["Amish microcephaly: Long\u2010term survival and biochemical characterization"],"prefix":"10.1002","volume":"152A","author":[{"given":"Victoria Mok","family":"Siu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Ratko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asuri N.","family":"Prasad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chitra","family":"Prasad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Anthony","family":"Rupar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,6,25]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-005-7051-6"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10580"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.031430998"},{"key":"e_1_2_5_5_1","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1542\/peds.58.5.713","article-title":"Ketonic diet in the management of pyruvate dehydrogenase deficiency","volume":"58","author":"Falk RE","year":"1976","journal-title":"Pediatrics"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10529"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0607661103"},{"key":"e_1_2_5_8_1","first-page":"318","volume-title":"A History of the Amish","author":"Nolt SM","year":"1992"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng948"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21752"}],"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.33373","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.33373","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,7]],"date-time":"2023-10-07T12:55:33Z","timestamp":1696683333000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.33373"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,6,25]]},"references-count":9,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2010,7]]}},"alternative-id":["10.1002\/ajmg.a.33373"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.33373","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,6,25]]}}}