{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T18:21:30Z","timestamp":1792520490267,"version":"4.5.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,13]],"date-time":"2022-05-13T00:00:00Z","timestamp":1652400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>\n                    3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMG-CoA lyase) is a rare inborn error of leucine degradation and ketone body synthesis, caused by homozygous or compound heterozygous disease-causing variants in\n                    <jats:italic>HMGCL<\/jats:italic>\n                    . To understand the natural history of this disease, we reviewed the biochemical, clinical, and molecular data of 62 patients from 54 different families with confirmed HMG-CoA lyase deficiency (HMGCLD) diagnosis from Saudi Arabia. The majority of the affected individuals were symptomatic. At initial diagnosis, 38 patients (61.29%) presented with hypoglycemia and 49 patients (79.03%) developed metabolic acidosis. In 27 patients (43.54%), the disorder manifested in the neonatal period, mostly within the first days of life, while 35 (56.45%) patients were diagnosed within the first year of life or beyond. All the patients were alive and developed long-term neurological complications during data collection, which may significantly influence their quality of life. Common neurological findings include seizures 17\/62 (27.41%), hypotonic 3\/62 (4.83%), speech delay 7\/62 (11.29%), hyperactivity 4\/62 (4.83%), developmental delay 6\/62 (9.677%), learning disability 15\/62 (24.14%), and ataxic gate 1\/62 (1.612%). An MRI of the brain exhibited nonspecific periventricular and deep white matter hyperintense signal changes in 16 patients (25.80%) and cerebral atrophy was found in one (1\/62; 1.612%) patient. We identified a founder variant [c.122G&amp;gt;A; p.(Arg41Gln)] in 48 affected individuals (77.41%) in the\n                    <jats:italic>HMGCL<\/jats:italic>\n                    gene. This is the largest cohort of HMGCLD patients reported from Saudi Arabia, signifying this disorder as a likely life-threatening disease, with a high prevalence in the region. Our findings suggest that diagnosis at an early stage with careful dietary management may avoid metabolic crises.\n                  <\/jats:p>","DOI":"10.3389\/fgene.2022.880464","type":"journal-article","created":{"date-parts":[[2022,5,13]],"date-time":"2022-05-13T03:42:24Z","timestamp":1652413344000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["HMG-CoA Lyase Deficiency: A Retrospective Study of 62 Saudi Patients"],"prefix":"10.3389","volume":"13","author":[{"given":"Majid","family":"Alfadhel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basma","family":"Abadel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hind","family":"Almaghthawi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Umair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuhair","family":"Rahbeeni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eissa","family":"Faqeih","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Almannai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Alasmari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Saleh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wafaa","family":"Eyaid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Alfares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuad","family":"Al Mutairi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1186\/1471-2350-7-86","article-title":"Mutations Underlying 3-Hydroxy-3-Methylglutaryl CoA Lyase Deficiency in the Saudi Population","volume":"7","author":"Al-Sayed","year":"2006","journal-title":"BMC Med. 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