{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T09:06:53Z","timestamp":1778576813845,"version":"3.51.4"},"reference-count":28,"publisher":"Wiley","issue":"S3","license":[{"start":{"date-parts":[[2007,12,17]],"date-time":"2007-12-17T00:00:00Z","timestamp":1197849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004263","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Rio Grande do Sul","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004263","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007380","name":"Funda\u00e7\u00e3o Instituto de Pesquisas Econ\u00f4micas","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007380","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2008,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>3\u2010Hydroxy\u20103\u2010methylglutaryl\u2010CoA lyase (HL) deficiency (3\u2010hydroxy\u20103\u2010methylglutaric aciduria, 3\u2010HMG) is a rare autosomal recessive inborn error of metabolism involving the final step of leucine degradation. HL is the key enzyme for the production of glucose\u2010sparing ketone bodies for brain. Positive biochemical findings are metabolic acidosis, hyperammonaemia, and hypoketotic hypoglycaemia in the neonatal period or infancy. In the present study we report 15 Brazilian patients with HL deficiency and present their clinical and biochemical findings. Urine from all patients contained large amounts of 3\u2010hydroxy\u20103\u2010methylglutaric, 3\u2010methylglutaconic, 3\u2010hydroxyisovaleric and 3\u2010methylglutaric acids, and 3\u2010methylcrotonylglycine was also observed in 13 patients. The main features at clinical presentation were hypoglycaemia (12 patients), seizures (10 patients), metabolic acidosis (9 patients), vomiting (6 patients), and hepatomegaly (5 patients). All but two patients were of Portuguese ancestry. HL deficiency comprised 7.3% of total organic acidurias detected in our laboratory during a 13\u2010year time span, indicating a high incidence of this disorder in Brazil. Limited molecular characterization (4\/15 patients only) revealed two mutations common for individuals of Portuguese\/Spanish (Iberian Peninsula) ancestry (E37X and V168fs(\u22122)). Our findings increase the number of HL\u2010deficient patients and reinforce the characteristic phenotypic picture of the disease. Effective dietary interventions based on mild protein restriction and avoidance of fasting and possibly alternative C<jats:sub>5<\/jats:sub> ketone body generating therapy for this disorder may provide further impetus and rationale for expanded newborn screening of HL deficiency.<\/jats:p>","DOI":"10.1007\/s10545-007-0756-y","type":"journal-article","created":{"date-parts":[[2007,12,14]],"date-time":"2007-12-14T13:37:15Z","timestamp":1197639435000},"page":"511-515","source":"Crossref","is-referenced-by-count":15,"title":["Incidence of 3\u2010hydroxy\u20103\u2010methylglutaryl\u2010coenzyme A lyase (HL) deficiency in Brazil, South America"],"prefix":"10.1002","volume":"31","author":[{"given":"C. R.","family":"Vargas","sequence":"first","affiliation":[{"name":"Medical Genetics Service HCPA Porto Alegre RS Brazil"},{"name":"Department of Analysis PPGCF, UFRGS Porto Alegre RS Brazil"},{"name":"Deparment of Biochemistry ICBS, UFRGS Porto Alegre Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Sitta","sequence":"additional","affiliation":[{"name":"Medical Genetics Service HCPA Porto Alegre RS Brazil"},{"name":"Deparment of Biochemistry ICBS, UFRGS Porto Alegre Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Medical Genetics Service HCPA Porto Alegre RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. C.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Deparment of Biochemistry ICBS, UFRGS Porto Alegre Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. L.","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Institute of Genetics Jacinto Magalh\u00e3es Porto Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Coelho","sequence":"additional","affiliation":[{"name":"Medical Genetics Service HCPA Porto Alegre RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. M.","family":"Gibson","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Departments of Pediatrics, Pathology and Human Genetics Children's Hospital of Pittsburgh and University of Pittsburgh School of Medicine Pittsburgh PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Wajner","sequence":"additional","affiliation":[{"name":"Medical Genetics Service HCPA Porto Alegre RS Brazil"},{"name":"Deparment of Biochemistry ICBS, UFRGS Porto Alegre Brazil"},{"name":"Servi\u00e7o de Gen\u00e9tica M\u00e9dica, HCPA Rua Ramiro Barcelos, 2350 Porto Alegre RS CEP 90.035\u2010903 Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2007,12,17]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"7","article-title":"Mutations underlying 3\u2010hydroxy\u20103\u2010methylglutaryl CoA lyase deficiency in the Saudi population","volume":"16","author":"Al\u2010Sayed M","year":"2006","journal-title":"BMC Med Genet"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2006.067538"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-006-0320-1"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2004.06.003"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1997.0456"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)34944-0"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(76)90160-1"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00441397"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-003-1246-3"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2006.02.009"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00366.2005"},{"key":"e_1_2_6_13_1","first-page":"2327","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Mitchell GA","year":"2001"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1086\/301730"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2004.09.007"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390000363"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01800590"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3230329"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2007.06.020"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpc.2004.12.031"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199509000-00009"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215311"},{"key":"e_1_2_6_23_1","first-page":"143","volume-title":"Techniques in diagnostic human biochemical genetics. A laboratory manual","author":"Sweetman L.","year":"1995"},{"key":"e_1_2_6_24_1","first-page":"1387","volume-title":"Metabolic and molecular bases of inherited disease","author":"Sweetman L","year":"2001"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0188-4409(02)00402-2"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(88)90294-X"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1996.0164"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00540255"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01799652"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-007-0756-y","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T04:30:00Z","timestamp":1694752200000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10545-007-0756-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,12,17]]},"references-count":28,"journal-issue":{"issue":"S3","published-print":{"date-parts":[[2008,12]]}},"alternative-id":["10.1007\/s10545-007-0756-y"],"URL":"https:\/\/doi.org\/10.1007\/s10545-007-0756-y","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,12,17]]}}}