{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T07:03:11Z","timestamp":1760598191791,"version":"3.37.3"},"reference-count":25,"publisher":"The Endocrine Society","issue":"9","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-DK105448"],"award-info":[{"award-number":["R01-DK105448"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019481","name":"Southwestern Medical Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019481","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Congenital generalized lipodystrophy, type 1 (CGL1), due to biallelic pathogenic variants in AGPAT2, is characterized by the near total loss of body fat from the face, trunk, and extremities. Patients develop premature diabetes, hypertriglyceridemia, hepatic steatosis, and polycystic ovary syndrome. However, sparing of the facial fat and precocious pubertal development has not been previously reported in CGL1.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Case Description<\/jats:title>\n                  <jats:p>We report a 21-year-old woman of European descent with CGL1 who had sparing of the facial fat and premature thelarche at birth with premature pubarche and menstrual bleeding at age 3 years. Her serum 17-OH progesterone level rose to 1000 ng\/dL (30.26 nmol\/L) after cosyntropin stimulation test, suggestive of nonclassical congenital adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency. Hydrocortisone replacement therapy from age 3.5 to 10 years resulted in cessation of menstruation and growth of pubic hair, and a reduction of breast size. Sanger and whole-exome sequencing revealed compound heterozygous variants c.493-1G&amp;gt;C; p.(Leu165_Gln196del), and c.del366_588+534; p.(Leu123Cysfs*55) in AGPAT2 plus c.806G&amp;gt;C; p.(Ser269Thr) and c.844G&amp;gt;T; p.(Val282Leu) in CYP21A2. She developed diabetes at age 13 requiring high-dose insulin and had 7 episodes of acute pancreatitis due to extreme hypertriglyceridemia in the next 5 years. Metreleptin therapy was initiated at age 18 and after 3 years, she had remission of diabetes and hypertriglyceridemia; however, menstrual irregularity and severe hirsutism did not improve.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Concomitant NCAH in this CGL1 patient was associated with precocious pubertal development and sparing of facial fat. Metreleptin therapy drastically improved her hyperglycemia and hyperlipidemia but not menstrual irregularity and hirsutism.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgac406","type":"journal-article","created":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T17:18:57Z","timestamp":1658337537000},"page":"2433-2438","source":"Crossref","is-referenced-by-count":6,"title":["Face-sparing Congenital Generalized Lipodystrophy Type 1 Associated With Nonclassical Congenital Adrenal Hyperplasia"],"prefix":"10.1210","volume":"107","author":[{"given":"Sara","family":"Costa","sequence":"first","affiliation":[{"name":"Paediatric Endocrine Unit, Department of Pediatrics, Hospital de Santa Maria\/CHULN , 1649-035 Lisbon , Portugal"}]},{"given":"Lurdes","family":"Sampaio","sequence":"additional","affiliation":[{"name":"Paediatric Endocrine Unit, Department of Pediatrics, Hospital de Santa Maria\/CHULN , 1649-035 Lisbon , Portugal"}]},{"given":"Ana","family":"Berta Sousa","sequence":"additional","affiliation":[{"name":"Genetics Service, Department of Pediatrics, Hospital de Santa Maria\/CHULN , 1649-035 Lisbon , Portugal"}]},{"given":"Chao","family":"Xing","sequence":"additional","affiliation":[{"name":"Eugene McDermott Center for Human Growth and Development, Department of Bioinformatics, and Department of Population and Data Sciences, UT Southwestern Medical Center , Dallas, Texas 75390-8591 , USA"}]},{"given":"Anil K","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Division of Nutrition and Metabolic Diseases, Department of Internal Medicine and the Center for Human Nutrition, UT Southwestern Medical Center , Dallas, Texas 75390-8537 , USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7209-6986","authenticated-orcid":false,"given":"Abhimanyu","family":"Garg","sequence":"additional","affiliation":[{"name":"Division of Nutrition and Metabolic Diseases, Department of Internal Medicine and the Center for Human Nutrition, UT Southwestern Medical Center , Dallas, Texas 75390-8537 , USA"}]}],"member":"80","published-online":{"date-parts":[[2022,7,20]]},"reference":[{"key":"2022081816084631300_CIT0001","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/nrendo.2015.123","article-title":"Congenital generalized lipodystrophies--new insights into metabolic dysfunction","volume":"11","author":"Patni","year":"2015","journal-title":"Nat Rev Endocrinol."},{"key":"2022081816084631300_CIT0002","first-page":"358","article-title":"Peculiar distribution of adipose tissue in patients with congenital generalized lipodystrophy","volume":"75","author":"Garg","year":"1992","journal-title":"J Clin Endocrinol Metab."},{"key":"2022081816084631300_CIT0003","first-page":"3077","article-title":"Postmortem findings in congenital generalized lipodystrophy","volume":"80","author":"Chandalia","year":"1995","journal-title":"J Clin Endocrinol Metab."},{"key":"2022081816084631300_CIT0004","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/S0022-3476(79)80087-6","article-title":"Congenital lipodystrophy. 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