Face-sparing Congenital Generalized Lipodystrophy Type 1 Associated With Nonclassical Congenital Adrenal Hyperplasia

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....

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Published in:The journal of clinical endocrinology and metabolism 2022-09, Vol.107 (9), p.2433-2438
Main Authors: Costa, Sara, Sampaio, Lurdes, Berta Sousa, Ana, Xing, Chao, Agarwal, Anil K, Garg, Abhimanyu
Format: Article
Language:English
Subjects:
ACTH
Acute Disease
Adolescent
Adrenal Hyperplasia, Congenital - complications
Adrenal Hyperplasia, Congenital - drug therapy
Adrenal Hyperplasia, Congenital - genetics
Adrenogenital syndrome
Adult
Antilipemic agents
Child
Child, Preschool
Clinical
Corticosteroids
Development and progression
Drospirenone
Female
Genetic disorders
Glycoproteins
Hemoglobin
Hirsutism - complications
Humans
Hyperglycemia
Hyperinsulinism - complications
Hyperlipidemias - complications
Hypertriglyceridemia - complications
Hypoglycemic agents
Infant, Newborn
Insulin glargine
Insulin glulisine
Lipodystrophy
Lipodystrophy, Congenital Generalized - complications
Lipodystrophy, Congenital Generalized - diagnosis
Lipodystrophy, Congenital Generalized - genetics
Luteinizing hormone
Menstruation
Menstruation Disturbances - complications
Pancreatitis
Pituitary hormones
Progesterone
Puberty, Precocious - complications
Stein-Leventhal syndrome
Steroid 21-Hydroxylase
Young Adult
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Summary: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. 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>C; p.(Leu165_Gln196del), and c.del366_588+534; p.(Leu123Cysfs*55) in AGPAT2 plus c.806G>C; p.(Ser269Thr) and c.844G>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. 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.
ISSN:0021-972X
1945-7197
DOI:10.1210/clinem/dgac406