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

CONTEXT: 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. CASE DESCRIPTION: 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. CONCLUSION: 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.

Klinefelter's Syndrome: 18 years experience of a pediatric endocrinology unit / Síndrome de Klinefelter: 18 anos de experiência de uma unidade de endocrinologia pediátrica

Methods: A cross-sectional retrospective study was conducted, based on clinical data of patients diagnosed with Klinefelter Syndrome and followed from January 1992 to December 2009 (18 years) at a Pediatric Endocrinology Unit of a tertiary care-level hospital in Portugal.Results: In the study period 15 patients were identified. Seven had a positive prenatal diagnosis of Klinefelter Syndrome and eight had post-natal diagnosis, after investigation for psychomotor development delay, behavioral disruptions and/or suggestive phenotype (four of them only diagnosed during adolescence). Thirteen patients had a peripheral blood karyotype of 47, XXY and two presented 47, XXY/46, XY mosaicism. The median age of first visit was seven years. Onset of puberty occurred spontaneously in seven cases. Puberty induction was performed in three patients, at age of 14 years. Those who needed hormone treatment had an effective response with no side effects. Behavioral and social inadequacies were identified in two cases and moderate global motor developmental delay in nine. Hyperactivity and attention deficit disorder were diagnosed in five patients, currently treated with methylphenidate.Conclusions: A global motor development delay together with physical features of Klinefelter Syndrome in a child justifies karyotyping given the high prevalence of this syndrome, especially if socialization problems and learning difficulties are present. This study highlights the need for greater awareness in diagnosis as well as the importance of multidisciplinary approach in the care and education of these patients.

Objetivos: descrever as características clínicas de crianças e adolescentes com Síndrome de Klinefelter.Métodos: foi realizado um estudo transversal retrospectivo, com base em dados clínicos dos pacientes com diagnóstico de Síndrome de Klinefelter acompanhados entre janeiro de 1992 e dezembro de 2009 (18 anos) na Unidade de Endocrinologia Pediátrica de um hospital de cuidados terciários em Portugal.Resultados: foram identificados 15 pacientes no período do estudo. Sete tiveram diagnóstico positivo pré-natal de Síndrome de Klinefelter e oito tiveram o diagnóstico pós-natal, após investigação por atraso no desenvolvimento psicomotor, distúrbios comportamentais e / ou fenótipo sugestivo (quatro deles diagnosticados apenas durante a adolescência). Treze pacientes tinham um cariótipo de sangue periférico de 47, XXY e dois apresentaram 47, XXY/46, mosaicismo XY. A idade mediana da primeira visita foi de sete anos. Início da puberdade ocorreu espontaneamente em sete casos. Indução da puberdade foi realizada em três pacientes, com a idade de 14 anos. Aqueles que precisaram de tratamento hormonal tiveram uma resposta eficaz, sem efeitos colaterais. Inadequações comportamentais e sociais foram identificadas em dois casos e atraso moderado de desenvolvimento motor global em nove. Hiperatividade e transtorno de déficit de atenção foram diagnosticados em cinco pacientes, atualmente tratados com metilfenidato.Conclusões: atraso global do desenvolvimento, juntamente com características físicas da Síndrome de Klinefelter em uma criança, justifica a solicitação de cariótipo, dada a elevada prevalência dessa síndrome, especialmente se estiveram presentes problemas de socialização e dificuldades de aprendizagem. Este estudo destaca a necessidade de uma maior conscientização para o diagnóstico, bem como a importância da abordagem multidisciplinar no cuidado e na educação desses pacientes.