A698 | Journal of the Endocrine Society | doi: 10.1210/jendso/bvaa046 A698 JESOCI, Volume 4, Abstract Supplement, 2020 syndrome usually presents with neurological symptoms such as seizures, tetany, speech impairment, dementia, de- terioration of intelligence, involuntary movements. The eti- ology of Fahr syndrome is mostly associated with endocrine disorders especially hypoparathyroidism either primary or secondary or pseudo hyperparathyroidism; including adult onset neurodegenerative conditions, infectious disease like intrauterine and perinatal infections or inherited congen- ital causes are also considered. Clinical Case The authors report a 33-year-old Ethiopian female not known to any medical illness presented with abnormal involuntary left-hand movement, headache and dizzi- ness. Further examination shows positive Chvostek’s and Trousseau’s signs. In addition, laboratory findings reveal decreased levels of serum calcium (1.227 mmol/L, normal range of 2.2-2.65 mmol/L), serum albumin (33.53 mg/ dL, normal range of 35-52 g/L) and parathyroid hormone (0.3pmol/L, normal range of 1.1-8.43 pmol/L), decreased vitamin D serum level (14.52 ng/ml, normal range of 30-75 ng/ml). Interestingly, brain imaging shows bilateral symmetrical subcortical white matter, basal ganglia, cere- bellar dentate nuclei calcifications. Thus, Fahr syndrome diagnosis was made. She was promptly treated with cal- cium and vitamin D replacement. Calcium gluconate was given intravenously with oral calcium carbonate and oral cholecalciferol. The patient recovered with this treatment leading to positive results without any recurring symptoms. INTERNAL Conclusion In conclusion, Fahr syndrome is a rare sequel of hypopara- thyroidism, mostly presented with neurological symptoms due to hypocalcemia which after correction subdues the occurring manifestation such as in this case presented. Early diagnosis of Fahr syndrome due to hypoparathy- roidism is crucial for prompt treatment and reversal of symptoms also to prevent complications. INTERNAL Pediatric Endocrinology PEDIATRIC SEXUAL DIFFERENTIATION, PUBERTY, AND BONE BIOLOGY Clinical and Hormonal Features of 37 Families with Central Precocious Puberty Due to MKRN3 Loss-Of -Function Mutations Carlos Eduardo Seraphim, MD 1 , Ana Pinheiro Machado Canton, PhD 1 , Luciana Ribeiro Montenegro, BSC 1 , Maiara Ribeiro Piovesan, BSC 1 , Tabata Mariz Bohlen, BSC 2 , Renata Frazao, PhD 2 , Delanie Bulcão Macedo, MD, PhD 3 , Aline Guimarães de Faria, MD 1 , Carolina Ramos, MD 1 , Priscila Carvalho Gagliardi, MD 4 , Ana Paula Abreu, MD, PhD 3 , Andrea de Castro Leal, MD 1 , Margaret De Castro, MD, PHD 5 , Sonir Roberto Rauber Antonini, PHD,MD 5 , Leandro Soriano-Guillén, MD 6 , Arancha Escribano-Muñoz, MD 7 , Raquel Corripio Collado, MD 8 , Jose Ignacio Labarta, MD 9 , Travieso-Suárez Lourdes, MD 10 , Neimar Valentina Ortiz-Cabrera, MD 11 , Jesús Argente, MD, PhD 12 , Berenice Bilharinho Mendonca, MD 1 , Ursula B. Kaiser, MD 13 , Vinicius Nahime Brito, MD 1 , Ana Claudia Latronico, MD 1 . 1 Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM/42, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil, 2 Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil, 3 Brigham and Women’s Hospital/Harvard Medical School, Boston, MA, USA, 4 Nemours Children’s Health System, Jacksonville, FL, USA, 5 Ribeirao Preto Medical School - University of Sao Paulo, Ribeirão Preto, Brazil, 6 Department of Paediatrics, IIS-Fundación Jiménez Díaz, UAM, Madrid, Spain, 7 Servicio de Endocrinología, Hospital Infantil Universitario Niño Jesús, Madrid, España; Departamento de Pediatría, Universidad Autónoma de Madrid, Madrid, Spain, 8 Hospital Universitario Parc Tauli, Barcelona, Spain, 9 Endocrinology Unit, Children’s Hospital Miguel Servet, University of Zaragoza, Zaragoza, Spain, 10 Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Madrid, Spain, 11 Department of Clinical Genetics, Hospital Infantil Universitario Niño Jesús, Madrid, Spain, 12 University Hospital Nio Jess & Universidad Autnoma de Madrid, Madrid, Spain, 13 Brigham and Women’s Hospital, Boston, MA, USA. SUN-085 Context: Loss-of-function mutations in the maternally imprinted Makorin RING-finger 3 (MKRN3) gene (15q11.2) are the most prevalent cause of familial central precocious puberty (CPP). Objectives: To analyze the phenotypes of a large cohort of children with CPP due to MKRN3 mutations and to compare them with the phenotypes of idiopathic CPP. Setting and Participants: We studied 73 individuals from 37 families with mutations in MKRN3 originating from nine different countries. The phenotypes of these patients at ini- tial diagnosis were compared to a cohort of 124 patients with idiopathic CPP. Additionally, expression of nine different genes implicated with pubertal timing, including MKRN3, was performed in the hypothalamus of female mice in dif- ferent phases of sexual maturation. Results: Nineteen dif- ferent heterozygous, paternally inherited mutations in MKRN3 were identified in 73 patients with CPP (48 girls and 25 boys). Six MKRN3 mutations were frameshifts, one introduced a premature stop codon, 11 were missense mutations predicted to be pathogenic, and one was a dele- tion in the promoter region. A frameshift mutation affecting codon 161 in the amino terminal region of the protein was the most frequent MKRN3 defect (46%), representing a hotspot region. Among the cohort with MKRN3 mutations, first pubertal signs occurred at 6·2 ± 1·2 years in girls and 7·6 ± 1·4 years in boys. Patients harboring severe frameshift/ nonsense mutations did not differ significantly in any clin- ical or hormonal parameters compared to the 20 patients with missense variants. However, when the 48 girls with MKRN3 mutations were compared with 124 idiopathic CPP girls, some parameters could be considered as possible predictors of the genetic cause: a lower age at first medical appointment (7·1 ± 1·1 in the MKRN3 group vs. 8·0 ± 2 years in the idiopathic group; p< 0.001) and a shorter time interval between puberty onset and medical assistance (0·8 ± 0·8 vs 2·2 ± 2·1 years; p< 0.001). Interestingly, the other predictor of MKRN3 mutations was a higher basal FSH level (5·1 ± 2·3 vs 3·9 ± 2·7 IU/L; p = 0.017) at first evaluation, although no cutoff value yielded good accuracy. Patients originating from European/Mediterranean countries were more likely to have missense variants (56% of all mutations) than North American and South American (23%) counterparts (p <0.001). Mouse Mkrn3 mRNA levels in the arcuate nu- cleus were highest in the prepubertal phase when compared Downloaded from https://academic.oup.com/jes/article/4/Supplement_1/SUN-085/5833045 by guest on 02 October 2023