hrp0089fc11.5 | Bone, Growth Plate & Mineral Metabolism 2 | ESPE2018

A Recurrent 6-bp Intronic Deletion in NESP55 with Reduced Penetrance in Pseudohypoparathyroidism Type 1b

Li Dong , Hakonarson Hakon , Levine Michael

Background: Pseudohypoparathyroidism type 1b (PHP1b) is caused by epigenetic errors on the maternal GNAS allele at differentially methylated regions (DMRs) associated with exons A/B, XL, and NESP that lead to reduced production of Gαs transcripts most notably in the renal proximal tubule and thyroid follicular cells. Most PHP1b cases appear sporadically, few of which can be explained by paternal uniparental disomy involving chromosome 20q, leading to global methy...

hrp0089fc2.2 | Bone, Growth Plate & Mineral Metabolism 1 | ESPE2018

Whole Genome Sequencing Reveals Novel Intragenic Deletions of GNAS as Causes of Pseudohypoparathyroidism Type 1a

Li Dong , Bupp Caleb , Hakonarson Hakon , Levine Michael

Background: Pseudohypoparathyroidism type 1a (PHP1a) is characterized by Albright hereditary osteodystrophy (AHO) and multi-hormone resistance, most commonly to parathyroid hormone (PTH) and thyroid-stimulating hormone. This rare disorder is caused by inactivating mutations involving exons 1–13 of the imprinted GNAS gene that encodes the alpha-subunit of the stimulatory G protein (Gαs). Due to paternal imprinting of Gαs transcripts, GNAS mutati...

hrp0084fc2.1 | Bone & Mineral Metabolism | ESPE2015

Whole Exome Sequencing Analysis of Patients with Autosomal Recessive Hypophophatemic Rickets Identified Mutations in DMP1, ENPP1 and SLC34A3

Li Dong , Tenenbaum-Rakover Yardena , Tian Lifeng , Hou Cuiping , Kim Cecilia , Hakonarson Hakon , Levine Michael

Background: Hypophosphatemic rickets (HR) is most commonly X-linked or autosomal dominant, but autosomal recessive (AR) forms have been described. ARHR1 (DMP1) and ARHR2 (ENPP1) share identical biochemical characteristics of excessive renal phosphate wasting due to increased circulating levels of the phosphatonin FGF23 and low serum levels of 1,25(OH)2D. By contrast, in hereditary hypophosphatemic rickets with hypercalciuria (HHRH) phosphaturia is ...

hrp0084fc2.2 | Bone & Mineral Metabolism | ESPE2015

Identification of Mutations in TBX1 and AIRE in Isolated Hypoparathyroidism Patients

Li Dong , Schnellbacher Sarah , Tian Lifeng , Hou Cuiping , Kim Cecilia , Hakonarson Hakon , Levine Michael

Background: Hypoparathyroidism may manifest either as an isolated disorder or as a component of a more complex syndrome. Molecular genetic studies indicate that mutations in PTH, CASR, GCM2 and GNA11 are causes of isolated hypoparathyroidism (IH) and mutations in GATA3, TBCE, FAM111A, AIRE and TBX1 are associated with different complex syndromes with hypoparathyroidism.Objec...

hrp0095p1-220 | Bone, Growth Plate and Mineral Metabolism | ESPE2022

Hypocalcemia as the Initial Presentation of Type2 Bartter Syndrome: A Family Report

London Shira , A. Levine Michael , Li Dong , Spiegel Ronen , Lebel Asaf , Tenenbaum-Rakover Yardena

Context: Bartter syndrome (BS) is a group of rare autosomal-recessive tubulopathies characterized by hypokalemic, hypochloremic metabolic alkalosis in which the primary defect is a deficiency of transporters involved in sodium chloride reabsorption. Type 2 BS results from a defect in the renal outer medullary potassium channel encoded by the KCNJ1 gene. Type 2 BS presents with polyhydramnios, intrauterine growth retardation, prematurity, failure to thrive, pol...

hrp0092p2-146 | Fetal, Neonatal Endocrinology and Metabolism (to include Hypoglycaemia) | ESPE2019

Severe Neonatal Hyperparathyroidism Due to a Novel Homozygous Mutation of the Calcium-Sensing Receptor (CaSR)

hacohen solovitz amir , Tenenbaum-Rakover Yardena , Spiegel Ronen , Weinberger Jeffrey , Gillis David , Goor Zamir Gershon , Levine Michael A. , Almagor Tal

Homozygous loss-of-function mutations of the calcium-sensing receptor gene (CaSR) are associated with neonatal severe hyperparathyroidism (NSHPT), a life-threatening condition with a challenging treatment approach.We report a 7-day-old-female infant who was admitted to our Pediatric Department due to poor sucking. On examination she was lethargic and hypotonic. Laboratory evaluation revealed extreme hypercalcemia of 23.54 mg/dL (N: 7.6–10.4...

hrp0089rfc11.1 | Bone, Growth Plate & Mineral Metabolism 2 | ESPE2018

Diagnosis and Management of Pseudohypoparathyroidism and Related Disorders: First International Consensus Statement

Mantovani Giovanna , Bastepe Murat , Monk David , de Sanctis Luisa , Thiele Susanne , Usardi Alessia , Ahmed Faisal , Bufo Roberto , Choplin Timothee , DeFillipo Gianpaolo , Devernois Guillemette , Eggermann Thomas , Elli Francesca M , Freson Kathleen , Ramirez Aurora Garcia , Germain-Lee Emily , Groussin Lionel , Hamdy Neveen , Hanna Patrick , Hiort Olaf , Juppner Harald , Kamenicky Peter , Knight Nina , Kottler Marie-Laure , Le Norcy Elvire , Lecumberri Beatriz , Levine Michael A , Makiti Outi , Martin Regina , Martos-Moreno Gabriel Angel , Minagawa Masanori , Muray Philip , Pereda Arrate , Pignolo Roberto , Rejnmark Lars , Rodado Rebecca , Rothenbuhler Anya , Saraff Vrinda , Shoemaker Ashley , Shore Eileen M. , Silve Caroline , Turan Serap , Woods Philip , Zillikens M. Carola , de Nanclares Guiomar Perez , Linglart Agnes

Pseudohypoparathyroidism (PHP) and related disorders lead to a wide spectrum of abnormal physical characteristics, neurocognitive and endocrine abnormalities. PHP (including all subtypes), pseudoPHP, acrodysostosis and progressive osseous heteroplasia refer to heterogeneous disorders characterized by physical findings, differently associated in each subtype, including short bones, short stature, stocky build, subcutaneous ectopic ossifications, as well as laboratory abnormalit...