ESPE Abstracts

Background: Pseudohypoparathyroidism type Ib (PHP-Ib) is due to a maternal loss of GNAS exon A/B methylation and leads to decreased expression of the stimulatory G protein (Gsα) in specific tissues. Evidence suggests an increased incidence of imprinting disorders in children conceived by Assisted Reproductive Technologies (ART). Nevertheless, no associations between ART and PHP – Ib have been found to date.

Clinical case: 7.4-years-old male with history of impaired neurological development. Conceived by ART, born adequate for gestational age. Presented at 4 years of age with a creatine kinase (CK) persistently increased (200–278 IU/l, NV<140). At 6 years an elevated PTH was detected (199 pg/ml NV <60) with normal calcium and alkaline phosphate, normal high phosphorus and a low 25(OH) Vitamin D (18.3 ng/ml). He was asymptomatic and diagnostic work-up excluded systemic diseases, thyroid, adrenal compromise, inborn errors of metabolism, skeletal and chromosomal abnormalities. Physical exam was unremarkable except for a narrow forehead, nasal bridge hypoplasia and micropenis (penile length 3.2 cm, <−2 SDS). His height was at 0.63 SDS, and BMI 1.48 SDS. Vitamin D supplementation increased 25(OH)D to 25.9 ng/ml, but PTH remained high. PHP-Ib was considered but analysis of the microsatellites for the GNAS region on Chr. 20q did not reveal paternal uniparental disomy (patUPD20q). Instead, an almost complete loss of methylation at GNAS exons A/B and AS, and a gain of methylation at exon NESP were found. There were no changes at exon XL and no evidence of a micro deletion within the GNAS/STX16 region. After 1 year of 0.5 ug QD of calcitriol treatment he remains asymptomatic and presents biochemical improvement: 25(OH)D 25.9 ng/ml, calcium 9.5 mg/dl, phosphorus 4.8 mg/dl, PTH 105 pg/ml, and CK 133 UI/l.

Conclusion: We present a patient with PHP – Ib due to impaired methylation at GNAS exons A/B, AS and NESP most likely associated to ART.