Clinical and Molecular Characteristics and Long-term Follow-up of Children With Pseudohypoparathyroidism Type IA

Hanna Ludar, Yael Levy-Shraga, Osnat Admoni, Hussein Majdoub, Kineret Mazor Aronovitch, Ilana Koren, Shoshana Rath, Ghadir Elias-Assad, Shlomo Almashanu, Giovanna Mantovani, Orit Pinhas Hamiel, Yardena Tenenbaum-Rakover

Research output: Contribution to journalArticlepeer-review


CONTEXT: Pseudohypoparathyroidism type IA (PHPIA) is a rare genetic disorder characterized by hormone resistance and a typical phenotype named Albright hereditary osteodystrophy. Unawareness of this rare disease leads to delays in diagnosis. OBJECTIVE: The aims of this study were to describe the clinical and molecular characteristics of patients with genetically confirmed GNAS mutations and to evaluate their long-term outcomes. METHODS: A retrospective search for all patients diagnosed with PHPIA in 2 referral centers in Israel was conducted. RESULTS: Nine children (8 females) belonging to 6 families were included in the study. Five patients had GNAS missense mutations, 2 had deletions, and 2 had frameshift mutations. Four mutations were novel. Patients were referred at a mean age of 2.4 years due to congenital hypothyroidism (5 patients), short stature (2 patients), or obesity (2 patients), with a follow-up duration of up to 20 years. Early obesity was observed in the majority of patients. Elevated parathyroid hormone was documented at a mean age of 3 years; however, hypocalcemia became evident at a mean age of 5.9 years, about 3 years later. All subjects were diagnosed with mild to moderate mental retardation. Female adult height was very short (mean -2.5 SD) and 5 females had primary or secondary amenorrhea. CONCLUSION: Long-term follow-up of newborns with a combination of congenital hypothyroidism, early-onset obesity, and minor dysmorphic features associated with PHPIA is warranted and molecular analysis is recommended since the complete clinical phenotype may develop a long time after initial presentation.

Original languageEnglish
Pages (from-to)424-438
Number of pages15
JournalJournal of Clinical Endocrinology and Metabolism
Issue number2
StatePublished - 18 Jan 2024


  • Albright hereditary osteodystrophy AHO
  • GNAS gene
  • PHP
  • hypocalcemia
  • hypothyroidism
  • pseudohypoparathyroidism


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