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Pseudohypoparathyroidism Type Ib (PHP-Ib): PTH-Resistant Hypocalcemia and Hyperphosphatemia Due to Abnormal GNAS Methylation

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Abstract

Pseudohypoparathyroidism type Ib (PHP-Ib) is a rare disorder characterized by PTH resistance in the proximal renal tubules, which leads to hypocalcemia, hyperphosphatemia, and an elevated serum PTH level. Resistance to other hormones that mediate their actions through G protein-coupled receptors and evidence for AHO can also be observed but are much less frequently than in pseudohypoparathyroidism type Ia (PHP-Ia). Most variants of PHP-Ib are associated with GNAS methylation changes, thereby reducing maternal expression of the stimulatory G protein (Gsα) in few tissues, where paternal expression of this signaling protein is silenced through as-of-yet unknown mechanisms. In familial PHP-Ib cases, these epigenetic changes are caused by deletions within or upstream of GNAS. Duplication of large portions of the paternal chromosome 20q is observed in a few patients with the sporadic form of the disease, but most of these PHP-Ib cases remain undefined at the molecular level.

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  1. Endocrine Unit and Pediatric Nephrology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA

    Harald Jüppner

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  1. Unit of Metabolic and Bone Diseases, University of Florence, Florence, Italy

    Maria Luisa Brandi

  2. Division of Endocrinology, Diabetes and Hypertension, Harvard Medical School and Brigham & Women's Hospital, Boston, Massachusetts, USA

    Edward Meigs Brown

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Jüppner, H. (2015). Pseudohypoparathyroidism Type Ib (PHP-Ib): PTH-Resistant Hypocalcemia and Hyperphosphatemia Due to Abnormal GNAS Methylation. In: Brandi, M., Brown, E. (eds) Hypoparathyroidism. Springer, Milano. https://doi.org/10.1007/978-88-470-5376-2_34

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