Pseudohypoparathyroidism: phenotypic spectrum in kindred
© Natino and Vasanwala; licensee BioMed Central Ltd. 2015
Published: 28 April 2015
Pseudohypoparathyroidism (PHP) encompasses a heterogeneous group of disorders due to an inactivating mutation in the GNAS gene which encodes the α subunit of Gs proteins (Gsα). Gsα plays a crucial role in intracellular signal transduction of peptides, hormones and neurotransmitter receptors in multiple tissues. Key features of PHP include Albright Hereditary Osteodystrophy (AHO) and biochemical evidence of multiple hormone resistances. There are several conflicting mechanisms for its heterogeneity; a possible explanation is a tissue-specific differential imprinting of Gsα protein. PHP type1a has AHO with multiple hormone resistance and is inherited as maternal imprinting defect. PHP type 1b presents with hormone resistance but no AHO features and is probably due to epigenetic methylation defects. Peudopseudohypoparathyroidism is another subtype with AHO but absence of hormone resistance and is inherited as paternal inactivating mutation. We describe a family with female members having PHP with variable clinical and biochemical features.
(136cm, - 4.05 SDS)
(134cm, -2.84 SDS)
(145cm, -2.79 SDS)
(32.44 kg/m2,+2.04 SDS )
Cognitive dysfunction with need for special school
PTH (0.9 -6.2pmol/L)
Phosphate (1.0-1.8 mmol/L)
TSH (0.50-4.50 mIU/L)
The two patients with PHP described above had an interesting presentation as congenital hypothyroidism with features of AHO evolving later in life. They exhibit clinical evidence of maternal transmission with end-organ resistance. This family illustrates heterogeneity of presentation of GNAS mutation.
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