Introduction: Pseudohypoparathyroidism is a heterogeneous disease characterized by hypocalcemia, hyperphosphatemia and parathyroid hormone resistance. The distinct pseudohypoparathyroidism types are distinguished by physical features, the coexistence of other hormone resistances and genetic defects. Pseudohypoparathyroidism type Ib is more often associated with sporadic cases, unlike others types.
Clinical Case: Male, born in France, diagnosed with pseudohypoparathyroidism during childhood. There was a history of fatigue, gait disorder and delayed eruption of teeth. Laboratory investigation revealed serum hypocalcemia, hyperphosphatemia and elevated serum PTH levels. No family history of phosphocalcium metabolism disorder. He was treated with oral calcium and cholecalciferol. At the age of 9, he starts living in Portugal. Physical examination showed no features of Albright Hereditary Osteodystrophy. Laboratory results showed normal thyroid function and no evidence of other hormone resistances. He started treatment with calcitriol also in addition to oral calcium and cholecalciferol. Over the years, the goal to an adequate calcium-phosphate level was difficult to obtain in this patient due to poor treatment adherence. At 34 years old, urinary calculi was detected on renal ultrasonography. 7 years later, head computerized tomography revealed extensive calcifications at the level of the cerebellar hemispheres, lenticular nuclei, corona radiata, centra semiovale and subcortical level, suggestive of Fahrs syndrome. He was referred to a geneticist and the molecular genetic result revealed a GNAS gene methylation defect specifically in 20q13.32 region performed by MS-MLPA analysis. STX16 deletion was not detectable. This result confirms the diagnosis of pseudohypoparathyroidism type Ib caused by a paternal uniparental disomy of the long arm of chromosome 20.
Conclusions: The molecular investigation is not essential for the therapeutic approach. In this patient, the identification of a methylation defect in a region of GNAS gene was useful for the classification of pseudohypoparathyroidism and allowed us to evaluate this case as a sporadic event, therefore without specific risk for the patients offspring. The present case also serves to emphasize the importance of treatment adherence that may prevent acute and chronic complications of hypocalcemia.
21 May 2022 - 24 May 2022