Neuromuscular symptoms in a patient with familial pseudohypoparathyroidism type Ib diagnosed by methylation-specific multiplex ligation-dependent probe amplification

Endocrine Journal

Shuichi Tsuchiya²  Akihiko Saitoh³  Keisuke Nagasaki¹  Tsutomu Ogata¹  Maki Fukami¹ 

[1] Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan;Department of Pediatrics, Ojiya general Hospital, Niigata 947-8641, Japan;Division of Pediatrics, Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan

关键词: Pseudohypoparathyroidism type Ib (PHP-Ib);    Neuromuscular symptoms;    Hypocalcemia;    STX16;    Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA);   

DOI  :  10.1507/endocrj.EJ12-0257

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(12)Pseudohypoparathyroidism type Ib (PHP-Ib) is a rare genetic disorder characterized by hypocalcemia and hyperphosphatemia due to imprinting defects in the maternally derived GNAS allele.Patients with PHP-Ib are usually identified by tetany, convulsions, and/or muscle cramps, whereas a substantial fraction of patients remain asymptomatic and are identified by familial studies.Although previous studies on patients with primary hypoparathyroidism have indicated that hypocalcemia can be associated with various neuromuscular abnormalities, such clinical features have been rarely described in patients with PHP-Ib.Here, we report a 12-year-old male patient with familial PHP-Ib and unique neuromuscular symptoms.The patient presented with general fatigue, steppage gait, and myalgia.Physical examinations revealed muscular weakness and atrophies in the lower legs, a shortening of the bilateral Achilles’ tendons and absence of deep tendon reflexes.Laboratory tests showed hypocalcemia, hyperphosphatemia, elevated serum intact PTH level, and impaired responses of urinary phosphate and cyclic AMP in an Ellsworth-Howard test, in addition to an elevated serum creatine kinase level.Clinical features of the patient were significantly improved after 1 month of treatment with alfacalcidol and calcium.Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and subsequent PCR analyses identified a methylation defect at exon A/B of GNAS and a microdeletion involving exons 4-6 of the GNAS neighboring gene STX16 in the patient and in his asymptomatic brother.The results suggest that various neuromuscular features probably associated with hypocalcemia can be the first symptoms of PHP-Ib, and that MS-MLPA serves as a powerful tool for screening of GNAS abnormalities in patients with atypical manifestations.

【 授权许可】

Unknown