Progressive osseous heteroplasia, as an isolated entity or overlapping with Albright hereditary osteodystrophy

Maria H. Lin 1 , Nawaporn Numbenjapon 2 , Emily L. Germain-Lee and Pisit Pitukcheewanont 1
  • 1 Center for Endocrinology, Diabetes, and Metabolism, Children’s Hospital Los Angeles, Los Angeles, CA, USA
  • 2 Division of Endocrinology, Diabetes, and Metabolism, Department of Pediatrics, Phramongkutklao Hospital, Bangkok, Thailand
  • 3 Albright Clinic, Kennedy Krieger Institute, Baltimore, MD, USA
  • 4 Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Maria H. Lin, Nawaporn Numbenjapon, Emily L. Germain-Lee and Pisit Pitukcheewanont

Abstract

Introduction: Progressive osseous heteroplasia (POH) is a condition of invasive heterotopic ossification. Reports of patients with mild POH with Albright hereditary osteodystrophy (AHO), specifically pseudohypoparathyroidism type Ia (PHP Ia) with hormonal resistance, suggest the possibility of a common molecular basis. GNAS has been implicated to account for overlapping features of POH and PHP Ia.

Case 1: A 4-year-old boy with obesity, speech delay, and expanding subcutaneous masses on buttock/forearm. Physical exam revealed round facies and brachydactyly. Blood tests showed normal Ca, P, Mg, 25-OH vitamin D levels but elevated parathyroid hormone (PTH) and thyroid-stimulating hormone (TSH). Abdominal computed tomography (CT) showed areas with calcifications in the subcutaneous tissue, fat, and muscle. Pathology of excised tissue revealed ossifications. Genomic study revealed no GNAS mutation. He had POH and PHP Ia.

Case 2: A 3-year-old boy with painful ossifications in the left lower extremity. Lab tests were notable for elevated PTH and high-normal TSH. The CT-scan showed subcutaneous/intramuscular calcifications. Genetic testing showed GNAS mutation in exon 12 [c.1024C>T (R342X)]. Patient had POH and PHP Ia.

Case 3: A 9-year-old boy with knee pain and subcutaneous ossifications in back and upper/lower extremity, causing significantly limited joint mobility. Lab tests were normal. The CT-scan showed areas corresponding to subcutaneous/intramuscular ossifications throughout torso and extremities, consistent with POH. There was no GNAS mutation.

Conclusions: Patients with heterotopic ossifications present with a wide spectrum of disease. Although GNAS-based mutations have been postulated to account for overlapping features of AHO and POH, normal DNA studies in certain patients with POH/AHO suggest that there may exist other molecular/epigenetic mechanisms explaining their overlapping features.

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The Journal of Pediatric Endocrinology and Metabolism (JPEM) is the only international journal dedicated exclusively to endocrinology in the neonatal, pediatric and adolescent age groups, and publishes the results of clinical investigations in pediatric endocrinology and basic research. JPEM publishes Review Articles, Original Research, Case Reports, Short Communications and Letters to the Editor.

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