Category: Calcium/Bone Disorders

Monitor: 25

25 - ABNORMAL BIOLOGIC MINERALIZATION: A CASE OF PSEUDO-PSEUDOHYPOPARATHYROIDISM ASSOCIATED WITH ECTOPIC CALCIFICATION, GOUT, AND SYNOVIAL CHONDROMATOSIS

Friday, Apr 26
11:00 AM – 11:30 AM

Objective : Pseudo-pseudohypoparathyroidism (PPHP) shows characteristics of Albright’s hereditary osteodystrophy (AHO) that is found in patients with pseudohypoparathyroidism without the parathyroid resistance syndrome and associated laboratory abnormalities of hyperparathyroidism, hypocalcemia, hyperphosphatemia, and low calcitriol levels. Our case is the first to our knowledge of a patient with PPHP with AHO who has gout and synovial chondromatosis.


Methods : n/a


Results : n/a


Discussion :


Case Presentation: The patient is a 39 year-old male with history of PPHP, type 2 diabetes, hypertension, hyperlipidemia, fatty liver, obesity, gout (diagnosed on arthrocentesis), and osteoma cutis. He has normal cognition and no known family history of PPHP. Patient had prior surgical removal of calcium deposits in his right foot to alleviate pain. Recent history was notable for increasing subcutaneous skin calcifications and worsening chronic right knee pain. Physical exam was notable for characteristics of AHO, including short stature, obesity, rounded facies, soft tissue calcifications, and shortened digits. Labs were unremarkable with normal levels of parathyroid hormone (PTH), calcium, and phosphorus. Hand x-rays showed shortened first distal phalanges, fourth metacarpals, and fifth middle phalanges. Genetic testing revealed a c.636delC frameshift mutation in exon 8 of the GNAS gene. MRI of the right knee showed innumerable intra-articular, ossified loose bodies, highly suggestive of primary synovial chondromatosis. The patient was continued on allopurinol by rheumatology, and referred to orthopedics for removal of loose bodies and synovectomy.



Discussion: PPHP is due to mutation of the GNAS locus on chromosome 20, which encodes the alpha subunit of the adenylate cyclase stimulatory G protein that plays an important role in osteogenesis and undergoes parent-specific methylation. As the kidney primarily expresses the maternal allele, mutation in the maternal allele leads to pseudohypoparathyroidism and PTH resistance. Mutation in the paternal allele results in PPHP and haploinsufficiency in the bone, leading to the AHO phenotype without biochemical abnormalities. Our case reveals a rare association of PPHP with gout and synovial chondromatosis, which is an uncommon, benign condition that leads to synovial metaplasia and ectopic foci of cartilage. This case highlights the importance of genetics/epigenetics in skeletal health, independent of calcium homeostasis in the blood.


Conclusion :

Though patients with PPHP typically are thought to not require specific treatment given their normal calcium homeostasis, this case emphasizes the need for a close, multidisciplinary follow up for musculoskeletal complications.

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Jane Rhyu

Fellow
Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, David Geffen School of Medicine at UCLA and VA Greater Los Angeles Healthcare Systems, Los Angeles, CA
Los Angeles, California

UCLA Endocrinology Fellow

Julie Bernthal

Fellow
Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, David Geffen School of Medicine at UCLA and VA Greater Los Angeles Healthcare Systems, Los Angeles, CA

UCLA Endocrinology Fellow

Shalini Bhat

Assistant Professor of Medicine, David Geffen School of Medicine at UCLA
Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, David Geffen School of Medicine at UCLA and VA Greater Los Angeles Healthcare Systems, Los Angeles, CA

Assistant Professor of Medicine, David Geffen School of Medicine at UCLA