SUN-799 Hypercalcemia in a Patient with Limb-Girdle Muscular Dystrophy

Abstract Disclosure: A. Shehaj: None. A. Paracha: None. A. Tall: None. A. Ehsan: None. F. Waqar: None. S. Sridhar: None. A. Siddiqui: None. Introduction: Limb-girdle muscular dystrophy (LGMD) is a genetic disorder that primarily impacts proximal muscles around the hip and shoulder, causing muscle weakness and wasting. The age of onset, severity, and clinical manifestations vary greatly among several genetic subtypes. Serum creatine kinase is usually elevated, and muscle biopsy shows dystrophin-positive muscular dystrophy changes. Systemic features or other organ involvement may be noted, such as cardiomyopathy, arrhythmia, or restrictive lung disease. Nephrocalcinosis and hypercalcemia are not typically associated with this condition. This case highlights a potential complication of this disease that physicians should consider when caring for patients with LGMD. Case Presentation: A 69-year-old woman with history of LGMD, CKD3, nephrolithiasis, NASH and GERD presented for evaluation of osteoporosis and hypercalcemia. Serum calcium was 10.5 mg/dL (8.4-10.2), albumin 4.9 g/dL (3.5-5.2), magnesium 2.2 mg/dL (1.6-2.6), phosphorus 2.9 mg/dL (2.5-4.5), 25-hydroxy vitamin D 41 ng/ml (30-100), 1,25-hydroxy vitamin D 74 pg/ml (19.9-79.3), PTH 26.8 pg/ml (15-65), PTHrP 0.5 pmol/L (<4.2), TSH 1.84 uIU/ml (0.3-4.2), ALP 53 u/L (35-115), 24-hour urine calcium 191 mg/day (100-250). ACE level and SPEP were normal. Renal ultrasound revealed bilateral medullary nephrocalcinosis. On review of previous labs, she had persistent hypercalcemia for more than a decade, with calcium in the 10.5-11 mg/dL range. PTH over several years was in mid normal range of 25-35 pg/ml. She was not on calcium supplements or over-the-counter Tums to suggest exogenous sources. Since extensive work-up was nonrevealing, and all possible etiologies of non-PTH mediated hypercalcemia were ruled out, it was suggested that persistent hypercalcemia and nephrocalcinosis were related to underlying LGMD. Discussion: It has been observed that some forms of muscular dystrophy may be associated with renal dysfunction, nephrolithiasis, hypercalciuria, hypocalciuria or hyperphosphaturia. The exact mechanism is unclear. There is evidence from animal models of calcium homeostasis dysregulation in the skeletal muscle. CAPN3 gene, implicated in some forms of LGMD, has been found to interact with several key calcium handling proteins, such as RyR1, CSQ, and SERCA. Several of these calcium handling proteins may be potential candidates for therapeutic approaches since there is no effective treatment available. Although hypercalcemia and nephrocalcinosis are not typically associated, clinicians should be aware of this possibility, as some patients may be predisposed. This can have implications in evaluation and management of the disease, as well as potential complications. Presentation: Sunday, July 13, 2025