MON-395 Severe Osteoporosis in a 31-year-old woman with MMP13 mutation of uncertain significance

Abstract A.Y. Groysman: None. A. Poloju: None. P. Majety: None. M. Cheifetz: None. Severe Osteoporosis in a 31-year-old woman with MMP13 mutation of uncertain significance Introduction/background: We report a case of severe osteoporosis and dental agenesis in a young woman, possibly related to Matrix Metalloproteinase 13 (MMP13) gene mutation of uncertain significance. MMP13 gene mutations have been associated with metaphyseal anadysplasia, including spondyloepimetaphyseal dysplasia. Clinical case:A 31-year-old G1P1 white woman presented with acute onset back pain three months postpartum. Her delivery was complicated by hemorrhage due to uterine atony. She had no history of trauma. She was found to have thoracic vertebral compression fractures at T9 and T11. She retained her primary teeth but had no spontaneous eruption of permanent teeth and required dental implants. She was unable to gain weight despite consuming 3000 calories per day for many years. She was never diagnosed with any eating disorders. Calcium intake was low (<1 serving dairy per day). Menstrual history was notable for menarche at age 15 and had regular periods. No history of infertility. Family history is significant for hyperparathyroidism and osteoporosis with a hip fracture at age 50 in her mother. She is 5’2’’ tall with a BMI of 14.5. Bone density scan showed Z-scores of -4.0 at the lumbar spine, -3.6 at the femoral neck, and -3.2 at the total hip. Workup showed Vitamin D 33 ng/ml (30- 100 ng/ml), TSH 1.35 mIU/L (0.28-4.10 mIU/L), calcium 10.2 mg/dL (8.8-10.6 mg/dL), eGFR >60, parathyroid hormone 42 pg/mL (12-88 pg/mL), phosphorus 3.7 mg/dl (2.5-4.5 mg/dL), 24-hour urine calcium/g creatinine 210 with urine volume 2100cc, tryptase 5.8mcg/L (<11 mcg/L), C-telopeptide 711 pg/ml (60-650 pg/ml), alkaline phosphatase 122 U/L (35-104U/L), 17 beta-estradiol 51 pg/mL, FSH 3.4 mIU/mL, tissue transglutaminase IgA 3.04 (<20), normal serum protein electrophoresis and light chain analysis. There was no clinical suspicion of hypercortisolism. A skeletal disorders panel for 358 genes identified a pathogenic variant in TUBGCP6 and a variant of uncertain significance (Exon 9, c.1214A>6 (p.Tyr40SCys) in the MMP13 gene. TUBGCP6 has been associated with microcephaly and chorioretinopathy, which our patient did not have. She started treatment with calcium, vitamin D, and Teriparatide. She took Teriparatide for two months without fracture but had to discontinue due to an unexpected pregnancy. Conclusions: This is the first case demonstrating the possible role of MMP13 mutation in the development of severe osteoporosis. Contributing risk factors in our patient include a family history of osteoporosis, possible failure to accrue peak bone mass due to lifelong underweight status, limited dietary calcium intake, and late onset of menarche, in addition to recent pregnancy and lactation. However, this patient’s dental agenesis along with severe osteoporosis raises the possibility that an underlying genetic mutation in MMP13 is contributing. Monday, June 3, 2024