A rare disease: Familial hyperphosphatemic tumoral calcinosis

INTRODUCTION: Tumoral calcinosis (TC) is a rare disease characterized by soft tissue calcification as a result of repetitive trauma and prolonged pressure in periarticular areas of large joints; such as hip, knee, shoulder and elbow. There are three different forms; sporadic, familial and secondary TC due to chronic renal diseases, vitamin D hypervitaminosis. Familial hyperphosphatemic TC, which will be presented in this case, causes by relative deficiency or resistance of FGF-23, which is the critical regulatory hormone in the phosphorus metabolism. CLINICAL CASE: A 38-year-old male patient was referred from the nephrology department for hyperphosphatemia. He underwent 14 operations mass lesions, which were painful, progressively enlarging, in the different regions. His first operation at the age of 11 for a lesion in the right knee. Pathologic diagnoses of surgical specimens were reported as tumoral calcinosis. The patient was followed up by different orthopedic clinics from the age of 11, and was operated as new masses appeared. He does not have any complaints other than the pain in the periods when the lesions appear. He has 4 siblings without any known diseases, and his parents were third degree consanguineous. In physical examination, blood pressure was 115/72 mmHg, pulse was 76/min, and temperature was 36.7°C. Her height was 183 cm, and weight was 82 kg, BMI: 24.5 kg/m2. In laboratory tests, serum calcium 10.1 mg/dl, serum phosphate 6,8 mg/dl, parathormone 25 pg/ml, 25-OH Vitamin D 19 ng/ml, creatinine 0.9 mg/dl, alkaline phosphatase 71 U/l, 24-h urinary calcium 129 mg/day and 24-h urinary phosphate 205 mg/day. Bone mineral density at the femoral neck was 1.258 g/cm2, Z score was -1.6, and BMD at the lumbar spine was 1.081 g/cm2, Z score was -0.9. In bone survey, we detected that mild right-facing rotoscoliosis in the thoracolumbar region, increased calcification of the costosternal cartilages, osteophytic tapering in the thoracic region, intracranial calcification in the parietal region, L3-L4 level syndesmophyte, irregularity and adjacent soft tissue calcification at the distal phalanx level of the first toe of the right and left foot (Fig 1). We recommended the patient to avoid trauma and a low phosphorus diet. Maintenance dose vitamin D replacement and phosphorus-binding treatment (calcium-asetate 700 mg 3×2) with meals were started. When phosphate reduction could not be achieved, sevalemer 800 mg 3×3 was added with gradually increasing, phosphorus level dropped to 5.2 mg/dl. Genetic analysis revealed GALNT3 homozygous mutation. Genetic counseling and eye examination were recommended. [Figure: see text] CONCLUSION: TC should also be considered in patients with a history of multiple surgery due to soft tissue masses, especially in the presence of hyperphosphatemia. In our case, a mutation was detected at a rather late age, and phosphorus-lowering therapy was started at the age of 38 years and genetic counseling should be offered to these patients at an early age.