Global microarray was performed from Trans-Iliac Bone biopsy from the patient with clinically characterized Fibrogensis imperfecta ossium (FIO). A 40-year-old male patient with clinically characterized Fibrogensis imperfecta ossium (FIO) includes fragility fracture with osteomalacia (Losser’s zone). On examination, his height was 158 cm, weight 47 kg, body mass index (BMI) 16.5, and his blood pressure was 120/80 mmHg. He had no palpable goiter, neck masses or lymphadenopathy. He had no exostosis or bony deformity. He had difficulty in getting up from squatting position and needed a stick to help with walking. The hip joint movements were painful and restricted.. The rest of the examination including abdomen was other wise normal or non-contributory. His laboratory evaluation was as follows: hemoglobin 13.2gm/dl, total WBC 7200/mm3 and erythrocyte sedimentation rate12 mm for 1st hour. Mean ± SD (3 values) serum calcium (Ca) adjusted for albumin was 9.5 ± 1.3 mg/dl (reference range: 8.5 - 11mg/dl). Serum phosphate (PO4) was 3.5 ± 0.3 mg/dl (reference range 3.5-5.0 mg/dl), serum magnesium 1.6mg/dl (reference range 1.58-2.55 mg/dl), total alkaline phosphatase (AP) 39.6 ± 2.6 KA Units (reference range: 3 – 13 KA Units), serum creatinine (Cr) was 1.1 mg/dl. Liver function tests were normal. Twenty four hour mean urine Ca, and phosphorus was 65.3 and 563 mg/d, respectively. The renal tubular handling of phosphate was normal (TmP/GFR 4.2 mg/dl – normal 2.4-4.2). The serum intact parathyroid hormone (iPTH) level by immunochemilunometry was 19 pg/ml (reference range: 10-69 pg/ml).Serum 25-hydroxyvitamin D level was 59.9( reference range 9 – 37 ng/ml). Serum 1,25-hydroxyvitamin D level was 76.6 ng/ml (reference range – 3 ng/ml). Arterial blood gases and urine pH were within normal range. Thyroid function tests were normal. Serum tissue transglutaminase antibody (tTG) titre was negative. Urine for Bence Jones protein was negative and serum electrophoresis was normal. Radiographs of the skull and hands were normal. The lumbar spine showed “rugger –jersey” spine with osteopenia . Views of the pelvis showed bilateral coxa vera and bilateral femur neck fracture with “fishnet appearance”. The chest radiograph showed multiple Looser zones with fractures of several ribs. The lower end of tibia showed “fishnet appearance”, tendon calcification and new bone formation. Ultrasonography of the neck did not reveal any abnormality in the thyroid or parathyroid glands. Ultrasonography of the abdomen and KUB region was normal. A 99mTc sestamibi scan was normal. Bone mineral density (BMD) of the hip with a T-score of -2.2 SD. Magnetic resonance imaging of pelvis showed fracture of bilateral neck and hypointense marrow on T1W and T2W sequences . A 99mTc MDP bone scan showed increased radiotracer uptake bilaterally in the shoulders, elbows, wrists, small joints of hands, multiple sites at bilateral ribs, the entire vertebral column, and lower end of tibia but not the skull (beheaed scan). Transiliac bone biopsy showed thickened bony trabeculae with obliteration of marrow spaces and at places, focal areas of exaggerated osteoclastic activity. There was prominent osteoblastic proliferation as well as osteoid like areas were also seen. At places it showed sclerosis, eaten up edges of bone and foci of new calcification (bone formation). With the above mentioned clinical and investigation proile a diagnosis of FIO was considered most likely
FIO may easily be misdiagnosed because of its superficial similarity to axial osteomalacia osteoporosis, and other metabolic bone disorders with pathological fractures. Bone pain or pathological fractures in a previously healthy adult should lead to radiological and biochemical investigation. Generalized increase in radiological bone density may indicate myelofibrosis or fluorosis but an increased level of alkaline phosphatase favours Paget’s disease or osteomalacia. Bone biopsy suggests gross osteomalacia until the nostic process is rarely logical, but it would not be so delayed if bone sections were always examined under polarized light. There are many unsolved problems in this crippling condition. Apart from complete ignorance of the cause, yet it is not known, what is replacing the mature collagen of bone, why other collagen-containing tissues are apparently unaffected. Why patients commonly have circulating paraprotein and whether there is any effective treatment. Till date, there is no literature has been reported exploring the genes involved in the pathogenesis of FIO. Hence, aim of present study is identification of various genes involved in the regulation of various signaling pathways involved in pathogenesis of FIO.
Overall design: Total RNA was isolated from Trans-Iliac Bone biopsy (Control Individual (n=1) & Patient (n=1)) using TRIZOL method and global microarray was performed on Affymetrix Genechip HumanPrimview platform. The array was performed on duplicate.
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