Abstract
Introduction:
Renal phosphate-wasting disorders are the most common form of hereditary rickets and osteomalacia in western countries, but are rarely reported in India. Therefore, we report here a case of hypophosphatemic rickets.
Aim and objective:
To report a case of hypophosphatemic rickets presenting with recurrent pathological fractures.
Material and Methods:
A 34-year-old premenopausal lady presented with recurrent pathological fractures, bone pain, and muscle weakness since 14 years of age. A thorough history was taken followed by clinical examination, and relevant biochemical and radiological investigations were done.
Results:
Height was 125 cm, arm span 145 cm, body weight 30 kg, and body mass index (BMI) 19.2 kg/m2. Dental caries, kyphoscoliosis, shortening of left lower limb, bilateral coxa vara deformity of knee, muscle weakness, and bone tenderness were present. Calcium was 9.4 mg/dL, phosphorus: 1.8 mg/dL, albumin: 4.0 gm/dL, alkaline phosphatase: 360 U/L, creatinine: 0.4 mg/dL, a normal ammonium chloride (NH4Cl) loading test,24-hour urine calcium excretion: 102 mg/day, 25-hydroxyvitamin D3 [25(OH)D3]: 21.6 ng/mL, intact parathyroid hormone (PTH): 43.74 pg/mL, fraction excretion of phosphate (PO4): 40%, tubular maximum reabsorption of phosphate per unit of glomerular filtrate (TmP/GFR): 0.65 mg/dL, and fibroblast growth factor (FGF)23: 321.4 RU/mL. Skeletal X-rays showed multiple old fractures and pseudofractures. Magnetic resonance imaging (MRI) of the whole body showed no evidence of tumor. Fludeoxyglucose (18F)-positron emission tomography (FDG-PET) computed tomography (CT) scan revealed metabolically active marrow with multiple areas of fracture and FDG-avid lesions in both lungs but no CT-based findings.
Conclusion:
Hypophosphatemic rickets or osteomalacia, possibly hereditary, is a rare cause of recurrent pathological fractures.
Keywords: Hypophosphatemic rickets, osteomalacia, pathological fracture
INTRODUCTION
Nutritional deficiency is no longer an important cause of rickets in the western world, although it still is in India.[1] Rickets and osteomalacia can occur in association with a variety of disorders of proximal renal tubular function; these disorders have, in common, increased renal clearance of inorganic phosphates and hypophosphatemia with a normal glomerular filtration rate (GFR). Primary hypophosphatemic rickets is characterized by a severely short stature and rickets in association with hypophosphatemia and hyperphosphaturia and usually has an X-linked mode of inheritance.[2] In this report, we describe a female with hypophosphatemic rickets, possibly autosomal dominant.
CASE REPORT
A 34-year–old premenopausal unmarried lady, born out of nonconsanguineous marriage presented with recurrent pathological fractures, bone pain, and muscle weakness since 14 years of age. Since 14 years of age she sustained multiple fractures of her upper and lower extremities following trivial trauma and became homebound. There was no suggestion of any chronic systemic disease. Family history was insignificant. Examination revealed a well-nourished lady with height 125 cm (<3rd percentile), weight 30 kg (3rd percentile) and a body mass index (BMI) of 19.2 kg/m2. Upper segment to lower segment ratio was 1.2. She had dental caries, kyphoscoliosis, shortening of left lower limb, bilateral coxa vara deformity of knee, muscle weakness, and bone tenderness. X-rays showed multiple old fractures and pseudofractures [Figures 1a and b]. Biochemical investigations revealed total calcium: 9.4 mg/dL, phosphorus: 1.8 mg/dL, albumin: 4.0 g/dL, alkaline phosphatase: 360 U/L, creatinine: 0.4 mg/dL, a normal ammonium chloride (NH4Cl) loading test, 24-hour urinary calcium excretion: 102 mg/day, 25-hydroxyvitamin D3 [25(OH)D3]: 21.6 ng/mL, intact parathyroid hormone (PTH): 43.74 pg/mL, fraction excretion of phosphorus: 40%, tubular maximum reabsorption of phosphate per unit of GFR (TmP/GFR): 0.65 mg/dL, fibroblast growth factor (FGF)23: 321.4 RU/mL [Table 1]. Magnetic resonance imaging (MRI) of the whole body showed no evidence of tumor. Fludeoxyglucose (18F)-positron emission tomography (FDG-PET) computed tomography (CT) scan showed metabolically active marrow with multiple areas of fracture, FDG-avid lesions in both lungs but no CT-based findings [Figure 2].
Figure 1.
(a and b) X ray showing multiple old fractures and pseudofractures
Table 1.
Biochemical investigations
Figure 2.
Fluorodeoxy glucose – positron emission tomography (FDGPET) computed tomography (CT) showing metabolically active marrow with multiple areas of fractures, FDG avid lesions in both lungs but no CT based findings
DISCUSSION
In India, malnutrition continues to be the leading cause of rickets, although other causes of rickets are being increasingly recognized.[3] In this case report, we describe a female patient who had advanced changes of rickets/osteomalacia. Historically, no other family members were affected. Our patient might be a case of hereditary hypophosphatemic rickets, possibly autosomal dominant. In developed nations, nutritional rickets, primarily due to deficiency of vitamin D, has almost been eliminated as a result of fortification of some foods. By the 1940s, deficiency of vitamin D was no longer considered to be an important cause of osteomalacia and rickets. In North America, the most common form of inherited rickets is X-linked dominant hypophosphatemic rickets.[4] This entity was first described by Albright and co-workers in 1937.[5] The phenotypic trait of hypophosphatemia is transmitted on the X-chromosome. Patients with familial hypophosphatemic rickets are recognized by marked rickets with hypophosphatemia and hyperphosphaturia coupled with increased serum alkaline phosphatase with normal or slightly reduced serum calcium; excretion of urinary phosphate is high, despite hypophosphatemia indicating a defect in renal tubular reabsorption of phosphate. Phosphaturia is unassociated with aminoaciduria, glucosuria, bicarbonaturia, or kaliuria. Serum levels of immunoreactive parathyroid hormone are either normal or mildly increased. Serum levels of 25(OH)D are normal, whereas levels of 1,25-dihydroxyvitamin D are either normal or low. Our case had insufficiency of 25(OH)D. The only logical explanation for this biochemical abnormality could be a concomitant deficiency of vitamin D.
CONCLUSION
Hypophosphatemic rickets or osteomalacia is a rare cause of recurrent pathological fractures.
Footnotes
Source of Support: Nil
Conflict of Interest: None
REFERENCES
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