|Year : 2010 | Volume
| Issue : 4 | Page : 302-306
Familial hypophosphatemic rickets
A Sattur, VG Naikmasur, R Shrivastava, M Babshet
Department of Oral Medicine and Radiology, SDM College of Dental Sciences and Hospital, Dharwar, Karnataka, India
|Date of Web Publication||25-Jan-2011|
Department of Oral Medicine and Radiology, SDM College of Dental Sciences and Hospital, Dharwar - 580 009, Karnataka
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Rickets is the failure of mineralization of osteoid and newly formed bones in a child skeleton. It is commonly associated with vitamin D deficiency; however, it can be because of a decrease in the serum phosphate levels leading to inadequate mineralization of cartilage and bone, consequent skeletal deformities, and growth retardation. The hypophosphatemic conditions that interfere in bone mineralization comprise many hereditary or acquired diseases. One of the hereditary types of hypophosphatemic rickets is the familial hypophosphatemic rickets. This rare variety was diagnosed in a 9-year-old patient who had come with a chief complaint of a missing tooth. In the present case, radiographic aspects of oral and systemic manifestations of familial hypophosphatemic rickets are highlighted.
Keywords: Cemental dysgenesis, familial rickets, hypophosphatemia
|How to cite this article:|
Sattur A, Naikmasur V G, Shrivastava R, Babshet M. Familial hypophosphatemic rickets. J Indian Soc Pedod Prev Dent 2010;28:302-6
| Introduction|| |
The vitamin D-resistant rickets was first documented by Albright et al., as early as in the 19th century itself. The pathophysiologic mechanism shared by them is the reduction in the phosphate reabsorption by renal tubuli which leads to hyperphosphaturia and hypophosphatemia, causing rickets. X-linked hypophosphatemic rickets (XLHR) is a familial syndrome characterized by the inadequate mineralization of cartilage and bone, consequent skeletal deformities, and growth retardation. The present case report shows the clinical, radiological, and pathological evaluation of familial hypophosphatemic rickets in a 9-year-old boy who came with the chief complaint of pain and missing tooth.
| Case Report|| |
A 9-year-old boy visited our hospital with the chief complaint of pain in the lower front region since 3 years and a missing tooth in the upper front region of the jaw since 1 year. The pain was mild and intermittent with occasional pus discharge. There was no eruption of the permanent tooth after the shedding of the deciduous tooth in the second quadrant of the jaw since 1 year. As per the parents' observations, the child had difficulty in walking since he was 3 years old and also bowing was observed in the extremities since 1 year. We could observe that the mother also had a limping gait and short stature. On further investigation, the mother revealed that she had undergone surgery for bow-leg deformity and multiple root canal treatments. The child has two elder sisters who are apparently normal and there was no contributing paternal history.
General physical examination revealed that the height and weight were 114 cm and 18 kg, respectively, which are less as compared to the average height and weight of an age-matched Indian boy. The patient had a dolicocephalic face, frontal bossing, and incompetent lips [[Figure 1]a]. There was bowing of the arms and legs with enlargement at the wrist and the ankle joints [[Figure 1]b and c]. The presence of rachitic rosary, Harrison's groove, and lumbar lordosis was also noted. On intraoral examination, mixed dentition was present with the missing maxillary permanent left central incisor, grade II mobile mandibular deciduous left first molar, and mandibular deciduous right lateral incisor and decayed maxillary permanent right first molar and maxillary permanent left first molar, with fair oral hygiene [Figure 2]. Considering the familial history and the clinical features favoring rickets, the provisional diagnosis of familial rickets was made.
|Figure 1 :(a) Dolicocephalic face, frontal bossing, and incompetent lips. (b and c) Bowing of the arms and legs marked with bold arrows and with the enlargement at the wrist and the ankle joints marked with broken arrows|
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The OPG showed decreased a cortical bone density in both the maxilla and mandible with thinning of the inferior cortical border of the mandible. Both primary and permanent teeth showed taurodontism with a generalized diminished lamina dura [Figure 3]. IOPA radiographs showed generalized taurodontism, reduced density of the enamel and dentine [Figure 4]. Frontal and lateral skull radiographs showed the presence of diffuse copper beaten appearance with premature closure of sutures [Figure 5] and [Figure 6]. The hand and wrist AP radiograph showed diffuse osteopenia in the form of coarse medullary trabeculae and endosteal resorption. The distal end of the radius and ulna showed metaphyseal splaying with widening of growth plates [[Figure 7]a]. A similar finding was observed bilaterally on the distal end of the femori proximal and distal metaphysis of the tibia and fibula [[Figure 7]b]. The femur showed the coxavara type of deformity [[Figure 7]c]. The chest radiograph revealed mild splaying of cartilaginous ends of ribs [[Figure 7]d]. All long bones showed bowing deformity. Sonography of kidneys was advised to rule out nephrocalcinosis, which came negative.
|Figure 3 :Orthopantomograph shows a decreased cortical bone density with thinning of the inferior cortical border of the mandible (broken arrow). Both primary and permanent teeth show taurodontism with a generalized diminished lamina dura (bold arrow)|
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|Figure 4 :Full mouth radiographic survey reveals enlarged pulp chambers of all teeth with a reduced density of the enamel and dentine|
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|Figure 5 :Posterior-anterior skull radiograph shows a diffuse copper beaten appearance with premature closure of sutures|
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|Figure 6 :Lateral skull radiograph shows a diffuse copper-beaten appearance with premature closure of sutures|
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|Figure 7 :Diffuse osteopenia of long bones. The broken arrows (a, b, and d) show metaphyseal splaying. The bold arrows (b and c) show bowing deformity of the tibia and femur, respectively. The curved arrow (c) shows the coxavara deformity of the femur|
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One of the deciduous teeth was subjected to ground sectioning which revealed a large pulp chamber and numerous areas of interglobular dentine throughout the thickness of the dentine. The cementum was absent in the apical third, while only a thin layer was present in the cervical and middle third portion of the root. Observing these dental and skeletal findings, blood investigations were advised. The blood report revealed decreased serum phosphate, 2.6 mg/dL (normal range = 3.7-5.6 mg/dL), and elevated serum alkaline phosphatase, 514 IU/L (normal range = 150-380 IU/L); however, serum calcium was within the normal range, 8.5 mg/dL (normal range = 9-11 mg/dL). The decreased levels of serum phosphate show decreased absorption or increased renal wasting of phosphate, while the elevated serum alkaline phosphatase levels suggest an increased bone turnover. From the above history, clinical examination, and the investigations, we arrived at a final diagnosis of familial hypophosphatemic rickets.
Initially, the dental management was done with oral prophylaxis, the restoration of decayed and the extraction of the mobile teeth. A neutral phosphate syrup, 15 ml, was prescribed with three divided doses daily for hypophosphatemia; also, vitamin D 0.25 ΅g was supplemented in once daily dose. The patient was subjected to physical therapy like cycling and exercise. On 6-month follow-up, the patient showed improvement in gait and physical activity.
| Discussion|| |
Rickets is the failure of mineralization of osteoid and newly formed bones in a child. The term is derived from an old English word "wrickken," which means "to twist" and a Greek word "rachitis," which means inflammation of the spine. When the demineralized osteoid accumulates at the sites of bone formation, bones gradually soften leading to deformities in association with weight-bearing sites. This clinical entity in England was termed as English disease in the 17 th century by Francis Glisson. Later in the mid-17 th century it was termed as rickets by Park and Hunter.  By the end of the 19th century, the near endemic nature of rickets among children under the blackened skies of industrial cities in Europe was widely recognized.  It was in the 20th century when vitamin D was discovered and used for therapeutic purpose. 
Initially, environmentally caused rickets was very common; however, when it was treated and prevented by public health measures, the vitamin-D-resistant rickets came into picture. Albright et al. highlighted that some of the patients with rickets did not respond to physiological doses of vitamin D and named the condition as vitamin-D-resistant rickets. Later studies showed that treatment of rickets was possible by vitamin D in doses higher than its physiological doses and eventually termed it as vitamin D refractory rickets. Fraser and Salter studied 13 cases of hereditary vitamin D refractory rickets. The hereditary forms were further divided into familial hypophosphatemia rickets and vitamin D dependency. The latter is caused by the deficiency of an enzyme 25-hydroxyvitamin D-1a-hydroxylase which is responsible for the synthesis of 1,25 dihydroxycholecalciferol. This substance specifically acts on the intestine to stimulate calcium transport. Therefore, the biosynthesis impairment of the vitamin D hormone causes calcium deficiency manifesting with signs of hypocalcemia and in later stages with hyperparathyroidism. Vitamin D dependency shows an autosomal recessive pattern.
The familial hypophosphatemic rickets is caused by a renal tubular phosphate-wasting disorder. It shows an X-linked dominant pattern affecting males uniformly and females variably. It has an incidence of 1:20,000.  The renal tubular rejection of phosphate in XLHR causes decreased serum phosphate levels. XLHR resulting from inactivating mutations in an endopeptidase termed PHEX (phosphate-regulating gene with homologies to endopeptidase on the X- chromosome).  A substrate for PHEX has not yet been identified and hence its role in pathophysiology in hypophosphatemia is not clear. Certain studies have shown that PHEX is highly expressed in bone and in teeth.  Since the substrate of PHEX is not yet known, it is not possible to say how the loss of function of PHEX causes these bone and teeth defects and renal phosphate leak. 
Clinical features include decreased vertical height, craniotobes, rachitic rosary, bowing leg deformity (genu varum) or knock knee (genu valgum), double malleoli sign of ankles, metaphyseal hyperplasia of wrist, and Harrison's groove on the chest.
In a conventional radiograph, rickets usually presents with widening of the physis with cupped and splayed metaphysis. The skull shows frontal bossing, premature fusion of the sagital suture leading to copper beaten appearance, and postural molding:
1. Axial skeleton shows the following:
- Costochondral junction shows cupping and splaying of rib ends.
- Spine shows scoliosis or lordosis and biconcave vertebral bodies.
- Pelvis shows triradiate appearance due to the inward migration of the sacrum and acetabula.
2. Appendicular skeleton shows the following:
- Ossification centers of the epiphyses show an indistinct outline.
Diaphysis shows osteopenia, subperiosteal lucent lines tunneling, and bowing. Bowing deformity is common in the femur and tibia. The femur shows the coxavara type of deformity, wherein the neck makes an angle of less than 120° with the shaft of the femur.
The oral finding of XLHR is the presence of multiple dental abscesses in both the dentitions,  in the absence of obvious cause such as caries or trauma involving pulp.  Radiographs reveal enlarged pulp chambers with pulp horns that extend to enamelodentinal junctions.  The occurrence of the periapical lesions or gingival abscesses without any obvious cause is explained in general by the penetration of microorganisms through dentinal clefts, tubular defects, or voids in the calcified metrics of the dentine.  The concentration of calcium and phosphorous along with the calcium to phosphate ratio of the enamel in hypophosphatemic rickets are nearly equal to those of normal teeth, although the degreeof radiodensity is less in hypophosphatemic rickets.  The concentration of phosphate in the dentine is extremely low.  The microradiograph of teeth in hypophosphatemic rickets showed extensive areas of the circumpulpal dentine consisting of radiopaque calcospherites separated by multiple irregular radiolucent zones of the interglobular dentine.  The early exfoliation of deciduous teeth in rickets can be attributed to poorly defined lamina dura, dysplastic roots, and hypoplastic alveolar ridge. 
The treatment of hypophosphatemic rickets is done by the oral administration of phosphorus, 1-4 g daily in five divided doses. The objective of the treatment is to raise the serum phosphate to about 4 mg/dL. Treatment of hypophosphatemic rickets with orthophosphate in doses sufficient to restore the serum phosphate to normal results in radiographically evident healing of rickets and promotes "catch-up" linear growth in childhood.  Phosphate loading decreases the level of ionized calcium in serum and causes the serum concentration of iPTH to increase. Vitamin D is used as an adjuvant to phosphate therapy to avoid this complication. The dose of vitamin D ranges from 0.1 to 1.2 mg per day depending on the amount of phosphate administered and the patients' particular need for vitamin D. 
| Conclusion|| |
Being dentists we hardly come across this rare variety of rickets in our clinics. However, with thorough case history, systematic clinical examination, and appropriate investigations, it is possible to diagnose even rare diseases. In this case, though the patient presented with pain and missing tooth, we were able to diagnose familial hypophosphatemic rickets and treat the patient at its earliest.
| References|| |
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
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