Oral findings of hypophosphatemic vitamin D-resistant rickets: report of two cases

Hypophosphatemic vitamin D-resistant rickets or X-linked hypophosphatemia (XLH) is a rare hereditary metabolic disease manifesting marked hypo-phosphatemia, short stature and rickets. Its prevalence is approximately 1 in 20 000. Except early exfoliation of the teeth, there are a few oral findings of XLH described in China.1,2 Here we present two cases in one family. CASE REPORT Case 1 A 3 years and 1 month old Chinese girl visited our hospital because of her two incisors exfoliation for 6 months, bowed legs deformity and growth retardation for 1 year. The patient was the first offspring of the parents after a full term gestation and measured 3500 g in weight and 49 cm in length at birth. She started to talk at 1 year old and walk at 1 year and 6 months old. Her bowed legs, staggering gait and developmental retardation were found at age 2, and the supplementation of vitamin D and calcium could not improve these symptoms. The first primary tooth erupted at 4 months old, and all primary teeth erupted at age 2. At 2 years and 6 months old, two maxillary central incisors exfoliated one after the other. The exfoliated teeth were intact, caries-free and had no history of trauma. Her mother also had XLH together with bowed legs, short stature and toothache. However neither paternal nor maternal relatives showed any signs of XLH (Fig. 1).Fig. 1.: Pedigree chart showing the transmission of rickets from the maternal side. The arrow indicating the proband.The patient's height and weight were 80.8 cm and 12.0 kg, which were -4SD and -2SD from the height and weight averages of age-matched Chinese girls, respectively. General physical examination revealed marked genu varum, bowlegs and epiphyseal enlargement at the wrists and ankles. The distance of two knee joints was 10 cm. Oral examination revealed the primary dentition was present. A good oral hygiene with normal teeth and gingival color and shape existed. For all these teeth, no periodontal pocket was detected and no caries was found. The maxillary central incisors (51, 61) were missed. Many teeth were loose. The teeth mobility of the maxillary lateral incisors (52, 62), the mandibular central and lateral incisors (71, 72, 81, 82) was II degree and that of the left maxillary canine (63), the left mandibular canine and second molar (83, 85) was I degree (Fig. 2).Fig. 2.: Oral examination showing two maxillary central incisors (51, 61) missed, good oral hygiene and caries free primary teeth of patient 1.The laboratory examination showed an elevated alkaline phosphate level at 811 U/L (normal range, 15–350 U/L) and hypophosphatemia at 0.53 mmol/L (normal range, 1.45–2.10 mmol/L) and blood calcium at 2.45 mmol/L (normal range, 2.00–2.80 mmol/L). Moreover, measure-ment of urinary phosphate excretion indicated a lower phosphate re-absorption rate of 68.9% (normal range, 84.7%97.9%). Rachitic changes at epiphyses of the radius, ulna, tibia and fibula were showed by radiographic examination. Panoramic radiographic film showed enlarged pulp chambers, radicular canals and open apices in all primary teeth. Large mesial pulp horns were noted in all second primary molars, and the horns extended to the dentino-enamel junction. The short roots were observed in mandibular incisors. Panoramic radiograph also showed evidence of generalized bony rarefaction with absence of lamina dura around the roots of erupted primary teeth and absence of bony crypts around forming permanent teeth. A hypoplastic alveolar ridge was also observed (Fig. 3).Fig. 3.: Panoramic radiograph of patient 1 showing noted large pulp charmers, radicular canals and open apies in all primary teeth; large mesial pulp horns in second primary molars; absence of lamina dura around the roots of primary teeth; absence of bony crypts around forming permanent teeth.Together with all the clinical, radiographic and laboratory findings, the patient was diagnosed as hypophospatemic rickets and was administered neutral phosphate and 1,25-dihydroxy vitamin D. We performed topical fluoride varnishes to the anterior primary teeth and fit and fissure sealants to the primary molars. Case 2 The patient was the mother of patient 1. She was 28 years old. The patient's height and weight were 129 cm and 49.5 kg respectively. She had marked bowlegs and the distance of two knee joints was 40 cm. She started to suffer from dental abscess in non-carious teeth at age 8. Laboratory examination showed an elevated alkaline phosphate level at 167 U/L (normal range, 30–150 U/L), hypophosphatamia at 0.75 mmol/L (normal range, 1.45–2.10 mmol/L) and blood calcium at 2.35 mmol/L (normal range, 2.00–2.80 mmol/L). Oral examination revealed absence of majority of the teeth except for 13, 12, 23, 26, 27, 35, 36 that were all loose. Their mobility was from II to III degree. An abscess was found at the labial periapical region of the right maxillary lateral incisor, along with a negative response to pulp vitality testing. However, no clinically detectable changes such as caries, tooth fractures, or periodontal pockets that could induce necrosis were found (Fig. 4).Fig. 4.: Oral photograph of patient 2 showing dental abscess at the labial periapical region of the right maxillary lateral incisor (arrow).Radiographically, enlargement of pulp chambers were observed in the maxillary canines, the first and second left maxillary molars and the first right mandibular molar. The periapical radiolucencies were found on the right maxillary lateral incisor and maxillary canines. The alveolar bone around the maxillary and mandibular molars was absorbed horizontally (Fig. 5).Fig. 5.: Panoramic radiograph of patient 2 showing periapical radiolucencies of the right maxillary lateral incisor and maxillary canines; horizontal absorption of alveolar bone.DISCUSSION XLH, firstly reported by Albright et al in 1937, is a syndrome showing marked hypophosphatemia, short stature and rickets. XLH is associated with defective re-absorption of phosphate in the proximal renal tubule and inadequate synthesis of 1, 25-dihydroxy vitamin D from its precursor 25-hydroxy vitamin D. Most patients with XLH appear in a familial line of X-linked dominant inheritance with the same prevalence in both sexes. However, it may also occur sporadically.3 Since the early case reports of XLH, a specific dental finding of abscess formation in clinically normal teeth has been described in most cases.4 The dental abscess can be detected in both primary and permanent dentitions.5 Case 2 supported their findings that there were multiple non-carious abscessed permanent teeth. Her panoramic radiograph showed periapical radiolucencies in the right maxillary lateral incisor. So we speculated that the dental abscess was caused by bacterial invasion into the pulp tissue by way of a microscopic cleavage of the enamel and dentin.4 Histological findings of the teeth in XLH include enlarged pulp chambers, wide predentin, marked globular dentin, and tubular dentinal defects extending from the pulp to the enamel. Enamel hypoplasia may or may not be present. The calcification process of the dentin was impaired because of hypophosphatemia. The incompletely mineralized dentin exists in the form of calcospherites, which trap microorganisms and also impede mechanical endodontic cleaning.5 Usually the younger the patient is when the first abscess appears, the more severe the dental manifestation becomes.6 The first dental abscess of patient 2 appeared at age 8 and she never accepted neutral phosphate and dental treatment, so most of her teeth exfoliated. This is common in China.1,2 Because primary enamel and dentin formation occur between 4 months in utero and 11 months after birth, the defects in the primary dentition usually can not be prevented.5 In case 1, the enlarged pulp chambers, high pulp horns extending to the dentino-enamel junction, dysplasia root, poorly defined lamina dura, hypoplastic alveolar ridge and absence of bony crypts around forming permanent teeth were observed. The clinical findings (such as dental caries and tooth trauma) were not detected and so the dysplasia root, poorly defined lamina dura and a hypoplastic alveolar ridge may be responsible for the maxillary incisors early exfoliation and other teeth being loose.7 For the patients with XLH, the dentition is highly susceptible to dental caries and attrition, and bacteria can invade easily from oral cavity to dental pulp by way of structural defects in enamel and dentin, resulting in pulpitis.8 Therefore, to prevent multiple dental abscesses, both early treatment and preventive care for caries and attrition are necessary.9 For the patients with XLH, professional dental care consisting of periodic examinations, topical fluoride applications and maintenance of good oral hygiene is imperative. Pit and fissure sealants are useful when the teeth are erupting as they prevent ingress of bacteria into the enamel microfractures as well as initiation of caries in the deep pits and fissures. In case 1, although she had no dental abscess and had good oral hygiene, we applied sealants to her caries-free molars and topical fluoride varnishes to her anterior teeth to prevent pulpitis and dental abscess. In summary, the dental abscess in clinically normal teeth, the early spontaneous exfoliation of clinically intact primary teeth and the numerous teeth missing were the characteristics of our patients with XLH. The numerous teeth missing may be related to the lack of the knowledge of the dental findings with XLH and early treatment and preventive care were not performed as soon as possible. So dentists are advised to provide information about the dental characteristics of XLH to pediatrician who might first diagnose such patients and who might request referrals to dentists as early as possible to prevent potential, subsequent serious dental infections. Acknowledgement: The authors thank Dr. RUAN Wen-hua for his proofreading this manuscript.