Dental manifestations of pseudo-vitamin-D deficiency rickets in a paediatric patient

Abstract

Vitamin D–resistant rickets shows the resistance to vitamin D (Vit-D) therapy, which traditionally works well in cases with deficiency rickets. The signs start appearing as early as in the first month of life and are characterised by the defective mineralisation at the ends of cartilage and bones despite having normal Vit-D levels in the serum. This case report highlights the dental and maxillofacial manifestations in a 3-year-old girl diagnosed with pseudo-Vit-D deficiency rickets. The report also highlights the variations in the dental manifestations of the condition reported in the literature.

Background

Vitamin D–resistant rickets (VDRR) is an inherited disorder characterised by the resistance to vitamin D (Vit-D) therapy, which is considered as a mainstay in the management of rickets. Its signs start appearing in the first month of life and are characterised by the defective mineralisation at the ends of cartilage and bones. Albright et al were the first to document the case of VDRR.¹ VDRR can be broadly classified into hypophosphatemic and pseudodeficiency types. The hypophosphatemic type is characterised by severe hypophosphatemia without the radiological signs of secondary hyperparathyroidism, whereas pseudodeficiency rickets shows hypocalcaemia with bone and musculoskeletal deformities. The former is inherited as an autosomal dominant entity, whereas the later is transmitted as an autosomal recessive trait.^{2 3}

Dental findings in cases with VDRR include dentin defects, unusually large pulp chambers and enlarged pulp horns. Enamel hypoplasia has also been reported in some cases. The other findings include short roots, poorly defined lamina dura and hypoplastic alveolar ridges. These findings are more common in primary dentition than in permanent teeth.^{4 5} Histology of these teeth revealed the presence of large areas of interglobular dentin and calcospherites. The cephalometric studies had revealed deficient anterior cranial base length, ramus height and cranial base angle in these patients.⁶

This case report described the dental and maxillofacial manifestations in a 3-year-old girl diagnosed with VDRR (pseudodeficiency type) along with its differential diagnosis and a summary of variations in the clinical presentation among the cases reported in the literature.

Case presentation

The 3-year-old girl reported to the outpatient department of paediatric and preventive dentistry of a tertiary care hospital with a complaint of mobile teeth. The child was diagnosed with pseudo-Vit-D deficiency rickets and was under treatment at the department of paediatric nephrology. The diagnosis was based on clinical, radiographical and biochemical characteristics observed. There was a history of exfoliation of one of the child’s teeth due to mobility. Thus, anticipating the risk of aspiration of the remaining teeth, the treating physician referred the patient for a dental evaluation.

The child was born through normal delivery and non-consanguineous marriage. There was no history of similar illness among other family members (figure 1). The child’s legs were weak and she was not able to bear her weight. A general examination revealed knee deformity with a broad wrist and protruded chest. The characteristic findings of rickets, that is, pectus carinatum and rachitic rosary, were also evident in the present case. Other findings include sparse hairs, double malleoli and genu vallum with bowed legs (figures 2 and 3). Biochemical features include normal levels of serum phosphorus and calcidiol (25-hydroxy vitamin D) with an elevated serum alkaline phosphatase and low calcium levels (table 1).

Figure 1.

Pedigree chart (created by authors).

Figure 2.

(A) Intraoral photograph with missing tooth 51, alveolar bone loss and marginal gingivitis. (B) Intraoral periapical radiograph with alveolar bone loss and widening of pulp chamber and root canals. (C) Knee deformity with bowing of legs. (D) Broad wrist with widening of the joint (created by authors).

Figure 3.

Extraoral photograph showing frontal bossing and sparse hairs (created by authors).

Table 1.

Biochemical findings of the case at the time of presentation

Investigations	Patient value	Normal range15
Alkaline phosphatase activity (ALP)	1046 U/L	(40–129 U/L)
Ca+	6.9 mg/dL	(8.6–10 mg/dL)
Po4	3.3 mg/dL	(2.5–4.5 mg/dL)
Vit-D3	68.8 ng/mL	Deficient <12 ng/mL Insufficient 12–20 ng/mL Sufficient >20 ng/mL

Created by authors.

The child has a prominent forehead with frontal bossing and deficient midface. Intraoral examination revealed the child had primary dentition with clinically missing tooth 51 (Federation Dentaire International (FDI) notation). Oral hygiene status was poor with generalised chronic marginal gingivitis. Grade III mobility was present with tooth 61, whereas other teeth 52, 62, 71, 72, 81, 82 had grade I mobility which was unseemly for the child’s age.

Investigations

The widening of the wrist and ankle joint and characteristic bowing of the legs with normal Vit-D level and non-response to external Vit-D administration were suggestive of pseudo-Vit-D deficiency rickets (figure 4). An orthopantomogram was done to assess the status of bone, and developing dentition revealed generalised bone loss with the primary teeth and a delay in root development of permanent teeth (figure 5). Intraoral periapical radiograph with maxillary incisors revealed the receded alveolar bone level with enlarged pulp chamber (figure 2).

Figure 4.

(A) Knee radiograph showing metaphyseal splaying and generalised osteopenia. (B) Wrist radiograph with widening of the wrist joint. (C) Radiograph with lower extremity showing deformities with ankle and knee joints with bowing of long bones (created by authors).

Figure 5.

Orthopantomogram showing generalised bone loss, widening of pulp chamber and delayed tooth development (created by authors).

Differential diagnosis

The child reported with the complaint of premature tooth exfoliation and tooth mobility. A generalised alveolar bone loss was also evident on the radiograph. Based on these clinical and radiographical presentations, the following differential diagnosis was made (table 2).^7–12

Table 2.

Conditions with premature tooth loss of primary teeth

Conditions	Aetiology/mode of inheritance	Clinical and radiographical presentation
Localised aggressive periodontitis7	Inflammatory response to bacterias. Local and systemic factor influence the condition. Shows familial pattern, however, exact mode of inheritance is unclear	Localised loss of attachment in primary dentition, most common in molar area with bilateral symmetrical bone loss, premature tooth exfoliation
Papillon-Lefevre syndrome8	Autosomal recessive disorder with mutation in cathepsin C protein	Hyperkeratosis of palms of hands and feet, recurrent sinusitis and/or tonsillitis, aggressive periodontal disease with attachment and bone loss. Precocious loss of dentition
Hypophosphatasia9	Autosomal dominant/recessive mode of inheritance with mutations in the ALPL gene Low level of alkaline phosphatase activity (ALP) for age/sex	Premature loss of primary teeth, enlarged pulp chambers, widening of root canals, shell teeth-like appearance. Skeletal pain, muscle weakness, knock-knees, bowed legs, enlarged joints. Radiographs reveal characteristic radiolucency projecting from growth plates into metaphyses especially in long bones, other features include osteopenia and osteosclerosis
Langerhans cell histiocytosis10	A sporadic, non-hereditary condition due to somatic mutations in the BRAF gene	Red scaly papules in skin folds. Punched-out bone lesion involving skull, long bones. Cough, dyspnoea and solitary lung lesions. Gingival enlargement, ulcerations, mobility of teeth with alveolar expansion, destructive lesion of bone
Leucocyte adhesion deficiency11	Autosomal recessive disorder with immunodeficiencies due to defects in the adhesion of leukocytes (neutrophils) to the blood vessel wall	Recurrent bacterial infection, delayed wound healing, skin abscess Generalised rapid bone loss and inflammation around the teeth
Cyclic neutropenia12	Autosomal dominant disorder with cyclic pattern of recurrent illness due to mutation in gene for neutrophil elastase	Lymphadenopathy, recurrent fever, skin infections, pharyngitis and recurrent cellulitis. Severe gingivitis, mouth ulcers and pronounced alveolar bone loss

Created by authors.

Treatment

The child was under treatment for her systemic condition at the department of nephrology and had shown considerable improvement since then. As per her medical records, Vit-D supplementation was started initially to evaluate the patient’s response to the therapy; however, no improvement was noticed indicating the resistance to therapy. The child had poor oral hygiene along with chronic marginal gingivitis for which oral prophylaxis was done followed by topical fluoride varnish application. Tooth 61 had poor alveolar bone support, and thus considering the risk of aspiration it was extracted under local anaesthesia (2% lignocaine with 1:80 000 epinephrine).

Follow-up

The recall follow-up was planned at every 3-month interval. However, it was difficult to recall the case for clinical examination due to the COVID-19 pandemic. Oral hygiene instructions were reinforced, and the child was assessed for the prognosis of the remaining primary teeth via teleconsultation. There was no further worsening of symptoms pertaining to gingival health and teeth mobility.

Discussion

This case report highlights the dental and maxillofacial findings in pseudo-Vit-D deficiency rickets in a 3-year-old girl. The diagnosis was established based on history, clinical symptoms, radiographical examination and laboratory findings. However, the laboratory findings were of more diagnostic importance considering the common clinical and radiographical presentations seen in the different forms of rickets. Several authors have reported the dental findings in VDRR patients (table 3). The alveolar bone loss with resultant premature exfoliation of teeth and enamel hypoplasia are the most common findings in the majority of reported cases.

Table 3.

Dental manifestations of VDRR described in the literature^16–19

Author/year	Reported cases (n)	Age/gender	Dental findings
Thakur/201916	2	14 years/male 5 years/male	Enamel hypoplasia, dental caries, dentin abnormalities, impacted superneumery teeth, enlarged pulp chambers
Hanna et al/201817	4	6 years 8 months/ male 2 years 6 months/female 3 years 3 months/female 2 years 2 months/male	Premature loss of primary teeth, hypoplastic primary teeth with delayed eruption, congenitally missing permanent teeth, hypoplastic enamel with permanent teeth, enlarged pulp chamber with primary teeth
Hochberg and Weis- man/199518	1	6 years/male	Enamel hypoplasia, severe dental caries, gingivitis, delay in teeth eruption, sinus formation with multiple teeth, absence of lamina dura, enlarged pulp chambers, pulp stone and delay in development of permanent teeth
Liberman et al/198019	1	13 years/female	Oligodontia, enamel hypoplasia resembling amelogenesis imperfecta

Created by authors.

An improvement has been reported in the literature among the cases after administration of calcium, phosphorus and calcitriol, in terms of growth, clinical-radiographical parameters and biochemical abnormalities.¹³ However, this response to the therapies varies with different phenotypes. Hanna et al found that certain phenotype (p.R391S) characterised by thinning of hairs, good response to the treatment and relatively better-anchored teeth compared with other (p.H397P) which shows no loss of hairs, resistance to treatment and premature tooth loss.¹⁴ Tooth development is associated with serum calcium levels during infancy. Thus, when calcium is severely deficient, it results in primary tooth loss. The timings of treatment and the restoration of normal serum calcium levels affect dental health. When the treatment is started on early, lesser number of primary teeth are lost, and tooth structure is affected to a lesser extent. Dental development which is an indicator of the ongoing disease process can be considered as a reflection of the treatment response of the disease overall. However, longitudinal research is still lacking in this regard. The oral manifestations can appear at the onset of the condition. Thus, the dentist’s knowledge about the condition may help to prevent the disease progression via an appropriate referral.

Learning points.

• Pseudo-vitamin-D deficiency rickets is associated with orofacial and dental manifestations, which include frontal bossing, enlarged pulp chambers, periodontal abscess, alveolar bone loss, mobility of teeth with premature exfoliations and diminished lamina dura.

• Early diagnosis and prompt treatment of the systemic condition may help to arrest the progressive bone loss and associated premature teeth exfoliation.

• The dentists should be aware of the manifestations of the condition. Thus, aid in diagnosis and be part of an interdisciplinary team for its comprehensive management.

Ethics statements

Patient consent for publication

Consent obtained from parent(s)/guardian(s).