Hypophosphatemia or hypophosphatemic rickets is an abnormality of renal tubular transport of phosphate that can present in various forms. These include X-linked (OMIM #307800), the autosomal dominant vitamin D-resistant forms (OMIM #193100), and the autosomal recessive inherited trait (OMIM #241520) [3, 21]. Clinical features often become evident by the second year of life and include short stature and boxed legs [3, 21].

Dentally these children have thin hypomineralized enamel along with large pulp chambers and high pulp horns which can result in pulp exposures even in the absence of dental caries. These pulp exposures can lead to spontaneous dental abscesses that result in bone loss and the early loss of primary teeth [3, 21].

Diagnosis will often be made by a physician prior to any dental examination. However, dental radiographs will indicate the enamel and pulp chamber changes already mentioned. In addition, changes in the trabeculation of the alveolar bone along with abnormal or absent lamina dura can be observed radiographically [3].

Treatment will depend upon the patient’s presentation. Patients will often be given vitamin D analogs and phosphate supplements to improve tooth and bone mineralization. Pulp therapy followed by full-coverage crowns is often indicated along with extraction of abscessed teeth. Despite these different interventions and treatment, dental management in patients with severe dental manifestations is challenging, and outcomes of these therapeutic approaches are not well documented.

Hyperthyroidism (OMIM #275000) is an autosomal dominant condition that results in an autoimmune reaction. Antibodies to the thyrotropin receptors are generated which results in an overproduction of thyroid hormone via a physiological feedback cycle. In the presence of preexisting periodontal bone loss, an increase in circulating thyroid hormone will result in an increase in the number of bone resorbing cells which in turn results in an increase in bone maturation and turnover. This accounts for the alveolar bone loss, premature exfoliation of the primary dentition, and an associated accelerated eruption of the permanent dentition [1, 22].

This increase in circulating thyroid hormone is also the etiological factor for the clinical features seen in hyperthyroidism. These include hyperactivity and emotional disturbances [1, 22]. Diagnosis would be based on blood work which would show an increased level of circulating thyroid hormone, and dental treatment would be based on the patient’s symptoms.

Hypophosphatasia is characterized by improper mineralization of bone secondary to defective or deficient alkaline phosphatase [1, 3, 15, 23]. This inheritable condition has multiple forms with different modes of inheritance including autosomal recessive and autosomal dominant transmission [1, 3, 24].

Although the three different forms of hypophosphatasia vary in prognosis, in general the earlier the disease manifests itself, the increased severity of the disease [1, 3]. The phenotypes for these forms vary from the mildest with premature loss of deciduous teeth to severe abnormalities of bone with neonatal death [15].

The three forms, which are based on age of onset, are infantile, juvenile or childhood, and adult [3, 25]. These three types of hypophosphatasia have historically been delineated based on the time of diagnosis and level of severity [3]:

The predominant dental finding in hypophosphatasia is mobility and premature loss of the primary teeth, most often the mandibular anterior [3, 25]. This tooth loss is usually spontaneous with the exfoliation being associated with a loss of alveolar bone along with defective or hypoplastic cementum (Fig. 3.4) [1, 3]. Alkaline phosphatase is critical for normal development of mineralized tissues, and hypophosphatasia results in abnormal cementoblast function and the cell’s ability to regulate pyrophosphates critical for normal tissue formation and mineralization during cementogenesis. This defective cementum results in a weakened tooth to alveolar bone attachment which in turn leads to the loss of the primary dentition [15]. This tooth loss is associated with minimal gingival inflammation and minimal plaque buildup (Fig. 3.5) [1, 14].

Since the teeth are usually affected in the order that they are formed, teeth that are formed earlier are the teeth that are usually involved; this includes the mandibular anterior primary teeth [15]. It should be noted that posterior teeth can also exfoliate prematurely [23]. Additional dental findings that have been reported include enamel hypoplasia, enlarged pulp chambers and root canals, bulbous crowns, and delayed dentin formation [23, 24].

Hypophosphatasia can be diagnosed in two different ways. Laboratory tests can be used to determine the level of serum alkaline phosphatase. In hypophosphatasia a deficient serum and bone alkaline phosphatase activity is found [3, 15, 23]. An additional method of diagnosis involves histological examination of the cementum. Histological samples will indicate hypoplasia of the cementum to the point of a virtual absence of it, resulting in exfoliation of the primary dentition prior to root resorption [1, 23].

Recently, Whyte et al. [26] reported the results of a multinational, open-label study of treatment with ENB0040, a recombinant human tissue nonspecific alkaline phosphatase (TNSALP; 171760) coupled to a deca-aspartate motif for targeting, an enzyme replacement therapy for infantile hypophosphatasia. In this study 11 infants or young children with life-threatening hypophosphatasia were enrolled. Improvement in developmental milestones and pulmonary function along with the healing of bony changes was noted in nine patients after 6 months of therapy [26]. Management of this condition has until now been palliative in nature, aimed at the relief of symptoms often by the use of nonsteroidal anti-inflammatory medications [15, 23]. Dental management emphasizes thorough prevention and oral hygiene regimens [23]. Although the prognosis for the affected primary teeth is poor, it is good for the permanent teeth as these are usually uninvolved [23]. It is not yet clear what the potential benefit of enzyme replacement therapy might be for the dental manifestations and timing of treatment may be problematic unless therapy is initiated during root formation so cementogenesis can progress normally.

With an onset by 4 years of age, prepubertal periodontitis exists in both localized and generalized forms [1]. The localized form presents with little gingival involvement, demonstrating few signs of inflammation [1]. In the generalized form, severe acute gingival inflammation and recession are noted around all of the primary teeth [1]. The destruction of alveolar bone in prepubertal periodontitis is more rapid than what is seen with the adult form [1].

The tooth loss exhibited in prepubertal periodontitis can be mistaken for that associated with hypophosphatasia. However in prepubertal periodontitis, which in girls is one of the most common reasons for premature exfoliation of the primary teeth, the children are seropositive for Actinobacillus actinomycetemcomitans [1].

This rare autosomal recessive disorder (OMIM #612840) is characterized by a defect associated with the white blood cells which results in a defect of their phagocytic function [13, 27–29]. The resultant defective or deficient surface protein causes poor leukocyte migration to the site of infection [15]. This leads to the impaired phagocytic function of the leukocytes and a subsequent increased risk of infection, including periodontitis [15, 22].

The clinical features of leukocyte adhesion deficiency are all related to this impaired leukocytic function. These children present with recurrent fungal and bacterial infections with impaired wound healing. Recurrent infections of the skin and otitis media are commonly seen along with necrotic infections of the gastrointestinal tract and mucous membranes [15, 27–29]. These skin infections are often without the formation of any purulence [29].

The pathologies within the oral cavity are all a function of a severe chronic infection. A severe periodontitis is present (Fig. 3.6) causing rapid alveolar bone loss. This early-onset periodontitis in the primary dentition, and the resulting rapid alveolar bone loss (Fig. 3.7) surrounding the primary teeth, is the cause of the early exfoliation of (in some cases) the entire primary dentition [15, 27–29]. A marked gingival inflammation is present around the affected teeth which includes both the primary and permanent dentitions [15, 28] (Table 3.1).