Rare Disease Report

Hypophosphatasia and Dental Care

FEBRUARY 17, 2016
Mark Cannon, DDS, MS
Hypophosphatasia is a rare metabolic bone and dental disease and in perinatal cases, almost always fatal. Clinical symptoms are heterogeneous, ranging from the rapidly fatal perinatal variant, with profound skeletal hypomineralization and respiratory compromise, to a milder but progressive version later in life. Tissue non-specific alkaline phosphatase (TNSALP) deficiency in osteoblasts and chondrocytes impairs bone mineralization, leading to rickets or osteomalacia.

The pathognomonic finding is subnormal serum activity of the TNSALP enzyme, which is caused by one of 300 genetic (75% missense) mutations identified to date in the gene ALPL (on short arm of chromosome one) encoding TNSALP. Genetic inheritance is autosomal recessive for the perinatal and infantile forms but either autosomal recessive or autosomal dominant in milder forms. The prevalence of hypophosphatasia is not known. One study estimated the live birth incidence of severe forms to be 1:100,000.

Hypomineralization = Dental Problems

Early tooth loss is one of the diagnostic characteristics of hypophosphatasia. In addition, patients present with a delayed and defective mineralization of the dentition, together with a deficiency of acellular cementum. Early tooth loss of the primary dentition may occur due to the lack of acellular cementum which provides for periodontal ligament attachment to the roots of the teeth.

The dentin is dysplastic, often with large pulpal chambers. There may be inflammation of the gingiva, and an increased caries incidence.  
Odontohyposphosphatasia only presents with obvious dental involvement and is often misdiagnosed. Typically, it is diagnosed as Dentinogenesis imperfecta, molar incisor hypomineralization, periodontal disease, or rickets.

Early Diagnosis of HPP By Dentist Can Improve Outcomes

The dental examination by the pediatric dental specialists is key to diagnosing HPP early to allow for appropriate treatment. Delayed diagnosis can result in serious and unnecessary medical problems.

Being cognizant of the clinical presentation of HPP and the need for the genetic consultation is essential. Usually, the patient’s primary care physician is unaware of this rare disorder. Careful interpretation of the serum TNSALP level is important because the levels are often reported as normal by the laboratory disregarding that ALP activity is sex and age dependent.

Increased awareness of the dental complications is important but the clinician must also be well versed in the preventive protocol best suited for HPP patients.

Bacterial Growth and HPP

Whenever there is a change in the structure and surface of the dentition there is always a shift in the microbiome. Often, a more porous or textured surface encourages anaerobic growth and promotes bacterial colonization. In those situations there is typically an increase in Scardovia wiggsiae and Slackia exigua both associated with an increased risk of dental pathology. Xylitol products would seemingly be very indicated in HPP patients due to the disruption of the pathogenic biofilm. In addition, xylitol is a calcium carrier, possibly aiding in the mineralization of the hypomineralized dentition.
The use of MI Paste with casein phosphopeptide and amorphous calcium phosphate would, on the surface appear contraindicated due to the potential increase in serum levels of calcium and phosphate, but this has never been demonstrated. Judicious use by the parent may be recommended to prevent further destruction of the dentition. Probiotics, such as Evora by Oragenics, are indicated because the Streptococci uberis, oralis and ratti constituents are non-invasive inhibitors of many oral pathogens due to bacteriocin and hydrogen peroxide production.

FDA Approved HPP Treatment and Dental Health

FDA approval of Strensiq (asfotase alfa) following positive results in clinical trials has provided for efficient and safe treatment of HPP. Besides the improvement in skeletal mineralization, there has been a dental benefit from Strensiq injections.

Animal studies with Stensiq have shown the drug to improve molar tooth development, dentin and tooth morphology. The cementum, however, did remain insufficient and alveolar bone mineralization was reduced compared to the controls. Never the less, the animals did have periodontal attachment and retained teeth.

Concluding Remarks

Dentist often the first person to see the symptoms of HPP. Cognizant of early symptoms can improve outcomes. Treatments are available that can improve bone and oral health.

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