Hypophosphatasia

Overview

Board takeaway: Refer painless primary tooth loss with intact roots for metabolic assessment; preserve remaining teeth and plan replacement that accommodates growth. Inherited deficiency of tissue-nonspecific alkaline phosphatase impairs mineralization of bone and cementum.

How does Hypophosphatasia affect dental management?

• Referral: Refer to the pediatrician or geneticist; the dentist is often first to suspect it
• Prevention: Maintain excellent hygiene and frequent recalls to preserve remaining teeth
• Rehabilitation: Replace lost teeth with removable partial dentures for function, speech, and esthetics; adjust as the child grows
• Permanent teeth: may be clinically normal in mild disease but can develop periodontitis and early loss in severe disease; monitor the permanent dentition.
• Orthodontics: use caution because cementum defects compromise attachment.
• Histology: Consider sending exfoliated teeth for histology

Exam pearl

What is Hypophosphatasia?

A rare inherited disorder caused by mutations in the ALPL gene that lower alkaline phosphatase activity, impairing mineralization of bones and teeth.

What are the main systemic features of Hypophosphatasia?

• Spectrum: Severity ranges from lethal perinatal forms to childhood, adult, and odontohypophosphatasia (teeth only)
• Laboratory pattern: Low serum alkaline phosphatase with elevated substrates (pyridoxal 5'-phosphate, phosphoethanolamine)
• Childhood form: rickets-like bone changes, fractures, short stature, delayed walking, bone pain
• Infant finding: Craniosynostosis in some infants
• Treatment: Enzyme replacement therapy (asfotase alfa) for severe pediatric forms

What oral findings occur in Hypophosphatasia?

• Premature exfoliation of primary teeth with intact roots, often the incisors first
• Absent or hypoplastic cementum, so the periodontal ligament cannot attach
• Alveolar bone loss, enlarged pulp chambers, and thin dentin in some patients
• Little gingival inflammation relative to the tooth loss

How do you distinguish Hypophosphatasia from other causes of early tooth loss?

• Hypophosphatasia: intact roots with low alkaline phosphatase.
• Neutropenia, leukocyte adhesion deficiency, and Papillon–Lefèvre syndrome: inflammatory periodontitis with infections; Papillon–Lefèvre also causes skin lesions.
• Langerhans cell histiocytosis: “floating teeth” from lytic lesions.
• Other considerations: trauma and abuse.

Sources

• AAPD dental guidance: AAPD: Systemic diseases and syndromes that affect the periodontium
• Definition: MedlinePlus Genetics: Hypophosphatasia
• Systemic Diseases and Syndromes that Affect the Periodontium
• Common Laboratory Values