Table 6.

Hereditary Disorders in the Differential Diagnosis of Adult-Onset Hypophosphatasia and Odontohypophosphatasia

GeneDisorderMOIClinical Features / Comment
C1R
C1S
COL3A1 		Familial periodontal disease as part of connective tissue disorder (e.g., vascular Ehlers-Danlos syndrome [EDS] or periodontal EDS)AD
(AR 1)		Periodontal EDS may present w/root-intact tooth loss, the distinction being low serum ALP in odontohypophosphatasia.
CTSC Aggressive periodontitis 1 (OMIM 170650)ARFamilial periodontal disease
Papillon-Lefevre syndrome (OMIM 245000)ARRarer disorders assoc w/premature tooth loss & periodontal disease. The periodontal disease is usually earlier in onset & more severe than that seen w/odontohypophosphatasia. Both Papillon-Lefevre syndrome & HMS are usually assoc w/palmar keratosis, further distinguishing them from odontohypophosphatasia. Measurement of serum ALP enzyme activity is reasonable when either disorder is considered.
Haim-Munk syndrome (HMS) (OMIM 245010)AR
DSPP Dentinogenesis imperfecta (OMIM DSPP Clinical Synopsis)ADDentinogenesis imperfecta is readily distinguishable from odontohypophosphatasia on biochemical findings.
ELANE Familial periodontal disease assoc w/neutropenia (e.g., ELANE-related neutropenia)ADELANE-related neutropenia includes congenital neutropenia & cyclic neutropenia, both of which are primary hematologic disorders characterized by recurrent fever, skin & oropharyngeal inflammation (e.g., mouth ulcers, gingivitis, sinusitis, & pharyngitis), & cervical adenopathy.

AD = autosomal dominant; ALP = alkaline phosphatase; AR = autosomal recessive; MOI = mode of inheritance

1.

Vascular EDS is almost always inherited in an autosomal dominant manner, but rare examples of biallelic inheritance have been reported.

From: Hypophosphatasia

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