A clinical and research protocol for characterizing patients with hypophosphatasia

Resident: Adam J. Bottrill
Date: 23AAPR10
Region: Providence
Article title: A clinical and research protocol for characterizing patients with hypophosphatasia
Author(s): Hu, ChingChun et al.
Journal: Pediatric Dentistry
Page #s: pp. 17-23
Year: 1996, 18:1
Major topic: Hypophosphatasia
Minor topic(s): NA
Type of Article: Topic Review
Main Purpose: Review and discuss science behind, and clinical characteristics of hypophosphatasia (HP).
Overview of method of research: N/A

Key points in the article discussion:

I. General:
A. Usually autosomal recessive trait with prevalence of approximately 1 in 100,000 live births.
B. Highly variable clinical manifestations.

II. Underlying Genetic Defect:
A. Defect in gene-encoding, tissue nonspecific alkaline phosphatase (TNSALP).
B. HP occurs when a single nucleotide in the coding region for the protein is mutated, causing one of the 507 amino acids to change.
C. Dx with reduction in serum alkaline phosphatase activity and elevated serum and urine levels of TNSALP substrates.
D. There has been one documented case of “pseudo AP”.
E. Most severe forms of AP are recessive and usually lethal at or near birth.

III. Clinical Manifestations of TNSALP Mutations:
A. Classified according to age it first manifests itself. Usually the earlier the appearance of symptoms, the more severe it is.
B. Four clinical varieties: perinatal, infantile, childhood and adult onset..
1. Perinatal: occurs in utero with stillborn or death soon after.
2. Infantile: Similar skeletal deformities, but less severe. Dx based on radiograph. Flail chest, pneumonia, blue sclerae, harlequin orbits, pathologic lid retraction.craniosynostosis, premature tooth loss. Ossification defects.
3. Childhood: often first Dx by the dentist. Rickets, small stature, waddling gait, partial or complete lack of cementum formation which leads to malformation of PDL. Both parents likely to have the serum/urine characteristics. Bony deformities.
4. Adult: premature loss of teeth, Hx of early primary tooth loss, enamel hypoplasia, craniosynostosis, pseudogout.

IV. Role of Pediatric Dentist:
A. Often the first member of a health care team to make a Dx.
B. Referral may lead to Dx and can be a strong tool.

V. Proposed Clinical Approach:
A. Patient and family Hx (pedigree), with serum and urine analysis.
B. Physical exam including Ht and Wt to follow growth. Pano to track tooth loss.
C. Tissue collection. Teeth that have been extracted or prematurly lost may be submitted for histological examination.
D. Blood and urine samples.
E. Recall

Assessment of article: Effective article, however not as “dentistry specific” as I’d hoped. However, through accurate description of future cases, we can track and better understand the disease. No shenanigans.