D. Wenkert, M. Benigno, K. Mack, W. McAlister, S. Mumm, M. Whyte

Hypophosphatasia (HPP) is caused by deactivating mutations in the gene that encodes the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). Patients have extracellular accumulation of inorganic pyrophosphate (a TNSALP substrate) which inhibits skeletal mineralization. Subtypes of pediatric HPP include infantile HPP (diagnosed < 6 mo of age), childhood HPP (diagnosed > 6 mo with obvious skeletal disease), mild childhood HPP (subtle rickets), and odonto-HPP (dental manifestations only). Children with odonto-HPP seek medical attention for early tooth loss (< 5 yr old).  There is no established medical treatment.

We previously reviewed 111 of our 177 pediatric HPP patient charts to characterize their skeletal and joint pain (JBMR 19:S487, 2004) and found that this problem paralleled the severity of their disease assessed biochemically, radiographically, etc.  In general, this complication interfered with physical activity in only the most severely affected patients.

Here, we report the prevalence of additional important complications of pediatric HPP using our data accumulated over the past 25 years from inpatient follow-up evaluations (at 4 mo - 21 yr). We utilized all information from 175 of our 177 patients, excluding those 2 who had received bone marrow transplantation in infancy. Table I summarizes information available concerning most of the patients, where prevalence is reported as a percentage of the patients for whom there was data. Some patients were reported twice if their genu varum later became genu valgum. Additional complications not specifically evaluated in > 50 % of patients, but of significant prevalence, are described as % of our total HPP population (Table II).

Premature primary tooth exfoliation (98%), joint hypermobility (93%), lower extremity malalignment (73%), and skeletal pain (70%) troubled the majority of our patients. Muscle weakness, craniosynostosis, chest deformities, scoliosis, clubfoot, and fractures also occurred with increased frequency. Although nearly 1/3rd of our patients had sustained a fracture, only 7% had multiple fractures. Fracture healing rates, however, were often prolonged.

The prevalences for the most common complications of pediatric HPP parallel the age-of-onset of the disease, with the more severe infantile form having earlier tooth loss, greater reporting of frequent fractures and bone or joint pain, a greater delay in walking, and degree of weakness.

Disclosures: M. Whyte, Enobia Pharma, Montreal Canada: Consulting Fees or Other Remuneration. D. Wenkert, Enobia Pharma, Montreal Canada: Research Grants.

Attachments

Table 1

Table 2