Diagnosing Hypophosphatasia

The diagnostic tools used often depend on the clinical form of HPP.

• Prenatal HPP: May be diagnosed through prenatal ultrasound and X-rays.
• Infantile, childhood, and adult HPP: May be diagnosed through family history, physical examination, X-rays, and laboratory results.
• Odonto HPP: May be diagnosed through physical examination, dental X-rays, and laboratory results.
• Benign Perinatal HPP: May be diagnosed through prenatal ultrasound and clinical course.

The information below provides more details about how HPP is diagnosed.

Laboratory Testing

The four strongest laboratory markers for HPP include the following: Alkaline Phosphastase: Low levels of alkaline phosphatase in the blood. In general, the lower the ALP level, the more severe the clinical symptoms of HPP. Pyridoxal 5’-phosphate (PLP): Elevated PLP level in the blood is the most sensitive marker for HPP and often correlates with disease severity. Phosphoethanolamine (PEA): Elevated level of PEA is observed in most HPP patients’ urine. Urinary inorganic pyrophosphate (PPi): Elevated PPi level is observed in most HPP patients and have been reported to accurately detect carriers, although this is typically only used in research.

Blood samples are tested for markers of HPP

X-Ray Analysis

The X-ray is a diagnostic tool for perinatal and infantile HPP. For milder cases of HPP, the combination of clinical, laboratory and X-ray findings may be required for diagnosis. Perinatal HPP: Near absence of skeletal mineralization, severe bone abnormaities. Infantile HPP: Deficient skeletal mineralization, bone abnormaities. Childhood HPP: Skeletal deformities and fractures characterize the childhood form. Adult HPP: Bilateral femoral pseudofractures are typically observed. These pseudofractures may remain for years or worsen. An increased incidence of poorly healing stress fractures, especially of the metatarsals, is also observed. Odonto HPP: X-rays appear normal, except for low bone mineral density in the jaw.

Radiographic imaging is used to examine bone abnormalities

Genetic Analysis

HPP is caused by mutations in the ALPL gene, which is the only gene known to be associated with this disease. Approximately 204 distinct mutations have been described in the literature and mutation analysis is available in several laboratories (www.genetests.org). If a patient with HPP undergoes genetic testing, a genetic counselor should be involved to provide guidance on such issues as family planning, carrier testing, and prenatal screening.

DNA Sequencing can detect genetic mutations specific for HPP