Hypophosphatasia
Hypophosphatasia (/ˌhaɪpoʊˈfɒsfeɪtˌeɪʒə/; also called deficiency of alkaline phosphatase, phosphoethanolaminuria, or Rathbun's syndrome; sometimes abbreviated HPP) is a rare, and sometimes fatal, inherited metabolic bone disease. Clinical symptoms are heterogeneous, ranging from the rapidly fatal, perinatal variant, with profound skeletal hypomineralization, respiratory compromise or vitamin B6 dependent seizures to a milder, progressive osteomalacia later in life. Tissue non-specific alkaline phosphatase (TNSALP) deficiency in osteoblasts and chondrocytes impairs bone mineralization, leading to rickets or osteomalacia. The pathognomonic finding is subnormal serum activity of the TNSALP enzyme, which is caused by one of 388 genetic mutations identified to date, in the gene encoding TNSALP. Genetic inheritance is autosomal recessive for the perinatal and infantile forms but either autosomal recessive or autosomal dominant in the milder forms.
| Hypophosphatasia | |
|---|---|
| Other names | Phosphoethanolaminuria; Rathbun's syndrome |
| Ribbon diagram of the alkaline phosphatase protein, which is deficient in individuals with hypophosphatasia | |
| Pronunciation |
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| Specialty | Orthopedics, pediatrics, endocrinology |
| Symptoms | Variable—may include osteopenia, skeletal hypomineralization, respiratory compromise |
| Onset | Birth |
| Duration | Lifelong |
| Types | Infantile, childhood, adult, and odontohypophosphatasia |
| Causes | Mutation of the ALPL gene |
| Diagnostic method | Comprehensive metabolic panel test for serum alkaline phosphatase level; examination of X-rays; genetic tests of ALPL |
| Differential diagnosis | Osteogenesis imperfecta, congenital dwarfisms, skeletal dysplasias |
| Treatment | Asfotase alfa (Strensiq), an enzyme replacement therapy |
| Prognosis | Severe perinatal forms are lethal without treatment; adult forms may only show moderate symptoms |
| Frequency | Rare (1 in 100,000); more common in some populations |
The prevalence of hypophosphatasia is not known; one study estimated the live birth incidence of severe forms to be 1:100,000. and some studies report a higher prevalence of milder disease.