Hypophosphatasia (HPP) is a rare, inherited metabolic disorder characterized by defective mineralization of bones and teeth, leading to a range of clinical manifestations. It results from mutations in the
ALPL gene, which encodes the enzyme tissue-nonspecific alkaline phosphatase (TNSALP). This enzyme is crucial for bone mineralization and energy metabolism. In pediatrics, hypophosphatasia can present in various forms, from perinatal lethal to milder childhood forms.
Symptoms of
hypophosphatasia in children can vary widely depending on the severity of the disease. Common symptoms include:
Poor growth and short stature
Rickets, characterized by bone pain and deformities such as bowed legs
Premature loss of primary (baby) teeth
Delayed motor milestones
Weak and soft bones, leading to frequent fractures
Muscle weakness
Diagnosis of hypophosphatasia involves a combination of clinical evaluation, biochemical tests, and genetic analysis. Key diagnostic steps include:
Clinical examination for symptoms such as bone deformities and premature tooth loss
Low levels of serum alkaline phosphatase (ALP) activity
Elevated levels of substrates like
phosphoethanolamine (PEA), pyridoxal 5'-phosphate (PLP), and inorganic pyrophosphate (PPi) in blood and urine
Radiographic imaging to assess bone abnormalities
Genetic testing to identify mutations in the
ALPL gene Treatment for hypophosphatasia aims to manage symptoms and improve quality of life. It may include:
Enzyme replacement therapy (ERT) with asfotase alfa to replace deficient TNSALP
Physical therapy to improve mobility and muscle strength
Orthopedic interventions to manage bone deformities
Dental care to address premature tooth loss and other dental issues
Supportive care to manage pain and improve overall well-being
The prognosis for children with hypophosphatasia varies depending on the severity of the disorder. Early diagnosis and appropriate management can significantly improve outcomes. While severe forms of the disease can lead to serious complications and reduced life expectancy, milder forms may allow children to live relatively normal lives with appropriate care and treatment.
Since hypophosphatasia is a genetic disorder, there are no known preventive measures to avoid its occurrence. However, genetic counseling can help at-risk families understand their risks and options. Prenatal testing and carrier screening can also be considered for families with a history of hypophosphatasia.