From the Guidelines
Hypophosphatasia is a rare genetic disorder, however the provided evidence is about X-linked hypophosphataemia (XLH), which is a different condition, characterized by impaired bone mineralization due to renal phosphate wasting and low serum levels of phosphate [ 1 ].
Key Features
- The diagnosis of XLH should be considered in children with clinical and/or radiological signs of rickets, impaired growth velocity, and serum levels of phosphate below the age-related reference range [ 1 ].
- In adults, the diagnosis of XLH should be considered in the presence or history of lower limb deformities, and/or clinical and/or radiological signs of osteomalacia [ 1 ].
- A detailed clinical evaluation, radiological evaluation, and biochemical tests, including serum levels of phosphate, calcium, and alkaline phosphatase, are essential for diagnosis [ 1 ].
- Genetic analysis of the PHEX gene can confirm the diagnosis of XLH, and genetic counseling is recommended for patients and families [ 1 ].
Differential Diagnosis
- Other causes of hypophosphataemic rickets, such as autosomal dominant hypophosphataemic rickets or tumour-induced osteomalacia, must be considered in patients with a negative family history or unusual clinical presentation [ 1 ].
- Renal Fanconi syndrome, dietary phosphate deficiency, and hereditary hypophosphataemic rickets with hypercalciuria are other conditions that can cause hypophosphataemia [ 1 ]. It is essential to note that the provided evidence is about X-linked hypophosphataemia, not hypophosphatasia, and the diagnosis and management of these conditions may differ.
From the FDA Drug Label
What is STRENSIQ? STRENSIQ is a prescription medicine used to treat people with perinatal, infantile, and juvenile onset hypophosphatasia (HPP).
Hypophosphatasia (HPP) is a condition that STRENSIQ is used to treat.
- HPP is mentioned as a condition that STRENSIQ is used to treat, but the drug label does not provide a detailed description of the condition itself. However, based on the context, it can be inferred that HPP is a serious medical condition that requires treatment with STRENSIQ. The drug label provides information on the treatment of HPP with STRENSIQ, including dosage and administration instructions, as well as potential side effects and warnings 2.
From the Research
Definition and Characteristics of Hypophosphatasia
- Hypophosphatasia (HPP) is a rare inherited bone disorder identified by impaired bone mineralization 3, 4, 5, 6, 7.
- It is caused by loss-of-function mutations in the ALPL gene, which encodes for tissue nonspecific isoenzyme of alkaline phosphatase (TNAP) 3, 5, 6, 7.
- The condition is characterized by defective bone and teeth mineralization, and deficiency of serum and bone alkaline phosphatase activity 5.
Subtypes of Hypophosphatasia
- There are seven subtypes of HPP, mainly characterized by their age of onset: perinatal (prenatal) benign, perinatal lethal, infantile, childhood, adult, odontohypophosphatasia, and pseudohypophosphatasia 3.
- Each subtype has distinct clinical features, such as respiratory complications, premature craniosynostosis, widespread demineralization, and rachitic changes in the metaphyses 3, 5.
Clinical Features and Diagnosis
- Clinical features of HPP include premature loss of teeth, metatarsal and subtrochanteric fractures, fragility fractures, poor bone healing, myalgias, and muscle weakness 6.
- Diagnosis is based on laboratory assays, such as serum alkaline phosphatase activity, and DNA sequencing of the ALPL gene 3, 5, 6.
- Biomarkers, especially alkaline phosphatase (ALP), are major contributors to diagnosis, but genetic testing is done for definitive diagnosis 3.
Treatment and Management
- The primary treatment for HPP is the reintroduction of TNAP as a recombinant enzyme called asfotase alfa 3, 4.
- Pharmaceutical therapies, such as bisphosphonates, denosumab, and vitamin D, are contraindicated in adults with HPP 3.
- Symptomatic treatments, such as non-steroidal anti-inflammatory drugs or teriparatide, have been shown to be of benefit 5, 6.