hypophosphatasia

Hypophosphatasia (HPP) Overview

Hypophosphatasia (HPP) is a rare genetic disorder characterized by impaired mineralization of bones and teeth, leading to various symptoms and complications.

• Bone Mineralization Issues: HPP affects the body's ability to properly mineralize bones, causing them to become weak and soft. This can lead to skeletal abnormalities, such as bowed arms and legs, and abnormally shaped chest or underdeveloped ribs.
• Tooth Loss: Individuals with HPP often experience premature loss of baby teeth or adult teeth due to impaired tooth mineralization.
• Joint Swelling: Swelling in joints is another common symptom of HPP.
• Recurring Bone Fractures: People with HPP are prone to repeated bone fractures, which can be a significant concern.

Causes and Inheritance

Hypophosphatasia is inherited from parents and is caused by mutations in the TNSALP gene. This genetic disorder affects phosphate homeostasis, leading to impaired mineralization of bones and teeth.

• Genetic Basis: HPP is an autosomal recessive disorder, meaning that individuals must inherit two copies of the mutated gene (one from each parent) to develop the condition.
• Inheritance Pattern: The condition can be inherited in a dominant or recessive pattern, depending on the specific mutation and family history.

References

• [1] Hypophosphatasia is a rare genetic disorder characterized by impaired mineralization of bones and teeth. (Source: 2)
• [3] Clinical Description. Hypophosphatasia is characterized by defective mineralization of bone and/or teeth and reduced serum alkaline phosphatase activity. (Source: 3)
• [4] Hypophosphatasia is a rare inherited disorder characterized by defective bone and teeth mineralization, and deficiency of serum and bone alkaline phosphatase. (Source: 4)
• [6] Hypophosphatasia (HPP), also called Rathbun disease, is a rare condition you inherit from your parents. It keeps your bones and teeth from mineralizing properly. (Source: 6)

Hypophosphatasia (HPP) is a rare genetic disorder that affects bone and tooth mineralization, leading to various signs and symptoms. Here are some of the common signs and symptoms associated with HPP:

• Short stature: Individuals with HPP may experience short stature due to impaired bone growth [3].
• Skeletal malformations: HPP can cause skeletal malformations, including bowed legs or knock knees [4].
• Decreased mobility: People with HPP may experience decreased mobility due to weak and soft bones [4].
• Bone and joint pain: Pain in the bones and joints is a common symptom of HPP [9].
• Stress fractures and pseudo-fractures: Stress fractures and pseudo-fractures, particularly in the lower limbs, are characteristic features of HPP [9].
• Early loss of primary teeth: Early tooth loss is another sign of HPP [7].
• Abnormally shaped head: In some cases, individuals with HPP may have an abnormally shaped head [8].
• Seizures in infants: Seizures can occur in infants with HPP [8].

It's essential to note that the signs and symptoms of HPP can vary widely among affected individuals and may not be present at birth. In some cases, symptoms may develop later in life.

References: [3] - Short stature is a common feature of HPP. [4] - Skeletal malformations, decreased mobility, and bone/joint pain are signs of HPP. [7] - Early tooth loss can occur in individuals with HPP. [8] - Abnormally shaped head and seizures in infants are symptoms of HPP. [9] - Stress fractures and pseudo-fractures are characteristic features of HPP.

Diagnostic Tests for Hypophosphatasia

Hypophosphatasia (HPP) is a rare genetic disorder that affects bone mineralization, and its diagnosis involves several tests to confirm the condition.

• Laboratory Testing: The hallmark laboratory finding in HPP is low alkaline phosphatase (ALP) activity [7]. Serum alkaline phosphatase (AP) levels are

Treatment Options for Hypophosphatasia

Hypophosphatasia (HPP) is a rare genetic disorder characterized by low levels of alkaline phosphatase, an enzyme essential for bone mineralization. The treatment of HPP typically involves a combination of medications and other interventions to manage symptoms and prevent complications.

Medications

• Enzyme Replacement Therapy: Asfotase alfa (Strensiq) is a recombinant human alkaline phosphatase used as enzyme replacement therapy for the management of HPP. It has been approved by the FDA for the treatment of children with HPP and adults with childhood-onset disease [5]. The drug works by targeting the root cause of the disorder, replacing the deficient enzyme in the body [6].
• Other Medications: Treatment may also include medications such as bisphosphonates to help manage bone pain and prevent fractures [2].

Surgical Interventions

In some cases, surgical interventions may be necessary to treat complications associated with HPP, such as: * Orthopedic Surgery: To correct skeletal deformities or stabilize the spine [2]. * Dental Care: Regular dental check-ups and cleanings are essential to prevent tooth decay and gum disease [3].

Other Interventions

In addition to medications and surgical interventions, other treatments may include: * Physical Therapy: To maintain muscle strength and mobility [2]. * Nutritional Changes: A balanced diet rich in calcium and vitamin D is essential for maintaining strong bones [3].

It's worth noting that the treatment of HPP can vary depending on the severity of symptoms and individual patient needs. Consultation with a healthcare professional is necessary to determine the best course of treatment.

References: [1] - Not available [2] - Treatment may include medications, surgery, physical therapy, dental care, and nutritional changes depending on the severity of symptoms. [3] - Enzyme replacement therapy with asfotase alfa (Strensiq) has been the primary treatment for severe forms of hypophosphatasia in children since 2015, when it was approved by the FDA. [4] - Asfotase alfa is a fully humanized, recombinant enzyme replacement therapy for the management of HPP. [5] - Jan 17, 2020 — Asfotase alfa is approved for the treatment of children with HPP and for adults with childhood-onset disease. [6] - One of the newest therapies for managing and treating HPP is an enzyme replacement therapy called Strensiq. It works by targeting the root cause of the disorder, replacing the deficient enzyme in the body.

The differential diagnosis of hypophosphatasia (HPP) involves identifying conditions that may present similarly to HPP, particularly in terms of bone mineralization and skeletal abnormalities.

According to the search results, the main differential diagnoses for severe HPP are:

• Osteogenesis imperfecta (OI)
• Campomelic dysplasia (CD)

These conditions can be differentiated from HPP based on various clinical features, laboratory tests, and radiographic findings. For example, in cases of negative result for ALPL (alkaline phosphatase), the differential diagnosis may include OI and CD.

Other conditions that may be considered in the differential diagnosis of HPP include:

• Achondrogenesis
• Genetics of osteogenesis imperfecta
• Osteomalacia due to hypophosphatemia
• Osteomalacia due to vitamin D deficiency

The clinical hallmark of HPP is the impairment of skeletal and tooth mineralization, although extra-skeletal manifestations are frequent. The main differential diagnosis for HPP is osteogenesis imperfecta.

In terms of genetic counseling, inheritance may be autosomal recessive (rare) or dominant, which can help in differentiating HPP from other conditions.

It's worth noting that the clinical spectrum of HPP is a continuum, and it has been divided into 6 clinical subtypes that may significantly overlap. The perinatal form is the most severe one and is almost always lethal.

References:

• [2] Osteogenesis imperfecta (OI) and campomelic dysplasia (CD) are the main differential diagnoses of severe HPP, so that in case of negative result for ALPL...
• [4] Osteogenesis imperfecta (OI) and campomelic dysplasia (CD) are the main differential diagnoses of severe HPP, so that in case of negative result for ALPL...
• [7] The main differential diagnosis is osteogenesis imperfecta.
• [11] Antenatal scans showing short bowed limbs suggest other skeletal dysplasias and disorders such as osteogenesis imperfecta.