Infantile Hypophosphatasia
Disease Details
Family Health Simplified
- Description
- Infantile hypophosphatasia is a rare, inherited metabolic disorder characterized by defective bone mineralization leading to skeletal abnormalities, respiratory complications, and high calcium levels in the blood.
- Type
- Infantile hypophosphatasia is a genetic disorder that is typically inherited in an autosomal recessive pattern.
- Signs And Symptoms
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Infantile hypophosphatasia is a rare metabolic bone disorder that appears within the first six months of life.
**Signs and symptoms** include:
- Poor feeding
- Failure to thrive
- Delayed motor skills like lifting the head or sitting up
- Respiratory complications
- Hypercalcemia (elevated blood calcium levels)
- Seizures
- Early loss of primary (baby) teeth
- Weak and soft bones, leading to fractures and deformities such as bowing of the legs
This condition can significantly impact development and overall health, often requiring medical intervention. - Prognosis
- Infantile hypophosphatasia (HPP) varies widely in prognosis. Severe forms can be life-threatening, with symptoms appearing in utero or shortly after birth, often leading to respiratory complications and poor bone development. Milder forms may allow for longer survival with varying degrees of disability. Novel enzyme replacement therapies have shown promise, potentially improving outcomes. Early diagnosis and intervention are critical.
- Onset
- Onset for infantile hypophosphatasia typically occurs within the first six months of life.
- Prevalence
- Infantile hypophosphatasia is a rare genetic disorder. Its overall prevalence is estimated to be approximately 1 in 100,000 live births. It is characterized by defective bone mineralization and a variety of other symptoms due to mutations in the ALPL gene, which encodes the enzyme tissue nonspecific alkaline phosphatase.
- Epidemiology
- Infantile hypophosphatasia is a rare inherited disorder characterized by defective bone mineralization and a deficiency of alkaline phosphatase. Epidemiologically, it affects fewer than 1 in 100,000 live births. The condition can vary widely in severity, even among affected individuals within the same family.
- Intractability
- Infantile hypophosphatasia is generally considered an intractable or difficult-to-treat condition due to its genetic nature and the severe complications that often arise. This form of hypophosphatasia can lead to significant skeletal abnormalities, respiratory issues, and potentially fatal outcomes. Recent advances in enzyme replacement therapy, such as asfotase alfa, have shown promise in managing the disease, but it remains a challenging condition to fully treat or cure.
- Disease Severity
- Infantile hypophosphatasia is a rare genetic disorder affecting bone development. The severity is highly variable, ranging from mild cases where symptoms may not be evident until later in life, to severe cases that manifest shortly after birth. The severe form can be life-threatening, characterized by profound skeletal hypomineralization, respiratory complications, and high mortality rates in infancy.
- Healthcare Professionals
- Disease Ontology ID - DOID:0110914
- Pathophysiology
- Infantile hypophosphatasia is a genetic disorder caused by mutations in the ALPL gene, which encodes the tissue non-specific alkaline phosphatase (TNSALP). This enzyme is crucial for bone mineralization. Mutations lead to reduced or absent TNSALP activity, resulting in the accumulation of substrates like inorganic pyrophosphate that inhibit bone mineralization. Consequently, affected individuals experience defective bone formation, leading to skeletal abnormalities, rickets, and other systemic complications.
- Carrier Status
- Carrier status of infantile hypophosphatasia is related to the inheritance of mutations in the ALPL gene. Hypophosphatasia is typically inherited in an autosomal recessive manner for severe forms like infantile hypophosphatasia. This means that an individual must inherit two defective copies of the ALPL gene (one from each parent) to exhibit the disease. Carriers, having only one mutated copy of the gene and one normal copy, typically do not show symptoms of the condition.
- Mechanism
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Infantile hypophosphatasia is primarily caused by mutations in the ALPL gene, which encodes the enzyme tissue-nonspecific alkaline phosphatase (TNSALP). This enzyme is crucial for bone mineralization and the breakdown of certain phosphocompounds.
**Mechanism:**
The ALPL gene mutations lead to reduced or absent TNSALP activity. This deficiency impairs the breakdown of inorganic pyrophosphate (PPi), a natural inhibitor of mineralization. Elevated levels of PPi prevent proper bone formation, leading to rickets and osteomalacia.
**Molecular Mechanisms:**
1. **Enzyme Deficiency:** Mutations in the ALPL gene reduce the functional TNSALP enzyme levels.
2. **Metabolic Imbalance:** Insufficient TNSALP activity results in the accumulation of PPi.
3. **Bone Mineralization Defect:** High PPi concentrations inhibit hydroxyapatite crystal formation, essential for bone and tooth mineralization.
4. **Substrate Accumulation:** Other substrates, such as phosphoethanolamine and pyridoxal 5'-phosphate, also accumulate due to the enzyme deficiency, contributing to the disease phenotype.
These mechanisms collectively result in the skeletal abnormalities and other symptoms characteristic of infantile hypophosphatasia. - Treatment
- Treatment for infantile hypophosphatasia typically involves enzyme replacement therapy. The most commonly used treatment is asfotase alfa (Strensiq), which helps replace the deficient enzyme alkaline phosphatase. This addresses the underlying cause of the disease and improves symptoms. In severe cases, supportive care such as respiratory support, pain management, and physical therapy may also be necessary to manage complications. Regular monitoring by a healthcare team specializing in metabolic or bone disorders is essential.
- Compassionate Use Treatment
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Infantile hypophosphatasia is a rare genetic disorder affecting bone mineralization. As for compassionate use and experimental treatments:
1. **Compassionate Use Treatment:**
- **Asfotase Alfa (Strensiq):** This enzyme replacement therapy is approved in some regions for patients with infantile and juvenile-onset hypophosphatasia. For patients who do not meet these criteria, it may be available through compassionate use programs.
2. **Off-label or Experimental Treatments:**
- **Bone Marrow Transplantation (BMT):** Although not a standard treatment, BMT has been explored in a limited number of cases.
- **Gene Therapy:** Research is ongoing to explore gene therapy as a potential long-term solution for hypophosphatasia.
- **Bisphosphonates:** Sometimes used off-label to treat related symptoms, though their use remains controversial and not widely accepted for hypophosphatasia.
It's important to consult specialized healthcare providers for the most current and personalized treatment options. - Lifestyle Recommendations
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Infantile hypophosphatasia is a rare genetic disorder that affects bone mineralization. While specific lifestyle recommendations should be tailored to each individual by healthcare providers, general advice may include:
1. **Nutritional Support**:
- Ensure adequate intake of nutrients, especially calcium and vitamin D, to support bone health.
2. **Physical Therapy**:
- Engage in regular physical therapy to maintain muscle strength and improve mobility, as approved by a healthcare provider.
3. **Medical Monitoring**:
- Regular follow-ups with specialists, including pediatricians, endocrinologists, and geneticists, to monitor disease progression and manage symptoms.
4. **Avoid High-Risk Activities**:
- Limit activities that might put excessive stress on bones to prevent fractures or other injuries.
5. **Medication Adherence**:
- Follow prescribed treatments, which may include enzyme replacement therapy or other medications to manage symptoms and improve quality of life.
6. **Supportive Equipment**:
- Use of braces, walkers, or other supportive devices if recommended, to assist with mobility and decrease the risk of falls.
Always consult a healthcare professional for personalized guidance and treatment planning. - Medication
- As of my knowledge cutoff, there is a medication called asfotase alfa (brand name Strensiq) approved for the treatment of infantile hypophosphatasia. It is an enzyme replacement therapy designed to provide a synthetic form of the alkaline phosphatase enzyme, which is deficient in individuals with hypophosphatasia. This medication helps improve bone mineralization and overall health outcomes in affected infants. Always consult with a healthcare professional for the most current and personalized treatment options.
- Repurposable Drugs
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For infantile hypophosphatasia, repurposable drugs are limited but some existing treatments used off-label include:
1. **Bisphosphonates**: Such as pamidronate, although they can be used, their benefits are controversial and not always effective.
2. **Enzyme Replacement Therapy**: Asfotase alfa (Strensiq) is a more specific treatment, though not originally developed for this purpose, it addresses the enzyme deficiency directly.
Research is ongoing, and consultation with a healthcare provider is essential for treatment planning. - Metabolites
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Infantile hypophosphatasia is characterized by abnormal levels of specific metabolites. Key metabolites involved include:
1. **Low blood and bone alkaline phosphatase (ALP) activity**: This enzyme is crucial for bone mineralization.
2. **Elevated plasma and urinary levels of pyridoxal 5'-phosphate (vitamin B6)**: Due to insufficient ALP activity, this vitamin can accumulate in the body.
3. **High urinary phosphoethanolamine (PEA)**: Elevated levels of this substrate are typically excreted in the urine.
4. **Inorganic pyrophosphate (PPi)**: This compound may accumulate due to lack of ALP activity, contributing to defective bone mineralization.
Monitoring these metabolites helps in diagnosing and managing infantile hypophosphatasia. - Nutraceuticals
- Infantile hypophosphatasia is a rare genetic condition affecting bone development due to defective mineralization. Nutraceuticals are not standard treatments for this condition. Instead, management typically involves enzyme replacement therapy with asfotase alfa. It is crucial to consult healthcare providers for appropriate diagnosis and treatment plans.
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