Can you develop hypophosphatasia as an adult?

While hypophosphatasia (HPP) is a genetic disorder often diagnosed in infancy or childhood, a milder adult-onset form can certainly develop later in life. This rare inherited metabolic disease affects the mineralization of bones and teeth, leading to a spectrum of clinical manifestations that can significantly impact a person's quality of life.

Quick Summary

Adult-onset hypophosphatasia is a real and often misdiagnosed condition caused by a genetic mutation affecting bone and tooth mineralization. It can cause chronic pain, recurring fractures, and dental issues, with symptoms sometimes mirroring other common bone diseases like osteoporosis. Delayed diagnosis is common, highlighting the need for increased awareness among both patients and healthcare providers.

Key Points

• Adult-Onset HPP Exists: Hypophosphatasia can manifest for the first time in adulthood, often with symptoms previously missed in childhood.

• Often Misdiagnosed: Adult HPP is commonly mistaken for more prevalent bone conditions like osteoporosis due to overlapping symptoms.

• Diagnostic Challenge: Diagnosis requires looking beyond common ailments, with key indicators including persistently low alkaline phosphatase (ALP) and elevated PLP levels.

• Chronic Pain and Fractures: Recurring stress fractures, pseudofractures, and chronic bone and muscle pain are hallmark symptoms in adults.

• Treatment Requires Specificity: Certain osteoporosis drugs are harmful for HPP patients, and management typically involves supportive care and sometimes enzyme replacement therapy.

• Long-term Management is Key: While not always fatal like the infantile form, adult HPP can be progressive and debilitating, requiring ongoing, multidisciplinary care.

Understanding Adult-Onset Hypophosphatasia (HPP)

Hypophosphatasia, or HPP, is an inherited metabolic disorder caused by mutations in the ALPL gene. This gene provides instructions for making an enzyme called tissue-nonspecific alkaline phosphatase (TNSALP), which is critical for bone and tooth mineralization. When this enzyme is deficient, calcium and phosphate do not deposit correctly into the skeletal structures, causing them to become soft and weak—a condition known as osteomalacia in adults.

While the disease can be severe and life-threatening in its perinatal or infantile forms, the adult-onset version is often milder and can go undiagnosed for years. The variability of symptoms and its rarity make diagnosis challenging, as its signs are often mistaken for more common conditions such as osteoporosis, fibromyalgia, or arthritis.

Symptoms of Adult-Onset HPP

Adults with HPP experience a variety of symptoms that can range in severity. The presentation is highly heterogeneous, and individuals may have different combinations of musculoskeletal and dental issues.

• Chronic Pain: Persistent bone and muscle pain is a hallmark symptom, often affecting the feet, thighs, and hips.
• Recurrent Fractures: Adults with HPP may experience frequent stress fractures or pseudofractures, particularly in the feet (metatarsal bones) and thighs (femoral pseudofractures). These fractures often heal slowly or incompletely.
• Osteomalacia: The softening of bones can cause significant pain and increase the risk of fractures.
• Dental Abnormalities: A history of early loss of baby teeth is a common sign, but adults may also experience premature loss of permanent teeth due to defective dental cementum.
• Joint Issues: Joint inflammation, chondrocalcinosis (calcium crystal deposits), and osteoarthropathy can lead to significant joint pain and mobility problems.
• Muscle Weakness: Myopathy, or chronic muscle weakness, can contribute to fatigue and an altered gait.
• Mental Health Impact: Studies have shown a link between adult HPP and a higher prevalence of depression and anxiety, likely due to the chronic pain and disability.

The Diagnostic Journey

Diagnosing HPP in adults requires a careful evaluation of clinical presentation, laboratory findings, and imaging. Due to the disease's rarity, the journey to a correct diagnosis can be lengthy and frustrating.

1. Low Alkaline Phosphatase (ALP): The most consistent biochemical marker is a persistently low level of serum ALP. It is crucial to use age- and sex-adjusted reference ranges, as ALP levels naturally vary.
2. Elevated Substrates: The lack of TNSALP enzyme activity leads to an accumulation of its natural substrates, including pyridoxal 5'-phosphate (PLP, a form of vitamin B6) and phosphoethanolamine (PEA). Elevated levels of these compounds, especially PLP, can support a diagnosis.
3. Medical History: A detailed medical history is essential, including questions about childhood symptoms like early tooth loss or previous rickets.
4. Radiographic Findings: Imaging, such as X-rays, can reveal classic signs like stress fractures, pseudofractures, and chondrocalcinosis.
5. Genetic Testing: Genetic testing for mutations in the ALPL gene can confirm the diagnosis, especially in cases where biochemical results are inconclusive or inheritance patterns need clarification.

Treatment and Management

There is no cure for HPP, but treatments are available to manage symptoms and improve quality of life. The approach is often multi-faceted, involving supportive care and, in some cases, specific therapies.

• Enzyme Replacement Therapy (ERT): Asfotase alfa (Strensiq®) is the primary ERT for HPP. While it was initially approved for pediatric-onset HPP, some adult patients with pediatric-onset disease may be eligible for treatment. Treatment decisions for adult-onset HPP patients are complex and require careful consideration.
• Pain Management: Nonsteroidal anti-inflammatory drugs (NSAIDs) can be used to manage bone and joint pain. For chronic, severe pain, pain management specialists may be necessary.
• Orthopedic Interventions: Surgery, such as intramedullary rodding, may be needed to repair fractures that fail to heal properly.
• Physical Therapy: Physical therapy is crucial for restoring strength, improving mobility, and managing gait abnormalities.
• Dental Care: Regular, specialized dental care is essential due to the dental complications of HPP, including tooth loss and other abnormalities.

Comparison: Adult HPP vs. Osteoporosis

Because symptoms can overlap, adult HPP is often misdiagnosed as osteoporosis. Understanding the key differences is crucial for proper treatment, as certain osteoporosis medications (bisphosphonates) can worsen HPP symptoms.

Feature	Adult Hypophosphatasia (HPP)	Osteoporosis
Underlying Cause	Inherited genetic mutation (ALPL gene)	Multifactorial, including age-related bone loss, hormone changes, and lifestyle factors
ALP Levels	Consistently low	Typically normal or elevated
Fracture Pattern	Recurrent stress fractures (especially metatarsals) and pseudofractures in long bones (e.g., femur)	Vertebral compression fractures, hip, and wrist fractures
Dental Issues	Premature loss of permanent teeth due to poor dental cementum	Not directly related, though bone loss can affect the jaw
Bone Quality	Characterized by osteomalacia (defective mineralization)	Reduced bone density (porous bone)
Treatment Response	Requires specific management; certain drugs for osteoporosis (bisphosphonates) are contraindicated	Treated with anti-resorptive medications (bisphosphonates) or anabolic agents

The Prognosis and Future

The long-term outlook for adults with HPP is variable and depends on symptom severity and management. While milder forms may have a good prognosis, the progressive nature of the disease can lead to significant disability and reduced quality of life over time. Early and accurate diagnosis is critical to avoid inappropriate treatments and begin proper supportive care. Ongoing research, including the use of ERT in adults, offers hope for improved therapeutic strategies in the future.

For more detailed clinical information, consult reputable medical databases and resources such as the National Institutes of Health.

Conclusion

It is entirely possible for individuals to develop hypophosphatasia as an adult, with symptoms that may be a continuation of mild, undiagnosed childhood manifestations or new in adulthood. Recognizing the signs, especially chronic pain and atypical fractures combined with low ALP levels, is the key to an accurate diagnosis. Proper management, and potentially new therapies, can help mitigate the debilitating effects of this complex metabolic bone disease. Increased awareness is vital for improving the diagnostic and treatment journey for those living with adult-onset HPP.

Frequently Asked Questions

What are the first signs of developing hypophosphatasia as an adult?

The initial signs of adult-onset hypophosphatasia often include chronic bone or muscle pain, recurrent fractures (especially in the feet or thighs), and premature loss of permanent teeth. Many adults may also have a history of dental problems or mild bone issues that went undiagnosed in childhood.

How is adult hypophosphatasia different from osteoporosis?

While both conditions cause bone weakening, adult HPP is a genetic disorder characterized by defective bone mineralization and very low alkaline phosphatase (ALP) levels. Osteoporosis is a multifactorial condition involving low bone mass, and ALP levels are typically normal or elevated. Crucially, some medications for osteoporosis can worsen HPP symptoms.

Can diet help with adult-onset hypophosphatasia?

While a balanced diet rich in essential nutrients is important for overall health, there is no specific dietary regimen that can cure HPP. Patients should follow the advice of their healthcare provider, as excessive vitamin D or calcium supplements can be harmful due to the body's impaired ability to process them.

Is there a cure for adult hypophosphatasia?

Currently, there is no cure for hypophosphatasia, but treatments are available to manage symptoms and improve quality of life. The main treatment for severe pediatric-onset HPP is enzyme replacement therapy, and its use in adults is an evolving area of research.

Why is diagnosis often delayed for adults with HPP?

Delayed diagnosis for adult HPP is common because the symptoms, such as chronic pain and fractures, can be non-specific and are frequently mistaken for other more common bone or rheumatologic diseases. This can lead to years of misdiagnosis and inappropriate treatment.

Can an adult pass hypophosphatasia on to their children?

Yes. HPP is a genetic disorder caused by a mutation in the ALPL gene. It can be inherited in an autosomal recessive or dominant pattern, meaning it can be passed from parent to child. Genetic counseling is recommended for individuals with HPP who plan to have children.

What is the prognosis for someone diagnosed with adult HPP?

The prognosis is highly variable depending on the disease's severity and progression. While milder cases may cause fewer issues, the disease can lead to chronic pain, mobility problems, and disability. Proper diagnosis and supportive management can help mitigate symptoms and improve long-term quality of life.