Hypophosphatemic Rickets

Hypophosphatemic Rickets is a group of rare disorders that affect the way the body processes phosphate, a mineral essential for healthy bones and teeth. Unlike nutritional rickets, which results from vitamin D deficiency, hypophosphatemic forms of rickets are typically inherited and involve phosphate-wasting, where the kidneys are unable to retain enough phosphate, leading to weakened, softened bones.

At Brighter Hope Foundation, we focus on providing accessible, accurate information about Autosomal Recessive Hypophosphatemic Rickets Type 2 (ARHR2), a rare condition linked to ENPP1 Deficiency. To help families better understand where ARHR2 fits within the broader medical landscape, this page offers a general overview of Hypophosphatemic Rickets, including its various types, symptoms, diagnosis, and treatments.

What Is Hypophosphatemic Rickets?

Hypophosphatemic Rickets is almost always caused by genetic mutations that interfere with the body’s ability to balance phosphate. Phosphate is critical for proper bone formation and strength. When the kidneys excrete too much phosphate, bones can become soft and prone to deformities, a hallmark of rickets.

There are several known genetic subtypes of Hypophosphatemic Rickets, each with distinct causes and treatment approaches:

Common Forms of Hypophosphatemic Rickets

  • Autosomal Recessive Hypophosphatemic Rickets Type 2 (ARHR2): Caused by mutations in the ENPP1 gene, the same gene involved in Generalized Arterial Calcification of Infancy (GACI). While ARHR2 is a focus of Brighter Hope Foundation’s mission, it represents just one subset of Hypophosphatemic Rickets.
  • X-Linked Hypophosphatemia (XLH): The most common form, caused by mutations in the PHEX gene. It is typically inherited in an X-linked dominant pattern and often treated with therapies such as burosumab (a monoclonal antibody that targets FGF23). This treatment is not suitable for patients with ARHR2 and can cause or worsen calcifications.
  • Autosomal Dominant Hypophosphatemic Rickets (ADHR): Caused by mutations in the FGF23 gene. Symptoms can be variable and sometimes appear later in life.
  • Autosomal Recessive Hypophosphatemic Rickets Type 1 (ARHR1): Linked to mutations in the DMP1 gene.

Each form of Hypophosphatemic Rickets may require different diagnostic tools and treatments. Understanding the specific genetic cause is crucial for determining the most appropriate care.

Diagnosis

Diagnosis typically begins with:

  • Blood and urine tests: These may reveal low phosphate levels, high levels of alkaline phosphatase, and evidence of phosphate wasting in the urine.
  • X-rays: Used to identify bone abnormalities characteristic of rickets.
  • Genetic testing: Essential for identifying the specific subtype of Hypophosphatemic Rickets. This helps guide treatment decisions and informs family planning and genetic counseling.

Families with a history of rickets or unexplained bone deformities should consider genetic evaluation.

Treatment

The primary goal of treatment is to restore phosphate balance and support healthy bone growth and development. However, treatment strategies vary depending on the Hypophosphatemic Rickets subtype. Common treatments include:

  • Oral phosphate supplements: These help increase blood phosphate levels.
  • Active forms of vitamin D (such as calcitriol or alfacalcidol): These enhance the absorption of phosphate and calcium from the digestive tract.
  • Burosumab therapy: This is specifically approved for XLH, and not recommended for all types of Hypophosphatemic Rickets (can cause or worsen calcification in patients with ARHR2.)
  • Orthopedic interventions: In some cases, surgical correction may be needed for severe bone deformities.

Treatment must be tailored to the specific Hypophosphatemic Rickets subtype. For example, therapies like burosumab, which are effective in XLH, may not be safe or effective for ARHR2 and could even worsen complications such as vascular calcification.

Join Our Community

Whether you’re newly diagnosed with ARHR2 or have been on the journey for years, we invite you to connect with others through our support network. Learn from shared experiences, ask questions, and find hope in a community that truly understands.

For more information, please contact us or explore additional resources on our website.