🧬 Genetic Disorder

Hypophosphatasia

Also known as: HPP, Rathbun's disease, Phosphoethanolaminuria

Hypophosphatasia (HPP) is a rare genetic metabolic disorder characterized by defective bone mineralization. This defect results from a deficiency of the enzyme tissue-nonspecific alkaline phosphatase (TNSALP). The severity of HPP varies widely, ranging from stillbirth without mineralized bone to pathological fractures in adulthood. Clinical manifestations primarily affect the skeleton and teeth, but can also involve other organ systems.

ICD-10: E83.3 Orphanet: 434 OMIM: 146300
👥 1 in 100,000 live births (severe forms); carrier frequency estimated at 1 in 300 in European populations Prevalence
🔬 15 Active Trials

Imagine your bones need special glue to become strong. In hypophosphatasia, your body doesn't make enough of that glue, so your bones and teeth can be weak and break easily. Doctors can give you medicine to help make the glue and keep your bones strong!

Signs & Symptoms

  • Skeletal deformities (e.g., bowed legs, knock knees)
  • Rickets (in children)
  • Osteomalacia (in adults)
  • Fractures (especially of the long bones)
  • Premature loss of deciduous teeth
  • Craniosynostosis (premature fusion of skull bones)
  • Seizures (especially in infantile HPP)
  • Muscle weakness
  • Bone pain
  • Nephrocalcinosis (calcium deposits in the kidneys)
  • Respiratory complications (in severe infantile HPP)
  • Failure to thrive (in infantile HPP)

Treatment Options

MEDICATION FDA Approved

Enzyme Replacement Therapy (Asfotase Alfa)

HIGHLY EFFECTIVE Approved 2015
MEDICATION FDA Approved

Vitamin B6 (Pyridoxine)

SUPPORTIVE
MEDICATION FDA Approved

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

SUPPORTIVE
SURGERY

Orthopedic Management (Fracture care, bracing)

SUPPORTIVE
SUPPORTIVE

Dental Care

SUPPORTIVE
THERAPY

Physical Therapy

SUPPORTIVE

Diagnosis

  • Serum alkaline phosphatase (ALP) measurement (low levels)
  • Genetic testing for ALPL gene mutations
  • Radiographic imaging (X-rays, bone densitometry) to assess bone mineralization
  • Urine phosphoethanolamine (PEA) measurement (elevated levels)
  • Bone biopsy (rarely needed)

History

Hypophosphatasia was first described by Dr. John Campbell Rathbun in 1948 in a Canadian pediatrician journal. He described a severe form of the disease in a young infant. Further research elucidated the role of alkaline phosphatase and the genetic basis of the condition.

Recent Breakthroughs

2015

FDA Approval of Asfotase Alfa

Asfotase alfa, a recombinant TNSALP enzyme replacement therapy, received FDA approval for the treatment of perinatal, infantile, and juvenile-onset hypophosphatasia. This marked a significant advancement in the management of severe HPP, improving survival and skeletal outcomes.

2023

Long-term Outcomes of Asfotase Alfa

Longitudinal studies have demonstrated the sustained efficacy and safety of asfotase alfa in patients with HPP, with improvements in bone mineralization, motor function, and respiratory function observed over several years of treatment.