Hypophosphatasia: Symptoms, Causes, Diagnosis and Treatment

Hypophosphatasia is a rare genetically inherited bone disease. It is characterized by weak bones and teeth because of lack of calcium and phosphate mineralization. Hypophosphatasia is caused due to low level of alkaline phosphatase (ALP) enzyme. This enzyme is extremely important for formation as well as maintenance of healthy bone and teeth.

ALP in a normal person acts as a catalyst and allows easy binding of calcium and phosphate to form healthy bone. But due to ALP deficiency in people suffering from hypophosphatasia, the bone and teeth does not develop properly. This disease can manifest during early infancy or late in adulthood. Patient as a child may present with developmental delays in walking, standing, frequent fractures, premature teeth loss etc. Adult may complain of foot and thigh pain and premature loss of teeth as well as carries. Treatment is symptomatic and supportive in most patients. The main aim is to reduce the morbidity caused from the disease.

Cause of Hypophosphatasia:

Hypophosphatasia is a rare disease. It is a genetically inherited condition. It develops due to mutation in the genes that are involved in producing enzyme alkaline phosphatase(ALP).

The main function of ALP is to bind calcium and phosphate to form strong bone and teeth. In patients with hypophosphatasia, because of defective gene, the level of ALP is very low. Hence the bones and teeth are not strong and healthy. Proper mineralization does not occur. Instead the circulating calcium and phosphorus build up somewhere else in the body such as muscles, kidney, liver, and joints. This will lead to pain and organ damage. The disease is spread from defective gene of parents to the child. Even if one of the parents is having the mutated gene, the child has risk of suffering from hypophosphatasia.

Symptoms of Hypophosphatasia:

The signs and symptoms are varied and may develop during infancy or even adulthood. Usually severe form of this disease occurs before birth or during first few months of life. In perinatal hypophosphatasia, the fetus inside the womb develops non ossified bony spurs on skin. The child after birth has short legs and suffers from frequent seizure and breathing problem. The child survives only for few days after birth. Children and adult having milder form of hypophosphatasia may present with these symptoms:

  • Weak bones leading to frequent stress fractures.
  • Rickets
  • Curved or bow legs.
  • Delayed milestones such as walking
  • Waddling gait
  • Patient is short stature
  • Improper healing of broken bones.
  • Joint and bone pain
  • Early loss of teeth, usually before the age of 5 years.
  • Gum infection
  • Weakness of muscles
  • Joint pain and gout pain due to deposition of calcium in joints.
  • Patient experiences difficulty in walking, standing and has to take assistance of crutches or wheelchair.
  • Frequent breathing difficulty and lung infection due to rachitic chest. The chest silhouette is not well developed as a result, lung do not inflate properly after birth.
  • Small skull size because the bones of skull close early.
  • Seizures in children
  • Kidney damage due to build up of calcium in kidney.

Diagnosis and Treatment:

Hypophosphatasia is caused due to defective gene that regulates the enzyme alkaline phosphatase. It is characterized by weak bones and teeth besides additional symptoms. Diagnosis of the disease is made from the symptoms and alkaline phosphatase blood test. To conform the diagnosis doctors also recommend the patient for genetic testing.

Hypophosphatasia is not curable. The main aim of treatment is to reduce pain and other symptoms that may cause problem in daily life of the patient. Treatment includes:

  • Pain killers
  • Medicines to reduce the incidence of osteoporosis.
  • Reduction of phosphate in diet. It is especially recommended among growth retarded children suffering from hypophosphatasia.
  • Acupuncture, acupressure, massage therapy also helps to alleviate pain and relax the muscles.
  • If fractures fail to heal, surgery may be necessary.

Recently scientists have developed and introduced enzyme replacement therapy. Patients have reported significant improvement. However, further study of the therapy is necessary for its wider application and use.