hypophosphatasia, autosomal recessive
What is Hypophosphatasia, Autosomal Recessive?
Hypophosphatasia is an inherited disorder that disrupts a process called mineralization, in which the body deposits minerals like calcium and phosphorus into teeth and bones. Proper mineralization is necessary to make bones strong and rigid, and make teeth strong enough to withstand years of chewing.
Hypophosphatasia can have two types of inheritance patterns: autosomal recessive (symptoms are seen when both disease genes have mutations) or autosomal dominant (symptoms occur when only one of two disease genes has a mutation). With autosomal recessive hypophosphatasia, symptoms can vary greatly depending upon which mutations a person carries. Some forms of the disease are severe while other forms are extremely mild.
The most severe form of hypophosphatasia appears before birth or in early childhood. In many cases, infants are stillborn because their skeletons fail to form. Other affected infants are born with short limbs, soft skull bones, and an abnormally shaped chest caused by soft, weak ribs. Approximately half the infants born with the condition die of respiratory failure in the first few weeks of life. Those who survive may have life-threatening complications such as breathing problems, seizures, or high blood calcium levels leading to kidney damage.
In a less severe form, children show the first signs of the condition by losing their baby teeth before the age of five. As they grow, they may be below average in height, with bowed legs or knock knees, large wrist and ankle joints, and an abnormally shaped skull. They are more prone to broken bones, bone pain, and arthritis. They may have trouble learning to walk or may develop a waddling gait. Their teeth may crack or decay more easily than normal.
The mildest form of the disorder is called odontohypophosphatasia. It only affects the teeth. People with this form of the condition have abnormal tooth development and lose their teeth early, but do not have skeletal abnormalities.
Occasionally, people with hypophosphatasia do not develop any symptoms until middle age. The most common symptoms are early tooth loss and frequent, slow-healing stress fractures in the feet. They may also develop arthritis.
How common is Hypophosphatasia, Autosomal Recessive?
Hypophosphatasia affects approximately 1 in 100,000 people and is most common in Caucasians. The disease is particularly common in a particular Mennonite population in Ontario, Canada, where it affects 1 in 2,500 people.
How is Hypophosphatasia, Autosomal Recessive treated?
Infants with the most severe form of the condition usually require mechanical help to breathe and may need surgery to release pressure within the skull. Vitamin B6 may relieve seizures.
Children and adults with hypophosphatasia should see a dentist every year, beginning at the age of one, to preserve teeth as long as possible. Adults will eventually need false teeth.
Aspirin, ibuprofen, and other pain relievers help with bone pain and arthritis. Although preventing bone fractures is difficult, orthotics may help with common fractures in the feet.
People with the condition should not take bisphosphonates, which are drugs commonly prescribed to treat other bone loss conditions such as osteoporosis. They should also avoid excess vitamin D, which can make calcium build up in the blood.
What is the prognosis for a person with Hypophosphatasia, Autosomal Recessive?
Approximately 50% of infants born with the severe form of the condition will die of respiratory failure in infancy. Exact lifespan for the rest is not known. People with the milder forms of the condition have normal lifespans.