Hypophosphatasia (HPP) is a rare inherited genetic metabolic disorder affecting mineralization of bones and teeth. It is a progressive disorder caused by mutation of ALPL gene. The severity of the disease may vary widely from frequent fractures to fetal death. This disease can be present in anyone from infants to adults.
Signs and symptoms of hypophosphatasia include poor feeding in infants, weak bones and teeth, short stature, and various other skeletal abnormalities. Most cases of hypophosphatasia may have history of early loss of primary teeth due to defective calcification. Hypophosphatasia is classified into 5 clinical forms such as perinatal, infantile, childhood, adult, and odonto.
There is no medicine that can treat hypophosphatasia, the aim of management is to alleviate symptoms, reduce complications and improve overall quality of life. Recently enzyme replacement therapy (ERT) has shown promising results in resolving bone problems especially in childhood form of hypophosphatasia.
What Is The Cause Of Hypophosphatasia?
Hypophosphatasia is a rare genetic inherited disorder. It occurs in 1 out of 100000 live births. The disorder is caused by mutation of ALPL gene. This gene is responsible in giving instruction to produce an enzyme called alkaline phosphatase. Alkaline phosphatase plays and active role in mineralization of bones and teeth.Mutation in the ALPL gene leads to production of abnormal version of alkaline phosphatase. This affects proper mineralization hence the bone and teeth become weak.
Calcium and phosphate that are needed for strong bones and teeth circulate in the system without getting deposited in bones because of lack of or complete absence of enzyme alkaline phosphate. The accumulated minerals now start depositing in other parts of body such as the brain, lungs, kidney, joint and muscles causing damage to these organs.
In case of perinatal and infantile hypophosphatasia, mutation occurs in both copies of genes in the cell. Thus it develops as a severe form of hypophosphatasia as there is complete absence of alkaline phosphatase enzyme activity. In milder forms, a mutation takes place only in one copy of gene hence it reduces the activity of alkaline phosphate enzyme, but does not eliminate it completely. Perinatal and infantile are severe form whereas childhood, adult and odonto are milder variety of hypophosphatasia.
Signs And Symptoms Of Hypophosphatasia
There are variety of signs and symptoms of hypophosphatasia. They may develop during perinatal stage, infancy or in adulthood. The severe form of hypophosphatasia occurs before birth of the child or during infancy. Perinatal type is lethal and most pregnancies end in stillbirth.
Perinatal: Severe form of hypophosphatasia.
- Detected when the fetus is in womb.
- Ultrasound examination detection.
- Small chest cavity
- Short limbs
- Bowed limbs.
- Incomplete development of lungs.
- Symptoms manifest between birth and six months.
- Weak and soft bones.
- Small sized chest.
- It leads to respiratory problems.
- Increased irritability due to accumulation of calcium in circulation.
- Poor feeding
- Loss of muscle tone.
- Dehydration due to frequent urination.
- Renal damage
- Premature loss of primary teeth.
- Skeletal deformities.
- Delayed milestones such as walking, standing etc.
- Short stature with bowed legs.
- Enlarged ankle and knee joints.
- Abnormal shape of skull.
- Frequent stress fractures are the cardinal feature. It occurs in foot and thigh bones.
- Symptoms usually develop in middle age.
- Foot pain, thigh and pain in hips.
- Early loss of secondary teeth with other dental problems.
- Softening of bones called osteomalacia.
- Painful joints
- It is the mildest of all types of hypophosphatasia, only affecting teeth.
- Early loss of primary teeth.
- There is no skeletal deformity.
Treatment Options For Hypophosphatasia
Diagnosis of hypophosphatasia is made on clinical of signs and symptoms as well as medical history. Besides, various blood tests including level of alkaline phosphate in serum and X-ray of bones will help to determine the disorder.
There is no particular medicine that will be effective in curing hypophosphatasia. However, the management is aimed at addressing and alleviating the symptoms and preventing complication. The purpose is to make daily life of the patient easier to live.
- Patient may need to restrict intake of calcium and vitamin D.
- Infants may need supportive ventilation due to respiratory problems.
- Analgesic to alleviate pain.
- Acupressure and acupuncture, massage therapy. Care is taken not to put more pressure on weak bones.
- Relaxation techniques such as meditation and yoga.
- Surgery for fractures that does not heal.
- Enzyme replacement therapy has been recently introduced. It is beneficial in bone problems in infantile and childhood onset hypophosphatasia.