Hypophosphatasia (HPP, Hypophosphatemia, Hereditary Hypophosphatemia,)


What Is Hypophosphatasia?

What is Hypophosphatasia?

Hypophosphatasia(HPP), also known as hypophosphatemia and hereditary hypophosphatemia, is a rare hereditary systemic disease. It is characterized by dysplasia of the hard tissues of the bones and teeth and low serum alkaline phosphatase activity.

At present, the etiology and pathogenesis of Hypophosphatasia are unknown, and there is no thorough treatment.

Is Hypophosphatasia common?

HPP patients can be seen in all ethnic groups worldwide, but the prevalence varies widely in different regions. Canada had the highest prevalence and the prevalence of severe HPP was approximately 1:100,000.

It is difficult to accurately assess the prevalence of benign HPP in patients due to differences in clinical presentation and the presence of a large number of undiagnosed patients.


What Is Cause Of Hypophosphatasia?

Why is Hypophosphatasia causing bone defects?

The alkaline phosphatase ALPL genome on chromosome 1p36.1 encodes non-tissue-specific alkaline phosphatase, which is biologically active in the form of dimer and can hydrolyze phosphate metabolic substrates in extracellular matrix to separate inorganic phosphorus and promote the formation of mineralized crystals. The enzyme activity is decreased due to gene mutation, resulting in bone and tooth development defects and mineralization abnormalities.

Is Hypophosphatasia contagious?

Hypophosphatasia is a hereditary disease that is not contagious.

Is Hypophosphatasia hereditary?

Hypophosphatasia is a rare autosomal inherited disorder that can be either dominant or recessive.


What Are The Symptoms Of Hypophosphatasia?

Why is Hypophosphatasia causing bone defects?

What are the types of Hypophosphatasia?

  • Perinatal Death: Fatal at this time, usually occurring in the fetal stage, with marked bone mineralization and prominent skin-covered spurs in the forearm or leg. Children often die during the perinatal period, with some surviving for days after birth but with severe respiratory complications due to thoracic deformity caused by dysplasia of lung tissue and rickets.
  • Benign perinatal period: fetal presentation but spontaneous improvement of bone defects on ultrasound, with short, curved limbs and long depressed bones.
  • Infant: normal performance at birth, symptoms within six months after birth, respiratory complications caused by rickets thoracic deformity, intracranial hypertension often due to premature closure of cranial sutures, hypercalcemia, increased urine calcium and renal calcium deposition. Infants may cry, lack of appetite, vomiting, polyuria, constipation, hypotonia and other symptoms. High excretion of calcium can cause renal damage, and surviving children can show improved mineralization and symptom relief.
  • Children: Symptoms six months after birth, the most complex type, intracranial hypertension and growth retardation, typical symptoms, skeletal malformations, enlarged joints, short stature, and a faltering gait. Fractures and bone pain are common, with local bone defects at both ends of the long bone. Premature loss of teeth, often occurring first in the incisors, may spontaneously resolve bone defects, but skeletal symptoms may recur in adulthood.
  • Adults: Symptoms usually occur in middle age and are usually noticed because of pain in the foot or leg caused by fractures of the metatarsal or femur. Chondrocalcinosis and osteoarthropathy are also common. Many patients also have a history of premature deciduous tooth loss. Some patients may also have kidney calculi, kidney dysfunction and insomnia, anxiety, depression and other mental symptoms.
  • Teeth: Can occur in children as well as adults, with typical symptoms of premature deciduous tooth loss and severe caries, usually without systemic skeletal dysplasia. The X-ray shows that the alveolar bone is insufficient, and the medullary cavity and root canal are thick.

How To Check For Hypophosphatasia?

How to diagnose whether you have Hypophosphatasia?

The diagnosis of HPP is mainly based on clinical manifestations, physical examination, laboratory examinations, and X-ray examinations. Genotype analysis and detection of ALPL gene mutations have diagnostic value for suspected cases.

What are the tests required of Hypophosphatasia?

  • Blood biochemical tests: HPP should be highly suspected for decreased serum ALP activity, but the severity of HPP may not be proportional to the degree of decreased ALP with age. However, it should be noted that the decrease in ALP activity may also occur in other diseases, such as early pregnancy, hypothyroidism, celiac disease, malnutrition, anemia, etc.
  • Genetic testing: ALPL gene analysis will be an important method for the diagnosis of HPP, especially when the clinical manifestations and laboratory tests fail to confirm the diagnosis in pregnant women who have given birth to HPP infants in the past. Screening for mutational sites is a more reliable indicator than detection of serum ALP activity, but attention should also be paid to the occurrence of certain new mutation types.
  • X-ray: X-ray examination evaluates the severity of bone mineral insufficiency and rickets. Abnormalities of leg bones can be found, such as bone spurs and short bones.
  • Bone densitometry: There is little evidence that bone mineral density contributes to the diagnosis of HPP.
  • Histopathological examination: Bone histological examinations of almost all the patients except for dental HPP showed insufficient mineralization and microstructural changes in bone trabeculae. Osteoblasts and chondrocytes which produced TNSLP were present, but the activity of TNSLP was still significantly decreased or even completely disappeared.

Which illnesses are easily confused with Hypophosphatasia?

Hypophosphatasia is often associated with oral manifestations, including periodontitis and caries in dental tissue. This disease should be considered in any patient with a history of spontaneous tooth loss and abnormal loosening during oral examinations.


How To Prevent Hypophosphatasia?

Can Hypophosphatasia be prevented?

Genetic analysis of Hypophosphatasia is difficult to perform because it may be autosomal dominant or recessive and clinical presentations are diverse in heterozygous patients. Affected by genetic polymorphisms, mutations or polymorphisms in other genes can affect phenotypes. The investigation of the family lineage is important. However, there has been no definitive study showing that prenatal diagnosis contributes to the screening or prevention of HPP.


How To Treat Hypophosphatasia?

Hypophosphatasia is a hereditary disease, and it needs to go to the pediatrics for treatment when it occurs in children or infants. There is currently no cure for Hypophosphatasia, most of which are based on symptoms.

General treatment:

  • Oral care includes removal of excessively loose teeth, maintenance of oral hygiene and, in some areas, periodontal surgery.
  • Growth hormone replacement therapy promotes bone growth and increases alkaline phosphatase activity.
  • Long-term supplementation with vitamin D and calcium may help.
  • Phosphate limits in the diet.
  • Non-steroidal anti-inflammatory drugs, bone marrow and mesenchymal stem cell transplantation can be used in pain to improve bone mineralization.

Bone marrow transplantation: Some patients with infantile HPP may see obvious benefits after bone marrow transplantation.

In addition, enzyme replacement therapy of TNAP recombinant protein is still in the research stage.


What Should Hypophosphatasia Patients Pay Attention To In Life?

Can Hypophosphatasia be cured?

For different types, the prognosis varies greatly. Perinatal patients usually die within a few days or weeks after birth, and 50% of infant patients die from severe respiratory complications. Pediatric patients have much difference, and adults and dental types do not affect life span.

Will there be sequelae after the treatment of Hypophosphatasia?

Hypophosphatasia can have decaying, loose teeth, and often fractures of the metatarsal or femur that cause pain in the foot or leg.

How long does Hypophosphatasia need to be treated?

Hypophosphatasia is a hereditary disease, and there is no complete treatment method. The treatment is mostly symptomatic treatment, which is lifetime.

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