Causes and Symptoms of Hypophosphatasia
Hypophosphatasia Treatment is a rare genetic disorder caused by mutations in the gene that codes for the enzyme alkaline phosphatase. This enzyme plays a key role in mineralization of bones and teeth. Due to the deficiency of this enzyme, minerals like calcium and phosphate cannot be properly incorporated into the bones and teeth during their development and growth. The signs and symptoms of hypophosphatasia vary depending on the severity and type but may include softened or deformity of bones, delayed teeth development, seizures or breathing problems. There are various clinical forms of hypophosphatasia based on the age of onset and severity of symptoms.
Diagnosis of Hypophosphatasia
The diagnosis of hypophosphatasia is usually made based on clinical signs and symptoms, family history, and laboratory tests. A blood test is done to measure the level of alkaline phosphatase in the blood which will be low in patients with hypophosphatasia. A genetic test may also be performed to identify any mutations in the ALPL gene. Bone mineral density scans like DXA can detect low bone mineralization. In infants, a laboratory test of urine for elevated levels of a bone marker called pyridoxal 5′-phosphate is also indicative of hypophosphatasia. Radiographs and MRI scans are helpful for assessing any abnormalities in bones and teeth. Prenatal diagnosis through ultrasonography, biochemical tests and molecular analysis of fetal DNA is possible if family history of condition is known.
Enzyme Replacement Therapy
Currently, the only approved Hypophosphatasia Treatment is enzyme replacement therapy with the drug asfotase alfa, marketed under the brand name Strensiq. It is a form of bone-targeted alkaline phosphatase designed to supplement the missing or deficient alkaline phosphatase enzyme in patients. Asfotase alfa is administered through intravenous infusions 2-3 times per week. Clinical trials have shown it to be effective in improving skeletal mineralization and healing of fractures in children and adults with hypophosphatasia. However, enzyme replacement therapy needs to be continued lifelong as discontinuation can result in loss of treatment effect and reemergence of symptoms. It is generally well-tolerated but some common side effects observed are pyrexia, headache, nausea, vomiting, etc.
Physical Therapy and Orthopedic Procedures
In addition to enzyme replacement therapy, physical therapy plays an important supportive role in hypophosphatasia treatment. Physiotherapy aims to improve muscle strength, mobility and prevent complications from fractures or skeletal deformities. Occupational therapy can assist patients in performing daily activities and improve their quality of life. Surgical procedures like skeletal stabilization using pins or braces may be required in cases with severe fractures or bowing of legs. Dental procedures may be needed for management of dental abnormalities, placement of braces or dentures. Nutritional support with adequate calcium and vitamin D supplements is also recommended.
Bone Marrow or Umbilical Cord Transplantation
In severe forms that do not respond adequately to enzyme replacement therapy, bone marrow or umbilical cord blood transplantation may be considered. It involves transplanting hematopoietic stem cells from a healthy donor into a patient with hypophosphatasia. The donor cells would then produce the missing alkaline phosphatase enzyme in various tissues. However, this is a high-risk procedure with serious potential complications and long-term immunosuppression. It has shown some benefit in a few reported cases but is generally reserved only for patients with life-threatening manifestations. More research is still needed regarding the effectiveness and safety of hematopoietic stem cell transplant for different types of hypophosphatasia.
Genetic Counseling and Prenatal Diagnosis
As hypophosphatasia is inherited in an autosomal recessive pattern, genetic counseling helps affected individuals and families understand the risk of having another child with the condition. Carrier testing and prenatal diagnosis options are discussed. Prenatal diagnosis by analyzing fetal cells obtained through amniocentesis or chorionic villus sampling can determine if the fetus is affected. Identification of mutations in both parents also allows determination of risk in future pregnancies. Prenatal diagnosis allows families at high risk to be prepared for intensive neonatal management if fetus is affected.
Summary
In summary, enzyme replacement therapy with asfotase alfa remains the mainstay of hypophosphatasia treatment. Early initiation leads to better outcomes. However, lifelong therapy is required. Supportive measures involving physical/occupational therapy, orthopedic interventions and nutritional supplements complement medical management. In very severe cases, hematopoietic stem cell transplant may provide benefits but requires further research. Genetic counseling and prenatal testing help families understand risks and options for future pregnancies. With advances in understanding pathogenesis and management, outcomes continue improving for individuals with this rare genetic condition.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it