Congenital hypophosphatasia is an ultra-rare inborn metabolic defect that is caused by a deficiency in the activity of an important enzyme, alkaline phosphatase, says Jolanta Sykut-Cegielska, MD, IMiD professor, head of the Department of Inborn Metabolic Defects and Pediatrics at the Mother and Child Institute, and national consultant in metabolic pediatrics.
Hypophosphatasia: patients need regular, comprehensive and professional care
Published June 29, 2023 08:00
Hypophosphatasia - what is the disease and what are its symptoms?
J.S.C.: This is an ultra-rare inborn metabolic defect caused by a deficiency of non-specific tissue alkaline phosphatase activity. The deficiency of this enzyme is caused by a gene change. There are various possible variants that are the root cause of this very rare disease. Its symptoms can be extremely varied. Because we have several forms of hypophosphatasia.
The severe form occurs when the child is already sick in the womb, that is, before it is born. In this so-called perinatal form, very severe bone deformities occur, and the child is often stillborn or dies soon after birth.
There is also the infantile form, when symptoms of the disease appear in the first year of life. This can be severe pneumonia associated with abnormal chest structure, but also lung hypoplasia. It has a poor prognosis for the survival of these young patients. And if they survive, they don't function properly and have delayed motor development. They may develop pathological fractures, that is, fractures unrelated to trauma, as early as childhood. Muscle flaccidity is also characteristic; these children are late to start sitting and walking.
In another form, juvenile, the first symptoms occur in older children. And this, too, can be fractures, features of osteopenia or osteoporosis, disorders involving renal function, also kidney stones associated with excessive calcium excretion. Young children may develop vitamin B6-dependent seizures, which is related to the pathomechanism of this disease. There may also be
osteoarthritic pains, which often require either diagnosis or care from rheumatologists. These specialists do not always know or remember that the root cause of these symptoms may be an inborn defect of metabolism, specifically just hypophosphatasia.
What is the current care for these patients? What are their most pressing needs?
J.S.C.: The patients are both children and adults. There are no reference centers dedicated to hypophosphatasia in Poland, but we have quite a few different centers specializing in rare diseases, and that's where these patients should go. Unfortunately, to my knowledge, this is not happening. They end up in different facilities, depending on which specialist takes care of them. For the time being, we can offer them care consisting of monitoring the course of the disease and symptomatic treatment, mainly pain relief and - if necessary - orthopedic or surgical treatment. I hope that the Ministry of Health will soon make available enzyme treatment, which is reimbursed in Poland under drug programs for other diseases. Then the situation should change. Patients would have full care and would be well monitored. I think there will soon be a chance for just such care for these patients. Because this is what they need: regular, comprehensive and professional.
What number of patients with hypophosphatasia in Poland can we currently talk about?
J.S.C.: There is not yet a nationwide registry of these patients. One can only talk about databases in places where there are more such patients. In our center, the Mother and Child Institute, we currently have 4 patients under our care, of which only one is a child. On the other hand, according to the HypoGenek Foundation, which takes care of patients with this disease only, there are about 20 of them. However, I think there are many more, only some people have not yet been diagnosed.
