Hypophosphatasia: literature review and description of a clinical case of familial disease with molecular genetic verification of the diagnosis

Hypophosphatasia is a rare hereditary disease characterized by a very diverse clinical manifestations that can make it difficult to make a timely diagnosis. Due to the deficiency of alkaline phosphatase, multisystem disorders are observed in patients. First of all, these are bone changes (osteoporosis, rickety deformities, fractures), lung damage (hypoplasia with respiratory failure) and central nervous system (seizures), hypercalcemia with the development of nephrocalcinosis. In the absence of timely treatment, the prognosis of the disease in most cases is unfavorable for life. The article describes a family case of hypophosphatasia (GFF) – in a mother and her child. The first clinical symptoms in the child began to manifest at the age of 3 years, the diagnosis of the mother was established at the age of 34 years after the genetic confirmation of the diagnosis in the younger child as a result of examination of the whole family. According to the results of DNA diagnostics (Sanger sequencing), a pathogenic nucleotide variant of C. 595C>T (chr1:21890656C>T) was detected in both family members in a heterozygous state according to the ALPL gene. However, during the molecular genetic studies of Proband's father and sister, no mutations were found. Clinical manifestations were typical for GFF: pain in the lumbar region and in the child, in the knee joints of the mother. The late diagnosis led to the late appointment of substitution therapy. GFF can be suspected based on a combination of clinical symptoms of the disease, characteristic changes according to X-ray examination. For differential diagnosis, it is necessary to determine the activity of alkaline phosphatase. The described case showed that the manifestations of hypophosphatasia are different and differ depending on the age of the manifestation of the disease and the severity of the condition of a particular patient. After genetic verification of the diagnosis, all patients need the appointment of modern enzyme replacement therapy with asphotase alpha, which significantly improves the prognosis of the course of the disease, as well as dispensary observation by specialists of various profiles.

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