Endocrine Abstracts

Introduction: Hypophosphatasia is a group of inherited disorders characterized by the impaired mineralization of bones and/or teeth and low serum alkaline phosphatase (ALP) activity. It is caused by a mutation in the ALPL gene encoding the isoenzyme of ALP resulting in a loss of function. Since an early age of onset is usually associated with a more severe disease, and a late age – with a mild course of the disease, the manifestation of the disorder ranges from a life-threatening condition occurring at birth, characterized by severely impaired bone mineralization and seizures, to young adults with premature tooth loss without other symptoms. Relatively little data is available on the prevalence and clinical features of hypophosphatasia in adults.

Clinical case: An 18-year-old female (weight 56 kg, height 160 cm, BMI 21.9) with complaints of weakness, pain in the legs and joints, darkening in the eyes. Development in childhood and adolescence proceeded without any special features. Considers herself sick since the age of 16, when swelling and tenderness of the left ankle and knee joints appeared without x-ray changes. At the same time, the patient was diagnosed with infectious mononucleosis, after which she noted an increase in general weakness, periodic increases in body temperature to 37.2 0C, loss of appetite, pain in the bones and joints. CRP, ASLO, RF – negative, biochemical indicators, parameters of bone and calcium-phosphorus metabolism were normal except for the detected decrease in ALP to 13-15 U/l (40-150) and a pronounced deficiency of vitamin D - 9 ng/ml (30-100). The diagnosis of hypophosphatasia was confirmed: a pathogenic nucleotide variant chr1:21563115C>A was detected in a heterozygous state in the ALPL gene. According to DEXA of the whole body, BMD, taking into account the skull, corresponds to the age norm: -0.5 SD (Z-criterion);BMD excluding the skull corresponds to the age norm: -0.7 SD. According to lateral morphometry, no data were obtained for vertebral deformities and compression fractures. Teeth, hair, nails without any features. A detailed collection of family history revealed similar symptoms of joint pain in the mother with a decrease in ALP to 20 U/l (35-105).

Conclusions: Despite low ALP activity the patient does not demonstrate the typical clinical indications of hypophosphatasia, as evidenced by the absence of manifestations in the mother. The observed symptoms could possibly be the result of mononucleosis. Other genetic, epigenetic, or non-genetic factors influencing illness progression may explain circumstances where it is difficult to demonstrate a link between a pathology’s genotype and phenotype.