Neuropathic forms of lisosomal storage diseases in Ukraine


  • N.O. Pichkur Orphan’s Diseases Center, National Specialized Children Hospital “Okhmatdyt”, Kyiv, Ukraine Shupik National Medical Academy of Postgraduate Education, Kyiv, Ukraine



lysosomal storage diseases, neuropathic forms, sphingolipidosis, mucopolysaccharidosis, neuronal ceroid lipofuscinosis, metachromatic leukodystrophy, biochemical, molecular and genetic diagnosis


Background. To date, several thousands of hereditary diseases have been detected, characterized by the defeat of the nervous system. These include lysosomal storage diseases (LSD). Lysosomal storage desiaeses — is a large group of monogenic metabolic disorders (about 60), inherited mainly by the autosomal recessive type; most of them — are serious diseases with progressive flow that cause severe disability and early death of the patients. LSD are characterized by accumulation of enzymes substrates or products of their incomplete degradation and segregated cytoplasmic components, etc. in different cells and tissues and it causes many disorders. Depending on the accumulated substrate nature, the following LSD are distinguished: mucopolysaccharidosis, sphingolipidosis, mucolipidosis, oligosaccharidosis, etc. Certain LSD clinical flow depends on the pathological process type and location, accumulated biochemical substrate nature, and is usually multisymptomatic. Within one nosological form various phenotypes are found: from «soft» to severe; first symptoms of the disease may be nonspecific, reminiscent of other, more common diseases. Most LSD require complex stage-by-stage clinical and laboratory diagnostics. Until recently almost all LSD considered as incurable; specific correction methods were successfully developed and introduced into medical — it has become one of the most significant achievements in a worldwide medical science of recent decades. Recently, significantly expanded range of LSD laboratory diagnostics gained unique experience in clinical identification of their various forms that significantly influenced on the disease incidence revealing, allowed to analyze epidemiological indicators, to develop effective measures for early diagnosis optimization. The purpose of the study was to study the prevalence and spectrum of neuropathic forms of lysosomal accumulation diseases in Ukraine, comparing the results with epidemiological studies conducted in other countries. Materials and methods. LSD enzyme diagnostics in Ukraine is used since 1995: today it is possible to determine the activity of 25 enzymes in homozygous leukocytes, blood plasma, chorionic biopsy, skin fibroblasts cells culture that allowed to verify 30 different diseases. Each LSD has its own biochemical characteristics. The laboratory diagnostics success depends on a clear definition of a clinical problem. This approach is a key to correct diagnosis, further clinical and laboratory monitoring during LSD treatment. Data of the complex clinical and laboratory examination of patients with different forms of LSD provided in the National Specializes Children Hospital «Okhmatdit» in the period 1995–2016 have been analyzed. For LSD laboratory diagnostics we selected patients with multisymptomatic clinical picture which were grouped on the basis of certain organs and systems disorders; for each group phase-based research protocols were used. Results. The diagnosis of lysosomal disease was established in 343 patients from 324 families from all regions of Ukraine. The most numerous group in the structure of lysosomal diseases revealed sphingolipidosis (52 % of cases) and mucopolysaccharidosis (30 %). Neuropathic variants were diagnosed in 84 (47 %) of 179 patients from the sphingolipidosis group. We diagnosed Gaucher disease in 19.4 % of patients. The second type of Gauchers disease (acute neuropathic form) was detected in 3 (5 %) patients, type III in 5 (8 %). The most numerous in LSD structure were sphingolipidosis (52 %) and mucopolysaccharidosis (30 %); a significant place took GM1-gangliosidosis (8 %) and metachromatic leukodystrophy (7 %). According to our research, LSD structure in Ukraine is similar to other European countries, but in the same time the incidence of Gaucher and Fabry disease, metachromatic leukodystrophy, mucopolysaccharidosis type I was lower, probably due to LSD significant clinical polymorphism and a large number of adult patients. Conclusions. In the future we are planning to study LSD prevalence in Ukraine, to analyze the mistakes in their late diagnostics in order to develop and implement in the medical practice effective early diagnostic algorithms for certain forms of LSD, for which there are effective methods of treatment.


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Original Researches