Прогрессирующая мышечная дистрофия Дюшенна (ПМД Дюшенна) является наиболее распространенным нервно-мышечным заболеванием в мире. ПМД Дюшенна относится к группе так называемых дистрофинопатий, связанных с мутациями в гене DMD, наследуется по Х-сцепленному рецессивному типу и обусловлена либо полным отсутствием белка дистрофина, либо его дефектным синтезом. В настоящее время появилось несколько патогенетических лекарственных препаратов, направленных на восстановление синтеза белка дистрофина. Одним из них является антисмысловой олигонуклеотид касимерсен, работающий по технологии экзон-скиппинга 45 экзона. В статье представлен первый опыт применения препарата касимерсен у 6 пациентов из России, причем пациенты значимо отличались друг от друга по функциональному статусу и имеющимся осложнениям основного заболевания. У всех пациентов применение касимерсена было безопасным, не было выявлено никаких нежелательных явлений, связанных с применением препарата. А у одного из пациентов, находящегося на ранней амбулаторной стадии болезни, которому патогенетическая терапия была инициирована в возрасте 7 лет, констатирована выраженная положительная динамика в виде прироста дистанции на 140 метров по результатам 6-минутного теста ходьбы и увеличения на 10 баллов по шкале «Северная Звезда». Duchenne muscular dystrophy (DMD) is the most common neuromuscular disease in the world. DMD belongs to the group of so-called dystrophinopathies associated with mutations in the DMD gene, is inherited in an X-linked recessive manner and is caused by either the complete absence of the dystrophin protein or its defective synthesis. Currently, several pathogenetic drugs have appeared aimed at restoring the synthesis of the dystrophin protein. One of them is the antisense oligonucleotide casimersen, which works using exon skipping technology of exon 45 in DMD gene. The article presents the first experience of using the drug casimersen in 6 patients from Russia, and the patients differed significantly from each other in functional status and existing complications of the underlying disease. In all patients, the use of casimersen was safe, and no adverse events associated with the use of the drug were identified. And in one of the patients, who was at an early outpatient stage of the disease, for whom pathogenetic therapy was initiated at the age of 7 years, pronounced positive dynamics were noted in the form of an increase in distance by 140 meters according to the results of a 6-minute walking test and an increase of 10 points on the «North Star».

Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disease due to a mutation in the gene encoding dystrophin synthesis. In patients, muscle damage and atrophy progresses, the ability to move independently decreases as well as respiratory and cardiac functions. At various stages of the disease, different methods of care and treatment of patients with DMD are used. The clinical effect of new methods of DMD target therapy may depend on the stage of development of the disease (ambulatory or non‑ambulatory). To date, there are no unified criteria for assessing the status of a patient in terms ambulatory. In clinical trials and real clinical practice, different approaches are used to assess the patient’s status. However, the conclusion about the functional capabilities is critical for patients with DMD as approaches in management of patients in ambulatory and non‑ambulatory stages differ significantly. This necessitates expert consensus to achieve consistency and avoid any of discrepancies on that issue.The paper reviews the available published data on the concepts of “ambulatory” and “non‑ambulatory” used in clinical trials, real clinical practice, international standards and recommendations. As a conclusion of this analysis, it is proposed in real clinical practice to interpret “ambulation” in DMD patients as ability to walk without the use of assistive devices and without specifying the distance and time, and “non‑ambulation” as condition in which the patient is forced to constantly use a wheelchair both indoors and outdoors.

Background. Glutaric aciduria type 1 is an autosomal recessive disease caused by mutations in the GCDH gene, which encodes the enzyme glutaryl‑CoA dehydrogenase. Metabolic crisis in type 1 glutaric aciduria is an acute life‑threatening condition that requires careful diagnosis with a number of other conditions and the immediate initiation of pathogenetic therapy.Materials and methods. Clinical manifestations, neuroimaging characteristics of the disease were studied in 46 patients with diagnosed glutaric aciduria type 1 confirmed by biochemical and molecular genetic methods. Methods: gas chromatography with mass spectrometry, tandem mass spectrometry, Sanger sequencing, chromosomal microarray analysis of the exon level.Results and discussion. A retrospective analysis of anamnestic and clinical data was carried out, and the nature and age of disease manifestation, provoking factors, a spectrum of clinical manifestations and neuroimaging data were assessed.Conclusion. How initiated treatment prevents progression of neurological symptom relief and patient adaptation. With the help of the goal, it is necessary to inform pediatricians, neurologists and neuroradiologists about this feature of the course of glutaric aciduria type 1 in order to increase the clinical alertness of this disease.

Болезнь Краббе (БКр) - редкое наследственное аутосомно-рецессивное заболевание, входящее в группу лизосомных болезней накопления. Заболевание обусловлено мутациями в гене GALC, приводящими к дефициту фермента галактозилцерамидазы. Частота БКр оценивается как 1:100 000 живых новорожденных, хотя в некоторых странах регистрируется более высокая частота заболевания. Точная частота БКр в Российской Федерации и в ее регионах неизвестна. Мажорной мутацией, приводящей к развитию БКр, является крупная делеция затрагивающая 11-17 экзоны гена GALC c.1161+6532_polyA+9kbdel (IVS10del30kb). Доля этой мутации в европейской популяции оценивается примерно в 50% от всех мутаций. Для изучения спектра и частот мутаций гена GALC на территории РФ были обследованы пациенты из разных регионов. Частая делеция составила 54% от общего числа выявленных мутаций, что сопоставимо с данными по европейской популяции. Однако в Чеченской Республике данная мутация встречалась гораздо чаще, чем в других регионах. Среди 950 исследованных образцов было выявлено 7 гетерозиготных носителей частой мутации. Учитывая вклад других мутаций, расчётная частота БКр в республике составила 1:51237, что превышает таковую в европейской популяции. Дополнительный анализ всех найденных мутаций гена GALC позволил выявить вариант c.578T>C, p.Ile193Thr, аллельная частота которого составила 8%. Данная замена впервые была описана у пациентов из нашей выборки и встречается только при поздней инфантильной форме заболевания у русских пациентов. Krabbe’s disease (KD) is a rare inherited autosomal recessive lysosomal storage disease. KD is caused by mutations in the GALC gene leading to deficiency of galactosylceramidase. KD oссurs in 1 per 100 000 newborns, although some countries have a higher incidence rate. The exact KD incidence in Russia is unknown. A major mutation leading to the KD development is a large deletion affecting exons 11-17 of the GALC gene с.1161+6532_polyA+9kbdel (IVS10del30kb). This mutation occurs in 50% of KD cases in the European population. Patients from different regions were studied to analyze the mutation spectrum and the incidence in the Russian population. The incidence rate of the large deletion in our study equals 54%, that is comparable with European population. However, in the Chechen Republic this mutation is much more common than in other regions. 950 samples were studied, 7 heterozygous carriers of frequent mutation were identified. Thus, the estimated KD incidence rate is 1:51237 considering other mutations, and it is higher than that in the European population. Additional analysis of all detected GALC mutations revealed a genetic variant c.578T>C, p.Ile193Thr with allelic frequency measured up 8%. This substitution was described in our selection for the first time and presented only in Russian patients with late infantile form of the disease.

Пропионовая ацидемия (ПА) - редкое наследственное заболевание с аутосомно-рецессивным типом наследования, относится к «классическим», т.е. наиболее часто диагностируемым органическим ацидемиям. В данной работе представлена биохимическая и молекулярно-генетическая характеристика 16 пациентов с ПА, выявленных в Российской Федерации. У большинства обследованных пациентов первые симптомы проявились в первые месяцы жизни, наиболее частые из них: нарушения вскармливания, судороги, мышечная гипотония, угнетение сознания. При биохимическом исследовании (ГХ-МС и МС/МС) у пациентов было выявлено повышение концентрации 3-гидроксипропионой кислоты, метилцитрата, пропионилглицина, C3, глицина, которые являются патогномоничными маркерами этой патологии. В результате молекулярно-генетического анализа в генах PCCA и PCCB было выявлено 6 неописанных ранее вариантов нуклеотидной последовательности (4 варианта в гене PCCA, 2 - в гене PCCB), один из которых (PCCB: c.655-2A>G) имеет высокую частоту (17,2%, 5/29 мутантных аллелей генов PCCA и PCCB) в исследуемой выборке. Локализация миссенс-вариантов и их влияние на структуру белка были продемонстрированы на 3D-модели фермента пропионил-КоА-карбоксилазы. Выявленным вариантам были присвоены критерии патогенности в соответствии с рекомендациями American College of Medical Genetics and Genomics (ACMG). Propionic acidemia is a rare autosomal recessive metabolic disorder, characterized as classic organic acidemia. The article represents biochemical and molecular characterization of 16 patients diagnosed with propionic acidemia in Russia. Symptoms appeared during the first months after birth in most cases. Poor feeding, seizures, hypotonia, lethargy were the most frequent symptoms. Biochemical tests (GC-MS and MS/MS) showed elevated 3-hydroxypropionic acid, methylcitrate, propionylglycine, C3 in patients blood. Six undescribed earlier variants were found as a result of PCCA & PCCB (4 variants - PCCA, 2 - PCCB) genes DNA-tests. Variant c.655-2A>G in PCCB is the most frequent in this group (17.2%). Localization of missense variants and their effect on protein was demonstrated using propionyl-CoA carboxylase 3D model. New variants were classified according to the American College of Medical Genetics and Genomics (ACMG) guidelines.

Treatment of many of the diseases in the panel of expanded newborn screening includes dietary therapy. Glutaric aciduria type 1 (GA1) is a hereditary disorder caused by mutations in the gene GCDH, encoding glutaryl‑CoA dehydrogenase, an enzyme in the amino acid metabolic pathways. The decreased activity of the enzyme leads to accumulation of neuro‑ toxic metabolites. The recommended treatment approaches for GA1 are the prescription of specialized nutrition products, levocarnitine, and symptomatic management. In 2021, clinical guidelines for the treatment of this rear disease were published in Russian Federation. To provide for the timely treatment, it is essential for a practitioner involved in the care patients with such a rare disorder as GA1 to have the knowledge of the principles of management, as well as practical algorithms for diet calculation.The article gives a detailed case‑based description of management during metabolic decompensation and the choice of dietary therapy for GA1 patients of different age groups.

Mucopolysaccharidosis I-Hurler (MPS I-H) is the most severe form of a metabolic genetic disease caused by mutations of IDUA gene encoding the lysosomal α-L-iduronidase enzyme. MPS I-H is a rare, life-threatening disease, evolving in multisystem morbidity including progressive neurological disease, upper airway obstruction, skeletal deformity and cardiomyopathy. Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the gold standard for the treatment of MPS I-H in patients diagnosed and treated before 2–2.5 years of age, having a high rate of success. Enzyme replacement therapy (ERT) with human recombinant laronidase has also been demonstrated to be effective in ameliorating the clinical conditions of pre-transplant MPS I-H patients and in improving HSCT outcome, by peri-transplant co-administration. Nevertheless the long-term clinical outcome even after successful HSCT varies considerably, with a persisting residual disease burden. This review will focus on all these critical issues related to the management of MPS I-H.

Введение. Дефицит лизосомной кислой липазы (ДЛКЛ) - континуум аутосомно-рецессивно наследуемых фенотипов, обусловленных генетическими дефектами фермента лизосомной кислой липазы (ЛКЛ), играющего ключевую роль в обмене липидов. ЛКЛ кодируется геном LIPA, наиболее распространенный патогенный вариант которого -c.894G>A - является причиной заболевания в более чем половине случаев. Точная частота ДЛКЛ неизвестна, в России она предположительно составляет от 1:150 000 до 1:100 000 новорожденных. Цель: биохимический скрининг на ДЛКЛ в группе высокого риска, изучение спектра мутаций гена LIPA и оценка встречаемости заболевания в г. Москве. Методы. В исследовании участвовали 1999 пациентов из различных регионов РФ с подозрением на лизосомные болезни накопления (ЛБН). Выборку для исследования носительства частого варианта гена LIPA составили сухие пятна крови 920 живых новорожденных г. Москвы. Активность ЛКЛ измерялась флуориметрическим методом в сухих пятнах крови. Кодирующая последовательность гена LIPA изучалась путём прямого секвенирования и ПДРФ-анализа. Результаты. Тридцати четырем пациентам установлен диагноз ДЛКЛ. Выявлено 16 вариантов гена LIPA, из них 11 не описаны ранее. Десять вариантов - высоковероятно патогенные, один - неясного значения. Наиболее частой мутацией в выборке был аллель c.894G>A, что характерно для большинства европейских популяций. Частота данного аллеля у 920 новорожденных Москвы составила 1:270. Исходя из этого, расчетная частота встречаемости ДЛКЛ составила 1:73 159, что превышает ориентировочную оценку для РФ. Заключение. Целесообразен скрининг на ДЛКЛ пациентов с подозрением на ЛБН. Аллельная частот варианта c.894G>A среди выявленных вариантов гена LIPA сопоставима с таковой в европейских исследованиях. В отличие от этих работ у российских больных встретилось относительно много различных вариантов гена, ранее описываемых крайне редко или неописанных. Расчетная частота заболеваемости ДЛКЛ в г. Москве превышает предполагаемую для РФ. Background. Lysosomal acid lipase deficiency (LALD) is a continuum of autosomal recessive diseases caused by defects in the enzyme of lipid metabolism, lysosomal acid lipase (LAL). LAL encodes by the gene LIPA. The most common variant of LIPA c.894G>A caused the disease in more than а half of cases. The true frequency of LALD is unknown. In Russia it is supposed to be 1:150000 - 1:100000 of newborns. The aim of the work is the selective biochemical screening for LALD, the study of LIPA mutation spectrum and the estimation of the LALD incidence in Moscow. Materials and methods. 1999 рatients suspected of lysosomal storage diseases (LSD) took part in the study. Dried blood spots of 920 newborns of Moscow were obtained for the estimation of c.894G>A allelic frequency. LAL activity was measured by fluorometric analysis. The LIPA gene was studied by direct sequencing and RFLP-analysis. Results and discussion. In 34 cases diagnosis of LALD was confirmed. Totally, 16 different variants of LIPA were found, 11 variants were novel. Ten of the novel variants were classified as pathogenic, one was uncertain significance. The allele c.894G>A was the most common LIPA variant in the cohort of patients, so as in many Europe populations. The allelic frequency of the variant in the newborns collection was estimated as 1:270 and LALD frequence was 1:73.159. Conclusion. Screening for LALD is a useful tool for diagnostics among LSD suspected patients. The allelic frequency of the variant c.894G>A seems the same as in European populations. In comparison with this data, there are many rare and novel variants in the Russian cohort.

Mucopolysaccharidosis type I (MPS I) is the hereditary disease characterized with alpha-L-iduronidase activity decrease and further accumulation of heparan and dermatan sulfate in lysosomes. MPS I is rare autosomal recessive disorder with incidence of 0.5–4 cases on 100.000 live-birth infants. Meantime there two approaches in MPS I treatment: hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT). HSCT can be the best option for treatment of patients with severe MPS I (Hurler syndrome). Successful engraftment moderates such clinical signs as obstructive airway diseases, hepatosplenomegaly, cardiovascular system dysfunctions. HSCT prevents cognitive functions decline and other pathologic features of central nervous system. Presented clinical cases show various clinical courses according to age of diagnosis, ERT onset and HSCT implementation.

Generalized osteopetrosis is a rare hereditary disease characterized by impairment of skeleton bones formation, bone marrow dysfunction, neurologic deficiency and blindness. The main treatment for osteopetrosis is an allogeneic hematopoietic stem cell transplantation (allo-HSCT). To review and analyze experience of Department of bone marrow transplantation of RDKB (BMT RDKB) of allo-HSCT for patients with autosomal recessive generalized osteopetrosis; to evaluate tolerability and efficacy of the conditioning regiment administered. Between 2010 to 2018 years, 7 patients (2-male, 5-female) with autosomal recessive generalized osteopetrosis underwent allo-HSCT in tDepartment of bone marrow transplantation of RDKB. Median age at the moment of HSCT was 5,5 years (1–11 years). Before the transplantation myeloablative conditioning regimen was used: treosulfan, fludarabine and melphalan for 5 patients, treosulfan, fludarabine and thiotepa for 1 patient and treosulfan with fludarabine for 1 patient. In case of unrelated allo-HSCT antithymocyte globulin was added to the conditioning regimen. Bone marrow from matched (HLA- 10/10) unrelated donor was used for 4 patients, peripheral blood stem cells from matched unrelated donor was used for 1 patient, two grafts of unrelated umbilical cord blood (HLA 8/10 and 9/10) for 1 patient and peripheral blood stem cells from matched (HLA 10/10) from related donor – for 1 patient. For “graft-versus-host” disease (GVHD) prophylaxis either cyclosporine A/tacrolimus and methotrexate/ mofetil mycophenolate was used. White blood cell recovery had been achieved for 6 from 7 patients on +13 to +22 day (median +17 day). Quick autoreconstitution of hemopoesis was observed for the recipient of umbilical cord blood who got one myeloablative drug. The following early post transplantation complications were registered: oropharyngeal mucositis up to II degree in 6 patients, neutropenic enterocolitis up to II degree in 4 patients, up to III degree in 3 patients, sepsis in 3 patients. The GVHD symptoms occurred in 2 cases: skin form of II degree in one patient and skin form of II degree and intestinal form of IV degree in another patient. One patient with neurodegenerative form of osteopetrosis died with increase of hypertensive-hydrocephalus syndrome, cerebral edema with downward cerebellar herniation. During 5-6 months after allo-HSCT the 5 successfully transplanted patients experienced poor graft function but then reduction of extramedullary hemopoesis occurred and full engraftment was achieved. Hypercalcemia was reported in 2–5 months after allo-HSCT and was treated by administration of bisphosphonates. Visual impairment persisted after allo-HSCT. After 4–6 months after transplantation axis skeleton growth occurred for all 5 successfully transplanted patients, skull deformation reduced and no new zones of nerve’s compression were observed. No patients had any developmental delays after the treatment. Allo-HSCT is an effective systemic treatment of autosomal recessive generalized osteopetrosis. However because serious neurodegenerative condition cannot be reversed by allo-HSCT, such treatment may not be recommended for patients with heavy CNS impairment. Myeloablative conditioning regimen with two alkylating agents provides allogeneic reconstitution of hemopoesis. In post transplantation period, measures for hypercalcemia control are necessary. Early diagnostic of autosomal recessive generalized osteopetrosis can help to evaluate feasibility of allo-HSCT and to start treatment on time thus provide chance for long-term rehabilitation and prevention of serious disability. The study was approved by the Independent Ethics Committee of Russian Children's Clinical Hospital.

Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is an X-linked hereditary disorder associated with a deficiency of iduronate2-sulfatase (IDS). IDS deficiency provokes the accumulation of dermatan sulfate and heparan sulfate in different tissues. Clinical manifestations of MPS II are heterogeneous and involve different organs. Two phenotypes are distinguished: attenuated or severe; classification is based on central nervous system impairment signs. The review provides data on the current treatments opportunities for Hunter syndrome and perspectives for development of new therapeutic approaches. Current treatment includes intravenous enzyme replacement therapy (ERT), hematopoietic stem cell transplantation, and symptomatic treatment. Intravenous enzyme replacement therapy does not promote the enzyme to penetrate the blood-brain barrier which leads to the treatment failure for neurological signs and symptoms; hematopoietic stem cell transplantation has high risk of post-transplantation complications but can improve some neurological problems. Intrathecal ERT, substrate reduction, pharmacological chaperones, and gene therapy are currently under investigation as therapies for severe form of MPS II. Development of new approaches to treatment of Hunter syndrome and other hereditary diseases is extremely vital.

Generalized osteopetrosis is a rare hereditary disease characterized by systemic sclerosis of the bones of the skeleton, disorder of bone marrow hematopoiesis and, as a consequence, development of severe anemia and appearance of extramedullary hematopoiesis foci in various parenchymal organs. The problem of osteopetrosis is also relevant for the Russian Federation. A radical approach is the allogeneic hematopoietic stem cells transplantation (allo-HSCT). The article presents the experience of treating patients with osteopetrosis in the department of bone marrow transplantation of the Russian Children Clinical Hospital (RCCH). In the period from 2010 to 2017 allo-HSCT was performed in 6 patients with autosomal recessive form of osteopetrosis. The median age was 5.5 years (1–11 years). Allo-HSCT was performed using the myeloablative regimen of conditioning with treosulfan, fludarabine and melphalan. Reconstitution of donor leukopoiesis was recorded in 5 of 6 patients. In 1 patient, a recipient of umbilical cord blood, there was no reconstitution of donor leukopoiesis. In the early posttransplant period, severe toxic complications were not recorded. One patient had a graft-versus-host reaction, a cutaneous form, I degree. In 5 patients, hypercalcemia was observed in 2–5 months after HSCT, relieved by the admission of bisphosphonates. One patient with a neurodegenerative form of the disease died in the early posttransplant period during deterioration of a hydrocephalic-hypertensive syndrome (donor hematopoiesis was confirmed). In 4 patients with successful allo-HSCT, the follow-up period was from 5 to 42 months (median – 26 months). All patients have complete hematologic recovery, partial correction of the skull deformity, acceleration of growth rates of the body length. Thus, allo-HSCT is an effective method of systemic disease control. The defeat of the central nervous system is not corrected by allo-HSCT, which requires earlier diagnosis and the initiation of radical therapy before the onset of severe disability.

Niemann-pick disease type C is a rare autosomal recessive neurodegenerative disorder, the real incidence of which has been underestimated because of not specific clinical symptoms. The clinical symptoms of NP-C are highly variable with different onset terms of manifestations from fetal and neonatal period to adulthood. In recent years there has been a growing use of biomarkers as a selective screening and panel genetic tests which contributed to the earlier detection of the disease in patients. The article contains the most important clinical manifestations and their combinations, as well as an update to the existing recommendations for clinical practice.

Tyrosinemia type I (TH1) is an inborn autosomal recessive disorder of tyrosine catabolism caused by defective strength of fumarylacetoacetate hydrolase and mutations in FAH gene. The frequency of TH1 is approximately one in 100,000 to 120,000 live births worldwide. Several regions of the world have a higher expected frequency of TH1 due to an increased frequency of certain pathogenic variants resulting from the founder effect. In Norway, Finland and province of Quebec (Canada) the birth incidence is estimated as 1:74,000, 1:60,000 and 1:16,000 for live births, respectively. The frequency of TH1in whole Russia and in its regions is not known. To study the frequency and spectrum of mutations of HT1 in the Russian Federation, a number of ethnic groups belonging to different linguistic and geographical regions were explored. The mutation c.1025 C>T (Pro342Leu) whish constist (33.3% of all the mutant HT1 alleles) and is specific to the Chechen ethnic group. Among 296 newborn DBS from Chechen Republic, heterozygous carriers were found at a frequency of 0.0236 (the frequency of the mutant allele is 0.0118), which causes the calculated incidence rate HT1 at 1:7152, one of the most frequent rates worldwide. No single case of mutation of the pool leading to this disease was found among 201 newborn DBS from Dagestan. A previously undocumented mutation c.1090 G>C (Glu364Gln) was found in three Yakut, Buryat and Nenets patients in homozygous state. Detection of the ethno-specific mutations associated with HT1 in different populations of the Russian Federation is probably due to the founder effect.

The deficiency of lysosomic acid lipase is a rare hereditary enzymopathy. The focus of this article is the present condition of this issue. The authors demonstrate epidemiological data and etiopathogenetic features of two phenotypic forms of lysosomic acid lipase deficiency — Wolman disease and cholesterol ester storage disease. Clinical features of both — the rapidly progressing form and the slowly developing cholesterol ester storage disease — are described in detail in this article. The algorithm and crucial steps of differential diagnosis are described in detail. Also, indications to pathogenetic therapy are carefully formulated, and the tactic of enzyme replacing therapy is given. The modern approaches to the management of child patients are described.

Distonia is a movement disorder associated with imbalance of excitatory neurotransmitters, and it is characterized by continuous or episodic muscle contraction that forms repetitive stereotyped movements and/or postures. Dystonic hyperkinesia of younger children can be included into the structure of many syndromes that have different etiological factors, prognosis, and treatment. Different clinical variant of dystonia are represented: idiopathic benign dystonia with the onset in the first year of life; dystonia against the background of residual damage to the nervous system; hereditary idiopathic and symptomatic dystonia with various syndromes and metabolic diseases; similar conditions. Diagnostics of dystonia of children requires application of a wide range of examinations, including neuroimaging, continuous video electroencephalographic monitoring, genetic research. Differential diagnosis of dystonia of children is performed regarding various paroxysmal states of childhood of the epileptic and non-epileptic nature.

Background. Allogenic hematopoietic stem cell transplantation (allo-HSCT) for patients with mucopolysaccharidosis is the radical method of therapy nowadays. Myeloablative conditioning regimens allow to achieve good engraftment and do not compromise clinical status of a patient. Aim – to show effectiveness of allo-HSCT with myeloablative conditioning for patients with Hurler syndrome (HS). Patients and methods . We analyzed 23 allo-HSCT at 22 patients with HS which were performed in 2002–2015. HSCT from unrelated donors (10/10 and 9/10) were performed in 18 cases. Transplant: bone marrow – 73.9 % (n = 17); peripheral blood stem cells – 17.4 % (n = 4); cord blood (CB) – 8.7 % (n = 2). Age median – 1.86 y.o. (10 months – 3.8 years). Conditioning regimen: Busulphan/Treosulphan + Fludarabine + Thiotepa/Melphalan and Antithymocyte Immunoglobulin +/– Rituximab (in case of HSCT from unrelated donor). Results. 19 patients are alive now. 15 patients have complete donor’s chimerism now. All patients have good answer on general disease (best answer correlated with minimal interval between diagnosis and HSCT). Primary graft failure was in one case of CB transplantation. Graft rejection was diagnosed in 3 cases. Causes of death were infection complications in all cases. Results improved during last 5 years – good infection control and therapy of infection and immune complications. Median of follow-up is 48.62 (8–130) months, overall survival 83.2 %, event-free survival – 71.5 %. Conclusion. Our results suggested that allo-HSCT with myeloablative conditioning (with Melphalan inclusion) for the patients with HS is effective way of therapy to stop neurodegeneration processes. Optimization of prevention and treatment of infection complications and graftversus-host disease allows to improve significantly results of HSCT.