Congenital mitochondrial fatty acid beta-oxidation disorders are a heterogeneous group of metabolic disorders characterized by impaired fatty acid metabolism in mitochondria. It results in central nervous system, skeletal muscle, cardiovascular system, and liver damage, as well as the development of nonketotic hypoglycemia. The age of disease manifestation and its severity range from severe (neonatal) to milder myopathic (adult) forms. The extension of the mass screening program in Russian Federation allows to detect these diseases during the first weeks of life. The availability of effective therapy for mitochondrial fatty acid beta-oxidation disorders, especially during early diagnosis, enables timely stabilization of the patient's condition and prevention of severe complications. Awareness of pediatricians, neonatologists, neurologists, and cardiologists about such diseases is the urgent task of modern pediatrics.

Mucopolysaccharidosis (MPS) type IVA (Morquio syndrome) is a hereditary lysosomal storage disease caused by deficiency of N-acetylglucosamine-6-sulfate sulfatase. This enzyme deficiency leads to specific glycosaminoglycans (keratan sulfate and chondroitin-6sulfate) accumulation mainly in the bone and cartilage tissues, as well as in the cardiovascular, respiratory systems, and visual systems. Patients with MPS IVA look healthy at birth, however, they develop typical spine deformities (kyphoscoliosis), pectus carinatum, wrists hypermobility with decreased muscle strength and loss of fine motor skills, valgus deformation of lower limbs during the first years of life. Pathological changes in cardiovascular and respiratory systems, visual and acoustic analyzers can be revealed. Early diagnosis of the disease is crucial for timely initiation of enzyme replacement therapy. Thus, low incidence of the disease and its heterogeneous clinical picture complicates diagnosis. Consequently, patients with MAS IVA often become severely disabled as early as adolescence. Patients with severe form and without treatment die before the age of 30 due to complications of respiratory system diseases, valvular heart apparatus involvement, and cervical myelopathy.

Background. Onasemnogene abeparvovec is the first gene replacement therapy medication based on the adeno-associated viral vector (AAV9). One injection to a patient with 5q spinal muscular atrophy (SMA) leads to replacement of the missing or defective SMN1 gene with its functional copy. It leads to normalization of survival motor neuron protein (SMN) production.

Objective. The aim of the study is to evaluate efficacy, safety, and causes of different responses to therapy after single administration of onasemnogene abeparvovec in 5 patients with 5q SMA (types I and II) comparing the baseline status with the results of continued monitoring in real clinical practice in Russian Federation.

Methods. Interim results of continued follow-up of children with 5q SMA with 2–3 copies of the SMN2 gene are presented: 2 boys and 1 girl with type I who received single dose of onasemnogene abeparvovec at 4 and 7 months of age; and 2 girls with type II who received therapy at 11 and 16 months of age.

Results. Short-term controlled fever was observed in 4 out of 5 patients during first 2 weeks after viral vector therapy administration (max in patient 5 — up to 38.5 ° C). All 5 children had transaminases increase,  1 patient — significant transaminases increase during the sensitisation period (> 10 from upper normal level (UNL)), 1 patient — delayed significant transaminases increase (> 20 UNL), 1 patient — transaminases increase (> 3 UNL) after discontinuation of longterm therapy with glucocorticosteroids (according to prescribing information). All patients had shown positive and sustained response to therapy over time at motor status assessment via CHOP INTEND / HFMSE scales. The more significant response was observed in patients with less aggressive baseline 5q SMA type II with 3 copies of the SMN2 gene.

Conclusion. Onasemnogene abeparvovec is relatively safe medication for management of children with 5q SMA. Thus, the development of adverse events and their mechanisms should be further studied, as well as long-term follow-up of recipients is required to gather knowledge on this medication effects on human body.

Background. Differential diagnosis of attenuated forms of mucopolysaccharidosis (MPS) and juvenile idiopathic arthritis (JIA) can be challenging due to their similarities.

Objective. The aim of the study is to create simple diagnostic criteria (DScore) that would allow to differentiate MPS from JIA for earlier MPS diagnosis.

Methods. The retrospective multicenter study included analysis of clinical (joint, heart, eye involvement, hearing loss, hernias, psychomotor delay, noisy breathing, posture disorders, macrocephaly, hepatomegaly, splenomegaly, and growth delay) and laboratory data (ESR, CRP, hemoglobin, WBC, and platelets) from MPS patients (n = 41) and from rheumatoid factor-negative polyarticular category of JIA patients (n = 255). These variables allowed to differentiate both conditions and were used to create DScore.

Results. Patients with MPS had younger onset age, male predominance, height and weight delay, lower inflammation markers (WBC, platelets, and ESR), and usually involved joints, especially cervical spine, upper limbs joints, hip, and small foot joints. The prevalence of eye involvement was similar for both diseases, however, the type of involvement was different. JIA patients had uveitis and its’ complications and MPS patients — corneal opacity and cataract. No differences in CRP levels were revealed in most cases. The major diagnostic criterion of MPS was the presence of more than one extra-articular manifestation associated with polyarticular involvement. DScore has included 5 following criteria: ESR ≤ 11 mm/h (38 points), height ≤ -2.0 SD (20 points), onset age of articular manifestations ≤ 1.1 year (24 points), male gender (15 points), and symmetrical limitation of movements in elbow joints (29 points). The sum > 38 points allowed us to differentiate MPS and JIA with sensitivity of 92.7% and specificity of 91.0%.

Conclusion. This DScore can be used for differential diagnosis of mild MPS and JIA alongside with routine diagnostic procedures. DScore allows us to identify a group of patients with joint involvement who require MPS exclusion.

Background. Fibrodysplasia ossificans progressiva (FOP) is a genetic disease of the heterotopic ossification group associated with the mutation in ACVR1/ALK2 gene. FOP is characterized by progressive heterotopic endochondral ossification of connective tissue that occurs in postnatal period. It leads to formation of qualitatively normal bone in extraskeletal areas. Congenital hallux deformity   is typical for this disease. The clinical picture is characterized by aggravations that are usually caused by trauma or viral infections. Formation of Heterotopic ossificate formation can be observed during aggravations. There is no etiological treatment for FOP. Systemic glucocorticosteroids, non-steroidal anti-inflammatory drug (NSAIDs), mast cell stabilisers, antileukotriene drugs and bisphosphonates can be used in these patients.

Clinical case description. The child was born with congenital hallux deformity typical for FOP. The disease onset was noted at the age of 2 years 8 months with a tumor-like painful mass on the neck. Oncological (lymphoproliferative) disease was suspected but biopsy from the lesion did not confirm its malignant nature. The child was consulted by pediatric rheumatologist who has diagnosed FOP. Etanercept and zoledronic acid were administrated, though etanercept was later discontinued. For now, the child receives zoledronic acid infusions 2 times per year and daily NSAIDs.

Conclusion. The difficulties in FOP diagnosing are associated to its sporadic nature and clinical picture similarity to other diseases. Suspected malignancy leads to biopsy that is highly undesirable in FOP patients due to high risk of iatrogenic complications.

Background. Mucopolysaccharidosis type II (MPS II) is a rare hereditary disease from the group of lysosomal storage diseases, with progressive course. There is effective enzyme replacement therapy (ERT) for this disease, it prevents the development of severe complications and improves patients’ quality of life. Long-term follow-up of health changes in individuals on ERT is required for evaluating the treatment impact on disease progression and eventually on the quality of life of the patient and his family.

Clinical case description. Results of 14-year-long follow-up of the patient with MPS II who was the first patient on ERT with idursulfase in Russia are presented. Improvement of growth, decrease in ENT-organs infections frequency, liver and spleen sizes decrease, general stabilization, no progression in cardiovascular and respiratory events, normal levels of glycosaminoglycans in urine are shown.

Conclusion. Long-term therapy with idursulfase in severe MPS II stabilizes the patient’s somatic condition, prevents the development of severe complications in cardiovascular and respiratory systems, improves the quality of life of the patient and his family. Urinary glycosaminoglycans level decrease is the important indicator of the therapy efficacy along with overall patient's somatic state.

Background. Alfa-mannosidosis is ultra-rare autosomal recessive lysosomal storage disease caused by the mutation in the MAN2B1 gene. Pathogenic nucleotide variants and structural changes in this gene lead to acid alpha-mannosidase deficiency, this enzyme is involved in oligosaccharides degradation. This disease is characterized by multisystem involvement and chronic progressive course.

Clinical case description. The clinical case attracted our attention due to the late disease diagnosis in a boy living in a metropolis. The child has classic clinical manifestations of the disease: typical phenotype, spinal deformity, developmental speech and motor delays, hearing loss, hepatomegaly, splenomegaly, umbilical and inguinal hernias. Despite developmental speech delay and frequent recurrent otitis, the patient has not been referred to surdologist examination until the age of 4.5 years. Intriguing fact is the presence of congenital cataract that was the reason for surgery twice.

Conclusion. Congenital cataract is one of the early manifestation of this disease. 3 out of 8 patients with alfa-mannosidosis observed in our centre had congenital cataract. We assume that such patients should be referred to genetics for the early exclusion of alpha-mannosidosis. Late diagnosis and progressive course of the disease led to early disability of the patient. Nowadays, as enzyme replacement therapy is available, it is crucial to identify these patients timely in order to improve their quality of life and increase survivability.