18 results on '"Zakharova, Ekaterina Y."'
Search Results
2. Identification of a Novel Indel Variant in the DARS2 Gene in Russian Patients with Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation.
- Author
-
Bostanova, Fatima M., Tsygankova, Polina G., Larshina, Elena A., Nagornov, Ilya O., Evseeva, Yulia V., Krutikhina, Irina L., Dzhentemirova, Marina E., Kashlakova, Marina N., Petukhova, Marina S., Sharkova, Inna V., and Zakharova, Ekaterina Y.
- Subjects
SPINAL cord ,GENETIC variation ,FAMILIAL spastic paraplegia ,LEUKOENCEPHALOPATHIES ,WHOLE genome sequencing ,BRAIN stem - Abstract
Background: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation is an inherited disease caused by pathogenic biallelic variants in the gene DARS2, which encodes mitochondrial aspartyl-tRNA synthetase. This disease is characterized by slowly progressive spastic gait, cerebellar symptoms, and leukoencephalopathy with brainstem and spinal cord involvement. Case Presentation: Peripheral blood samples were collected from four patients from four unrelated families to extract genomic DNA. All patients underwent partial exon analysis of the DARS2 gene using Sanger sequencing, which detected the c.228-21_228-20delinsC variant in a heterozygous state. Further DNA from three patients was analyzed using a next-generation sequencing-based custom AmpliSeq™ panel for 59 genes associated with leukodystrophies, and one of the patients underwent whole genome sequencing. We identified a novel pathogenic variant c.1675-1256_*115delinsGCAACATTTCGGCAACATTCCAACC in the DARS2 gene. Three patients (patients 1, 2, and 4) had slowly progressive cerebellar ataxia, and two patients (patients 1 and 2) had spasticity. In addition, two patients (patients 2 and 4) showed signs of axonal neuropathy, such as decreased tendon reflexes and loss of distal sensitivity. Three patients (patients 1, 2, and 3) also had learning difficulties. It should be noted the persistent presence of characteristic changes in brain MRI in all patients, which emphasizes its importance as the main diagnostic tool for suspicion and subsequent confirmation of LBSL. Conclusions: We found a novel indel variant in the DARS2 gene in four patients with LBSL and described their clinical and genetic characteristics. These results expand the mutational spectrum of LBSL and aim to improve the laboratory diagnosis of this form of leukodystrophy. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
3. Molecular and biochemical study of glutaric aciduria type 1 in 49 Russian families: nine novel mutations in the GCDH gene
- Author
-
Kurkina, Marina V., Mihaylova, Svetlana V., Baydakova, Galina V., Saifullina, Elena V., Korostelev, Sergey A., Pyankov, Denis V., Kanivets, Ilya V., Yunin, Maksim A., Pechatnikova, Natalya L., and Zakharova, Ekaterina Y.
- Published
- 2020
- Full Text
- View/download PDF
4. Pediatric Patients with Sitosterolemia: Next-Generation Sequencing and Biochemical Examination in Clinical Practice.
- Author
-
Miroshnikova, Valentina V., Vasiluev, Petr A., Linkova, Svetlana V., Soloviov, Vladislav M., Ivanova, Olga N., Tolmacheva, Ekaterina R., Udalova, Vasilisa Y., Baranova, Polina V., Aleksandrova, Darya Y., Strokova, Tatiana V., Miklashevich, Irina M., Izumchenko, Artem D., Dracheva, Kseniia V., Grunina, Maria N., Smirnova, Nataliya N., Kuchina, Anna S., Zakharova, Ekaterina Y., and Pchelina, Sofya N.
- Subjects
CHILD patients ,NUCLEOTIDE sequencing ,GENETIC variation ,GENETIC disorders ,STEROLS - Abstract
Here, we report the pediatric cases of sitosterolemia, a rare autosomal-recessive genetic disorder, characterized by high concentrations of plant sterols in blood and heterogeneity manifestations. All three patients (two girls aged 2 and 6 years old, and one boy aged 14 years old) were initially diagnosed with hypercholesterinemia. Next-generation sequencing (NGS) revealed homozygous (p.Leu572Pro/p.Leu572Pro) and compound (p.Leu572Pro/p.Gly512Arg and p.Leu572Pro/p.Trp361*) variants in the ABCG8 gene that allowed for the diagnosis of sitosterolemia. Two patients whose blood phytosterol levels were estimated before the diet demonstrated high levels of sitosterol/campesterol (69.6/29.2 and 28.3/12.4 μmol/L, respectively). Here, we demonstrate that NGS-testing led to the proper diagnosis that is essential for patients' management. The variant p.Leu572Pro might be prevalent among patients with sitosterolemia in Russia. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
5. Oxysterol/chitotriosidase based selective screening for Niemann-Pick type C in infantile cholestasis syndrome patients
- Author
-
Degtyareva, Anna V., Proshlyakova, Tatiana Y., Gautier, Marina S., Degtyarev, Dmitry N., Kamenets, Elena A., Baydakova, Galina V., Rebrikov, Denis V., and Zakharova, Ekaterina Y.
- Published
- 2019
- Full Text
- View/download PDF
6. Chronic visceral acid sphingomyelinase deficiency (Niemann-Pick disease type B) in 16 Polish patients: long-term follow-up
- Author
-
Lipiński, Patryk, Kuchar, Ladislav, Zakharova, Ekaterina Y., Baydakova, Galina V., Ługowska, Agnieszka, and Tylki-Szymańska, Anna
- Published
- 2019
- Full Text
- View/download PDF
7. New Acylcarnitine Ratio as a Reliable Indicator of Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency.
- Author
-
Baydakova, Galina V., Tsygankova, Polina G., Pechatnikova, Natalia L., Bazhanova, Olga A., Nazarenko, Yana D., and Zakharova, Ekaterina Y.
- Published
- 2023
- Full Text
- View/download PDF
8. Potential Binding Sites of Pharmacological Chaperone NCGC00241607 on Mutant β-Glucocerebrosidase and Its Efficacy on Patient-Derived Cell Cultures in Gaucher and Parkinson's Disease.
- Author
-
Kopytova, Alena E., Rychkov, George N., Cheblokov, Alexander A., Grigor'eva, Elena V., Nikolaev, Mikhail A., Yarkova, Elena S., Sorogina, Diana A., Ibatullin, Farid M., Baydakova, Galina V., Izyumchenko, Artem D., Bogdanova, Daria A., Boitsov, Vitali M., Rybakov, Akim V., Miliukhina, Irina V., Bezrukikh, Vadim A., Salogub, Galina N., Zakharova, Ekaterina Y., Pchelina, Sofya N., and Emelyanov, Anton K.
- Subjects
MOLECULAR chaperones ,GAUCHER'S disease ,PARKINSON'S disease ,BINDING sites ,CELL culture ,INDUCED pluripotent stem cells - Abstract
Mutations in the GBA1 gene, encoding the lysosomal enzyme glucocerebrosidase (GCase), cause Gaucher disease (GD) and are the most common genetic risk factor for Parkinson's disease (PD). Pharmacological chaperones (PCs) are being developed as an alternative treatment approach for GD and PD. To date, NCGC00241607 (NCGC607) is one of the most promising PCs. Using molecular docking and molecular dynamics simulation we identified and characterized six allosteric binding sites on the GCase surface suitable for PCs. Two sites were energetically more preferable for NCGC607 and located nearby to the active site of the enzyme. We evaluated the effects of NCGC607 treatment on GCase activity and protein levels, glycolipids concentration in cultured macrophages from GD (n = 9) and GBA-PD (n = 5) patients as well as in induced human pluripotent stem cells (iPSC)—derived dopaminergic (DA) neurons from GBA-PD patient. The results showed that NCGC607 treatment increased GCase activity (by 1.3-fold) and protein levels (by 1.5-fold), decreased glycolipids concentration (by 4.0-fold) in cultured macrophages derived from GD patients and also enhanced GCase activity (by 1.5-fold) in cultured macrophages derived from GBA-PD patients with N370S mutation (p < 0.05). In iPSC-derived DA neurons from GBA-PD patients with N370S mutation NCGC607 treatment increased GCase activity and protein levels by 1.1-fold and 1.7-fold (p < 0.05). Thus, our results showed that NCGC607 could bind to allosteric sites on the GCase surface and confirmed its efficacy on cultured macrophages from GD and GBA-PD patients as well as on iPSC-derived DA neurons from GBA-PD patients. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
9. Biochemical Characteristics of iPSC-Derived Dopaminergic Neurons from N370S GBA Variant Carriers with and without Parkinson's Disease.
- Author
-
Grigor'eva, Elena V., Kopytova, Alena E., Yarkova, Elena S., Pavlova, Sophia V., Sorogina, Diana A., Malakhova, Anastasia A., Malankhanova, Tuyana B., Baydakova, Galina V., Zakharova, Ekaterina Y., Medvedev, Sergey P., Pchelina, Sofia N., and Zakian, Suren M.
- Subjects
DOPAMINERGIC neurons ,LOCUS coeruleus ,PARKINSON'S disease ,LIQUID chromatography-mass spectrometry ,INDUCED pluripotent stem cells ,DOPAMINE receptors - Abstract
GBA variants increase the risk of Parkinson's disease (PD) by 10 times. The GBA gene encodes the lysosomal enzyme glucocerebrosidase (GCase). The p.N370S substitution causes a violation of the enzyme conformation, which affects its stability in the cell. We studied the biochemical characteristics of dopaminergic (DA) neurons generated from induced pluripotent stem cells (iPSCs) from a PD patient with the GBA p.N370S mutation (GBA-PD), an asymptomatic GBA p.N370S carrier (GBA-carrier), and two healthy donors (control). Using liquid chromatography with tandem mass spectrometry (LC-MS/MS), we measured the activity of six lysosomal enzymes (GCase, galactocerebrosidase (GALC), alpha-glucosidase (GAA), alpha-galactosidase (GLA), sphingomyelinase (ASM), and alpha-iduronidase (IDUA)) in iPSC-derived DA neurons from the GBA-PD and GBA-carrier. DA neurons from the GBA mutation carrier demonstrated decreased GCase activity compared to the control. The decrease was not associated with any changes in GBA expression levels in DA neurons. GCase activity was more markedly decreased in the DA neurons of GBA-PD patient compared to the GBA-carrier. The amount of GCase protein was decreased only in GBA-PD neurons. Additionally, alterations in the activity of the other lysosomal enzymes (GLA and IDUA) were found in GBA-PD neurons compared to GBA-carrier and control neurons. Further study of the molecular differences between the GBA-PD and the GBA-carrier is essential to investigate whether genetic factors or external conditions are the causes of the penetrance of the p.N370S GBA variant. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
10. Clinical and Genetic Characteristics of Pediatric Patients with Hypophosphatasia in the Russian Population.
- Author
-
Glotov, Oleg S., Savostyanov, Kirill V., Nagornova, Tatyana S., Chernov, Alexandr N., Fedyakov, Mikhail A., Raspopova, Aleksandra N., Krasnoukhov, Konstantin N., Danilov, Lavrentii G., Moiseeva, Nadegda V., Kalinin, Roman S., Tsai, Victoria V., Eismont, Yuri A., Voinova, Victoria Y., Vitebskaya, Alisa V., Gurkina, Elena Y., Kuzenkova, Ludmila M., Sosnina, Irina B., Pushkov, Alexander A., Zhanin, Ilya S., and Zakharova, Ekaterina Y.
- Subjects
CHILD patients ,RUSSIANS ,HYPOPHOSPHATASIA ,GENETIC variation ,ALKALINE phosphatase - Abstract
(1) Hypophosphatasia (HPP) is a rare inherited disease caused by mutations (pathogenic variants) in the ALPL gene which encodes tissue-nonspecific alkaline phosphatase (TNSALP). HPP is characterized by impaired bone mineral metabolism due to the low enzymatic activity of TNSALP. Knowledge about the structure of the gene and the features and functions of various ALPL gene variants, taking into account population specificity, gives an understanding of the hereditary nature of the disease, and contributes to the diagnosis, prevention, and treatment of the disease. The purpose of the study was to describe the spectrum and analyze the functional features of the ALPL gene variants, considering various HPP subtypes and clinical symptoms in Russian children. (2) From 2014–2021, the study included the blood samples obtained from 1612 patients with reduced alkaline phosphatase activity. The patients underwent an examination with an assessment of their clinical symptoms and biochemical levels of TNSALP. DNA was isolated from dried blood spots (DBSs) or blood from the patients to search for mutations in the exons of the ALPL gene using Sanger sequencing. The PCR products were sequenced using a reagent BigDye Terminator 3.1 kit (Applied Biosystems). Statistical analysis was performed using the GraphPad Prism 8.01 software. (3) The most common clinical symptoms in Russian patients with HPP and two of its variants (n = 22) were bone disorders (75%), hypomyotonia (50%), and respiratory failure (50%). The heterozygous carriage of the causal variants of the ALPL gene was detected in 225 patients. A total of 2 variants were found in 27 patients. In this group (n = 27), we identified 28 unique variants of the ALPL gene, of which 75.0% were missense, 17.9% were frameshift, 3.6% were splicing variants, and 3.6% were duplications. A total of 39.3% (11/28) of the variants were pathogenic, with two variants being probably pathogenic, and 15 variants had unknown clinical significance (VUS). Among the VUS group, 28.6% of the variants (7/28) were discovered by us for the first time. The most common variants were c.571G > A (p.Glu191Lys) and c.1171del (Arg391Valfs*12), with frequencies of 48.2% (13/28) and 11% (3/28), respectively. It was found that the frequency of nonsense variants of the ALPL gene was higher (p < 0.0001) in patients with the perinatal form compared to the infantile and childhood forms of HPP. Additionally, the number of homozygotes in patients with the perinatal form exceeded (p < 0.01) the frequencies of these genotypes in children with infantile and childhood forms of HPP. On the contrary, the frequencies of the compound-heterozygous and heterozygous genotypes were higher (p < 0.01) in patients with infantile childhood HPP than in perinatal HPP. In the perinatal form, residual TNSALP activity was lower (p < 0.0005) in comparison to the infantile and childhood (p < 0.05) forms of HPP. At the same time, patients with the heterozygous and compound-heterozygous genotypes (mainly missense variants) of the ALPL gene had greater residual activity (of the TNSALP protein) regarding those homozygous patients who were carriers of the nonsense variants (deletions and duplications) of the ALPL gene. Residual TNSALP activity was lower (p < 0.0001) in patients with pathogenic variants encoding the amino acids from the active site and the calcium and crown domains in comparison with the nonspecific region of the protein. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
11. Mucopolysaccharidosis-Plus Syndrome: Report on a Polish Patient with a Novel VPS33A Variant with Comparison with Other Described Patients.
- Author
-
Lipiński, Patryk, Szczałuba, Krzysztof, Buda, Piotr, Zakharova, Ekaterina Y., Baydakova, Galina, Ługowska, Agnieszka, Różdzyńska-Świątkowska, Agnieszka, Cyske, Zuzanna, Węgrzyn, Grzegorz, Pollak, Agnieszka, Płoski, Rafał, and Tylki-Szymańska, Anna
- Subjects
EXUDATES & transudates ,JOINT diseases ,GLYCOSAMINOGLYCANS ,LYSOSOMAL storage diseases - Abstract
Eleven patients from Yakutia with a new lysosomal disease assumed then as mucopolysaccharidosis-plus syndrome (MPS-PS) were reported by Gurinova et al. in 2014. Up to now, a total number of 39 patients have been reported; in all of them, the c.1492C>T (p.Arg498Trp) variant of the VPS33A gene was detected. Here, we describe the first Polish MPS-PS patient with a novel homozygous c.599G>C (p.Arg200Pro) VPS33A variant presenting over 12 years of follow-up with some novel clinical features, including fetal ascites (resolved spontaneously), recurrent joint effusion and peripheral edemas, normal growth, and visceral obesity. Functional analyses revealed a slight presence of chondroitin sulphate (only) in urine glycosaminoglycan electrophoresis, presence of sialooligosaccharides in urine by thin-layer chromatography, and normal results of lysosomal enzymes activity and lysosphingolipids concentration in dried blood spot. The comparison with other MPS-PS described cases was also provided. The presented description of the natural history of MPS-PS in our patient may broaden the spectrum of phenotypes in this disease. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
12. Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation: High Outcome Variation between Two Siblings
- Author
-
Tylki-Szymanska, Anna, Jurkiewicz, Elzbieta, Zakharova, Ekaterina Y., and Bobek-Billewicz, Barbara
- Published
- 2014
- Full Text
- View/download PDF
13. A Clinical Case of a Homozygous Deletion in the APOA5 Gene with Severe Hypertriglyceridemia.
- Author
-
Vasiluev, Petr Andreevich, Ivanova, Olga N., Semenova, Natalia A., Strokova, Tatiana V., Taran, Natalia N., Chubykina, Uliana V., Ezhov, Marat V., Zakharova, Ekaterina Y., Dadli, Elena L., and Kutsev, Sergey I.
- Subjects
LIPID metabolism disorders ,HYPERTRIGLYCERIDEMIA ,DELETION mutation ,GENETIC variation ,SYMPTOMS - Abstract
Background: Hypertriglyceridemia (HTG) is one of the most common forms of lipid metabolism disorders. The leading clinical manifestations are pancreatitis, atherosclerotic vascular lesions, and the formation of eruptive xanthomas. The most severe type of HTG is primary (or hereditary) hypertriglyceridemia, linked to pathogenic genetic variants in LPL, APOC2, LMF1, and APOA5 genes. Case: We present a clinical case of severe primary hypertriglyceridemia (TG level > 55 mmol/L in a 4-year-old boy) in a consanguineous family. The disease developed due to a previously undescribed homozygous deletion in the APOA5 gene (NM_052968: c.579_592delATACGCCGAGAGCC p.Tyr194Gly*68). We also evaluate the clinical significance of a genetic variant in the LPL gene (NM_000237.2: c.106G>A (rs1801177) p.Asp36Asn), which was previously described as a polymorphism. In one family, we also present a different clinical significance even in heterozygous carriers: from hypertriglyceridemia to normotriglyceridemia. We provide evidence that this heterogeneity has developed due to polymorphism in the LPL gene, which plays the role of an additional trigger. Conclusions: The homozygous deletion of the APOA5 gene is responsible for the severe hypertriglyceridemia, and another SNP in the LPL gene worsens the course of the disease. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
14. BH4-deficient hyperphenylalaninemia in Russia.
- Author
-
Gundorova, Polina, Kuznetcova, Irina A., Baydakova, Galina V., Stepanova, Anna A., Itkis, Yulia S., Kakaulina, Victoria S., Alferova, Irina P., Lyazina, Lidya V., Andreeva, Lilya P., Kanivets, Ilya, Zakharova, Ekaterina Y., Kutsev, Sergey I., and Polyakov, Aleksander V.
- Subjects
NEWBORN screening ,GENES ,TETRAHYDROBIOPTERIN ,SPECTRUM analysis ,PHENYLKETONURIA ,MIDDLE East respiratory syndrome - Abstract
A timely detection of patients with tetrahydrobiopterin (BH
4 ) -deficient types of hyperphenylalaninemia (HPABH4 ) is important for assignment of correct therapy, allowing to avoid complications. Often HPABH4 patients receive the same therapy as phenylalanine hydroxylase (PAH) -deficiency (phenylketonuria) patients—dietary treatment—and do not receive substitutive BH4 therapy until the diagnosis is confirmed by molecular genetic means. In this study, we present a cohort of 30 Russian patients with HPABH4 with detected variants in genes causing different types of HPA. Family diagnostics and biochemical urinary pterin spectrum analyses were carried out. HPABH4 A is shown to be the prevalent type, 83.3% of all HPABH4 cases. The mutation spectrum for the PTS gene was defined, the most common variants in Russia were p.Thr106Met—32%, p.Asn72Lys—20%, p.Arg9His—8%, p.Ser32Gly—6%. We also detected 7 novel PTS variants and 3 novel QDPR variants. HPABH4 prevalence was estimated to be 0.5–0.9% of all HPA cases in Russia, which is significantly lower than in European countries on average, China, and Saudi Arabia. The results of this research show the necessity of introducing differential diagnostics for HPABH4 into neonatal screening practice. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
15. Identification of novel variants in the LDLR gene in Russian patients with familial hypercholesterolemia using targeted sequencing.
- Author
-
MIROSHNIKOVA, VALENTINA V., ROMANOVA, OLGA V., IVANOVA, OLGA N., FEDYAKOV, MIKHAIL A., PANTELEEVA, ALEXANDRA A., BARBITOFF, YURY A., MUZALEVSKAYA, MARIA V., URAZGILDEEVA, SOREJYA A., GUREVICH, VICTOR S., URAZOV, STANISLAV P., SCHERBAK, SERGEY G., SARANA, ANDREY M., SEMENOVA, NATALIA A., ANISIMOVA, INGA V., GUSEVA, DARYA M., PCHELINA, SOFYA N., GLOTOV, ANDREY S., ZAKHAROVA, EKATERINA Y., and GLOTOV, OLEG S.
- Subjects
GENES ,HYPERCHOLESTEREMIA ,AGE groups ,PROTEIN domains ,RUSSIANS ,FAMILIAL hypercholesterolemia ,RECESSIVE genes - Abstract
Familial hypercholesterolemia (FH) is caused by mutations in various genes, including the LDLR, APOB and PSCK9 genes; however, the spectrum of these mutations in Russian individuals has not been fully investigated. In the present study, mutation screening was performed on the LDLR gene and other FH‑associated genes in patients with definite or possible FH, using next‑generation sequencing. In total, 59 unrelated patients were recruited and sorted into two separate groups depending on their age: Adult (n=31; median age, 49; age range, 23‑70) and children/adolescent (n=28; median age, 11; age range, 2‑21). FH‑associated variants were identified in 18 adults and 25 children, demonstrating mutation detec‑ tion rates of 58 and 89% for the adult and children/adolescent groups, respectively. In the adult group, 13 patients had FH‑associated mutations in the LDLR gene, including two novel variants [NM_000527.4: c.433_434dupG p.(Val145Glyfs*35) and c.1186G>C p.(Gly396Arg)], 3 patients had APOB mutations and two had ABCG5/G8 mutations. In the chil‑ dren/adolescent group, 21 patients had FH‑causing mutations in the LDLR gene, including five novel variants [NM_000527.4: c.325T>G p.(Cys109Gly), c.401G>C p.(Cys134Ser), c.616A>C p.(Ser206Arg), c.1684_1691delTGGCCCAA p.(Pro563Hisfs*14) and c.940+1_c.940+4delGTGA], and 2 patients had APOB mutations, as well as ABCG8 and LIPA mutations, being found in different patients. The present study reported seven novel LDLR variants considered to be patho‑ genic or likely pathogenic. Among them, four missense variants were located in the coding regions, which corresponded to functional protein domains, and two frameshifts were identified that produced truncated proteins. These variants were observed only once in different patients, whereas a splicing variant in intron 6 (c.940+1_c.940+4delGTGA) was detected in four unre‑ lated individuals. Previously reported variants in the LDLR, APOB, ABCG5/8 and LIPA genes were observed in 33 patients. The LDLR p.(Gly592Glu) variant was detected in 6 patients, representing 10% of the FH cases reported in the present study, thus it may be a major variant present in the Russian population. In conclusion, the present study identified seven novel variants of the LDLR gene and broadens the spectrum of mutations in FH‑related genes in the Russian Federation. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
16. Hepatic glycogen synthase (GYS2) deficiency: seven novel patients and seven novel variants.
- Author
-
Kamenets, Elena A., Gusarova, Elena A., Milovanova, Natalia V., Itkis, Yulia S., Strokova, Tatiana V., Melikyan, Maria A., Garyaeva, Irina V., Rybkina, Irina G., Nikitina, Natalia V., and Zakharova, Ekaterina Y.
- Published
- 2020
- Full Text
- View/download PDF
17. Plasma FGF‐21 and GDF‐15 are elevated in different inherited metabolic diseases and are not diagnostic for mitochondrial disorders.
- Author
-
Tsygankova, Polina G., Itkis, Yulia S., Krylova, Tatiana D., Kurkina, Marina V., Bychkov, Igor O., Ilyushkina, Aleksandra A., Zabnenkova, Viktoria V., Mikhaylova, Svetlana V., Pechatnikova, Natalia L., Sheremet, Natalia L., and Zakharova, Ekaterina Y.
- Abstract
Recently, the plasma cytokines FGF‐21 and GDF‐15 were described as cellular metabolic regulators. They share an endocrine function and are highly expressed in the liver under stress and during starvation. Several studies found that these markers have high sensitivity and specificity for the diagnosis of mitochondrial diseases, especially those with prominent muscular involvement. In our study, we aimed to determine whether these markers could help distinguish mitochondrial diseases from other groups of inherited diseases. We measured plasma FGF‐21 and GDF‐15 concentrations in 122 patients with genetically confirmed primary mitochondrial disease and 127 patients with non‐mitochondrial inherited diseases. Although GDF‐15 showed better analytical characteristics (sensitivity = 0.66, specificity = 0.64, area under the curve [AUC] = 0.88) compared to FGF‐21 (sensitivity = 0.51, specificity = 0.76, AUC = 0.78) in the pediatric group of mitochondrial diseases, both markers were also elevated in a variety of non‐mitochondrial diseases, especially those with liver involvement (Gaucher disease, galactosemia, glycogenosis types 1a, 1b, 9), organic acidurias and some leukodystrophies. Thus, the overall positive and negative predictive values were not acceptable for these measurements to be used as diagnostic tests for mitochondrial diseases (FGF‐21 positive predictive value [PPV] = 34%, negative predictive value [NPV] = 73%; GDF‐15 PPV = 47%, NPV = 28%). We suggest that FGF‐21 and GDF‐15 increase in patients with metabolic diseases with metabolic or oxidative stress and inflammation. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
18. Diagnostic Algorithm for Cholesteryl Ester Storage Disease: Clinical Presentation in 19 Polish Patients.
- Author
-
Lipiński, Patryk, Ługowska, Agnieszka, Zakharova, Ekaterina Y., Socha, Piotr, and Tylki-Szymańska, Anna
- Published
- 2018
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.