A Different SLC2A1 Gene Mutation in Glut 1 Deficiency Syndrome: c.734A>C

Background: Glucose transporter type 1 deficiency syndrome is the result of impaired glucose transport into the brain. Patients with glucose transporter type 1 syndrome may present with infantile seizures, developmental delay, acquired microcephaly, spasticity and ataxia. Case Report: Here, we report a rare case of glucose transporter type 1 deficiency syndrome caused by a different pathogenic variant in a 10-day-old neonate who presented with intractable seizures and respiratory arrest. Conclusion: This new pathogenic variant can be seen in glucose transporter type 1 deficiency syndrom

Mukopolisakaridozlar için muhtemel tanısal belirteçler; Katepsin-D, Galektin-3 ve Kitotriosidaz

Objective: Mucopolysaccharidoses is a group of inherited lysosomal storage diseases that are manifested by various clinical signs and symptoms (skeletal dysplasia, coarse face, progressive psychomotor retardation, cardiac and lung involvement) due to the deposition of glycosaminoglycans in tissues. Recently it has been shown that the inflammatory response to glycosaminoglycan deposition in leucocytes in animal models of mucopolysaccaridoses has increased. Here, we aimed to investigate some inflammatory markers (galectin-3, cathepsin-D and chitotriosidase) as diagnostic markers in different types of mucopolysaccharidosis and in patients with Gaucher disease and Niemann Pick A/B disease.Methods: Plasma samples were collected from patients with mucopolysaccharidosis (n=25), Gaucher Disease (n=16), Niemann Pick A/B (n=5) and 15 healthy controls. All subjects were under the age of 18 years. Chitotriosidase enzyme activities were determined fluorometrically, cathepsin-D and galectin-3 levels were determined by using the ELISA kit. Results: Chitotriosidase enzyme activities were statistically significantly higher in patients with MPS IV than the control group. Cathepsin-D levels were higher in patients with MPS I, MPS III and MPS IV, galectin-3 levels were higher in patients with MPS I, MPS IV and MPS VI when compared to healthy controls. All three parameters were higher in patients with Gaucher disease and Niemann Pick A/B disease. Conclusion: Elevated levels of galectin-3 in MPS I, MPS IV and MPS VI and elevated levels of cathepsin-D in MPS I, MPS III and MPS VI support the influence of inflammatory process in the pathophysiology of mucopolysaccharidosis and might be promising new biomarkers in the diagnosis with high sensitivity and specificity.Amaç: Mukopolisakkaridozlar dokulardaki glikozaminoglikanların birikimi nedeniyle çeşitli klinik belirti ve semptomlar (iskelet displazisi, seyir yüzü, ilerleyici psikomotor gerilik, kalp ve akciğer tutulumu) ile kendini gösteren kalıtsal lizozomal depolama hastalıkları grubudur. Son zamanlarda, mukopolisakaridoz hayvan modellerinde lökositlerdeki glikosaminoglikan birikimine verilen enflamatuvar yanıtın arttığı gösterilmiştir. Bu çalışmada, çeşitli mukopolisakaridoz tipleri ile Gaucher ve Niemann Pick A/B hastalıklarında bazı inflamatuvar proteinleri (galektin-3, katepsin-D ve kitotriozidaz) tanısal belirteç olarak araştırmayı ve bu proteinlerin düzeylerini karşılaştırmayı amaçladık. Yöntem: Mukopolisakaridozlu 25 mukopolisakkaridoz, 16 Gaucher, 5 Niemann Pick A/B hastası ve 15 sağlıklı kontrolten plazma örnekleri alındı. Tüm denekler 18 yaşın altındaydı. Tüm hastalarda kitotriyozidaz enzim aktiviteleri florometrik olarak belirlendi. Kandaki katepsin-D ve galektin-3 seviyeleri, ELISA kiti kullanılarak belirlendi. Bulgular: MPS IV hastalarında kitotriyozidaz enzim aktiviteleri, kontrol grubuna göre istatistiksel olarak daha yüksekti. MPS I, MPS III ve MPS IV hastalarında katepsin-D düzeyleri ve MPS I, MPS IV ve MPS VI hastalarında galektin-3 düzeyleri sağlıklı kontrollerle karşılaştırıldı- ğında daha yüksekti. Gaucher hastalığı ve Niemann Pick A/B hastalarında üç parametrenin hepsi kontrollere göre anlamlı olarak artış göstermişti. Sonuç: MPS I, MPS IV ve MPS VI hastalarında yüksek seviyelerde galektin-3 seviyeleri ve MPS I, MPS III ve MPS VI hastalarında artmış kathepsin-D seviyeleri, mukopolisakaridoz patofizyolojisinde inflamatuvar sürecin etkisini desteklemekte, yüksek duyarlılık ve özgünlük ile tanıda yeni bir biyolojik belirteç olarak kullanılmayı vadetmektedir

Clinical and Molecular Features of Our Pompe Patients: Single-Center Experience

Introduction: Pompe disease (PD), glycogen storage disease Type II (GSD II), is an autosomal recessive inherited lysosomal storage disease caused by pathogenicvariants in the GAA gene that encodes lysosomal acid ?-glucosidadase (GAA) enzyme. The incidence of the disease varies from country to country. PD is mainlypresents as two groups of phenotypes as infantile-onset Pompe disease (IOPD) and late-onset Pompe disease.Objective: The aim of this study is to discuss the molecular and clinical characteristics of infantile-onset Pompe disease (IOPD) and late-onset pompe disease(LOPD) followed-up in our center.Method: A total of 10 patients diagnosed with IOPD and 4 patients diagnosed with LOPD in Izmir Dr. Behcet Uz Pediatric Health and Diseases and Surgery Trainingand Research Hospital Pediatric Metabolism Unit between 06.01.2015 and 06.01. 2019 were included in the study. The patients’ demographic characteristics,clinical findings at the time of diagnosis and during the folllow-up period, biochemical findings, muscle biopsy data, results of enzymatic analyses and moleculargenetic characteristics were recorded retrospectively.Results: A total of 10 patients were included in the study. 7 patients were diagnosed with IOPD and 3 patients with LOPD. The median follow-up period of allpatients was 26 months (range: 6-42 months). The c.896 C> T (8/32, 25%) is detected as the most common variant. 1237G>T (p.Asp413Tyr), c.2019 C>A(p.Asn673Lys), c.418A>T (p.Asn140Tyr) variants were detected for the first time.Conclusion: Pompe disease is one of the most important congenital metabolic diseases in which early diagnosis and treatment are of great importance. Despitethe significant improvement in disease prognosis with the introduction of enzyme replacement therapy, there are still patients with poor prognosis despite earlydiagnosis. Phenotype-genotype studies are crucial in this respect

Pompe Tanısı Alan Hastalarımızın Klinik ve Moleküler Özellikleri: Tek Merkez Deneyimi

Introduction: Pompe disease (PD), glycogen storage disease Type II (GSD II), is an autosomal recessive inherited lysosomal storage disease caused by pathogenic variants in the GAA gene that encodes lysosomal acid ?-glucosidadase (GAA) enzyme. the incidence of the disease varies from country to country. PD is mainly presents as two groups of phenotypes as infantile-onset Pompe disease (IOPD) and late-onset Pompe disease. Objective: the aim of this study is to discuss the molecular and clinical characteristics of infantile-onset Pompe disease (IOPD) and late-onset pompe disease (LOPD) followed-up in our center. Method: A total of 10 patients diagnosed with IOPD and 4 patients diagnosed with LOPD in Izmir Dr. Behcet Uz Pediatric Health and Diseases and Surgery Training and Research Hospital Pediatric Metabolism Unit between 06.01.2015 and 06.01. 2019 were included in the study. the patients’ demographic characteristics, clinical findings at the time of diagnosis and during the folllow-up period, biochemical findings, muscle biopsy data, results of enzymatic analyses and moleculargenetic characteristics were recorded retrospectively. Results: A total of 10 patients were included in the study. 7 patients were diagnosed with IOPD and 3 patients with LOPD. the median follow-up period of all patients was 26 months (range: 6-42 months). the c.896 C> T (8/32, 25%) is detected as the most common variant. 1237G>T (p.Asp413Tyr), c.2019 C>A (p.Asn673Lys), c.418A>T (p.Asn140Tyr) variants were detected for the first time. Conclusion: Pompe disease is one of the most important congenital metabolic diseases in which early diagnosis and treatment are of great importance. Despite the significant improvement in disease prognosis with the introduction of enzyme replacement therapy, there are still patients with poor prognosis despite early diagnosis. Phenotype-genotype studies are crucial in this respect.Giriş: Pompe hastalığı (PD), glikojen depo hastalığı Tip II (GSD II), lizozomal acid?-glucosidadase (GAA) enzimini kodlayan GAA genindeki patojenik varyantlar sonucu ortaya çıkan otozomal resesif kalıtımlı lizozomal depo hastalığıdır. Hastalığın sıklığı ülkeden ülkeye değişmektedir. Temel olarak erken başlangıçlı pompe hastalığı (IOPD) ve geç başlangıçlı pompe hastalığı (LOPD) olmak üzere iki gruba ayrılır. Amaç: Çalışmamız, merkezimizde izlenen LOPD hem IOPD hastalarının moleküler ve klinik özelliklerinin tartışılmasını amaçlamaktadır. Yöntem: Çalışmamıza 01.06.2015-01.06.2019 tarihleri arasında İzmir Dr.Behçet Uz Çocuk Sağlığı ve Hastalıkları ve Cerrahisi Eğitim Araştırma Hastanesi Çocuk Metabolizma Ünitesi’nde IOPD hastalığı tanısı alan toplam 10 hasta ve LOPD tanısı alan 4 hasta dahil edilmiştir. Hastaların retrospektif olarak demografik özel- likleri, tanı anındaki ve izlem sırasındaki klinik bulguları, biyokimyasal bulguları, kas biyopsisi verileri, enzimatik analiz sonuçları ve moleküler-genetik özellikleri kayıt altına alındı. Bulgular: Çalışmamıza toplam 10 hasta dahil edilmiştir. 7 hasta IOPD, 3 hasta LOPD tanısı almıştır. Tüm hastaların izlem süresi median 26 ay (range: 6-42 ay) olarak saptanmıştır. En sık görülen varyant c.896 C>T (8/32, %25) olarak saptanmıştır. 1237G>T (p.Asp413Tyr), c.2019 C>A (p.Asn673Lys), c.418A>T (p.Asn140Tyr) varyantları ilk kez saptanmıştır. Sonuç: Pompe hastalığı erken tanı ve sonuç olarak tedavinin büyük önem taşıdığı doğumsal metabolik hastalıkların başında gelmektedir. Enzim replasman teda- visinin kullanıma girmesi ile hastalık prognozunda belirgin düzelme olmakla birlikte erken tanıya rağmen halen prognozu kötü giden hastalar bulunmaktadır. Fenotip-genotip çalışmaları bu açıdan önem taşımaktadır

Urea Cycle Disorders in Neonates: Six Case Reports

Urea cycle disorders are a group of diseases associated with hyperammonemia, which causes severe neurological sequelae, seizures and psychomotor retardation. In this study, six newborn cases diagnosed between 2010-2014 as citrullinemia Type I (four cases) and argininosuccinic aciduria (two cases) are presented in terms of clinical course and treatment responses