Mucopolysaccharidosis Type-II with Pathognomonic Skin Appearance: A Case with Pebbling Sign

Mucopolysaccharidosis type-II (MPS-II) is an X-linked lysosomal storage disorder. Here, we report an 8-year-old boy with pebbling sign in the scapular region, coarse facies, claw hand, diastolic murmur, and hepatomegaly. With decreased iduronate-2-sulfatase activity and hemizygous mutation in the IDS gene, the diagnosis was MPS-II. Pebbling sign is a rare but pathognomonic sign of MPS-II

The outcome of 41 Late-Diagnosed Turkish GA-1 Patients: A Candidate for the Turkish NBS

Background: Glutaric aciduria type 1(GA-1) is an inherited cerebral organic aciduria. Untreated patients with GA-1 have a risk of acute encephalopathic crises during the first 6 years of life. In so far as GA-1 desperately does not exist in Turkish newborn screening (NBS) program, most patients in our study were late-diagnosed. / Method: This study included 41 patients diagnosed with acylcarnitine profile, urinary organic acids, mutation analyses in the symptomatic period. We presented with clinical, neuroradiological, and molecular data of our 41 patients. / Results: The mean age at diagnosis was 14.8 13.9 (15 days to 72 months) and, high blood glutaconic acid, glutarylcarnitine and urinary glutaric acid (GA) levels in 41 patients were revealed. Seventeen different mutations in the glutaryl-CoA dehydrogenase gene were identified, five of which were novel. The patients, most of whom were late-diagnosed, had a poor neurological outcome. Treatment strategies made a little improvement in dystonia and the frequency of encephalopathic attacks. / Conclusion: All GA-1 patients in our study were severely affected since they were latediagnosed, while others show that GA-1 is a treatable metabolic disorder if it is diagnosed with NBS. This study provides an essential perspective of the severe impact on GA-1 patients unless it is diagnosed with NBS. We immediately advocate GA-1 to be included in the Turkish NBS

Clinical features of 27 Turkish Propionic acidemia patients with 12 novel mutations

Propionic acidemia (PA) is an inherited metabolic disease caused by the deficiency of one of the four biotin-dependent enzymes propionyl-CoA carboxylase (PCC), and is characterized by coma and death in unrecognized patients, additionally late diagnosis leads to severe developmental delay and neurological sequels. Manifestations of PA over time can include growth impairment, intellectual disability, seizures, basal ganglia lesions, pancreatitis, and cardiomyopathy. Other rarely reported complications include optic atrophy, hearing loss, premature ovarian insufficiency, and chronic renal failure. Mutations in PCCA-PCCB genes cause the clinically heterogeneous disease of PA. In this study, we investigate the mutation spectrum of PCCAPCCB genes and phenotypic features of 27 Turkish patients with PA from the South and Southeast parts of Turkey. We report 12 novel PA mutations, five affecting the PCCA gene and 7 affecting the PCCB gene

Niemann–Pick type C disease with a novel intronic mutation: three Turkish cases from the same family

Objectives: Niemann–Pick type C (NPC) disease is a rare progressive neurodegenerative condition that is characterized by the accumulation of cholesterol, glycosphingolipids, and sphingosine in lysosomes. Patients have various systemic and neurological findings depending on their age at onset. This disease is caused by the autosomal recessive transmission of mutations in the NPC1 and NPC2 genes; patients have mutations mainly in the NPC1 gene (95%) and the majority of them are point mutations located in the exonic regions. // Case presentation: Here, we presented three cousins with hepatosplenomegaly and progressive neurodegeneration who were diagnosed with visceral-neurodegenerative NPC disease. Their parents were relatives, and they had a history of sibling death with similar complaints. Bone marrow smear showed foamy cells in patient 1. Vertical supranuclear gaze palsy was not present in all cases. Sphingomyelinase (SM) activities were almost normal to exclude NPA or NPB. Filipin staining was performed in patient 2 and showed a massive accumulation of unesterified cholesterol The NPC1 gene analysis of the three patients showed a novel homozygous c.1553+5G>A intronic mutation. cDNA analysis was performed from the patient 3 and both parents. It was observed that exon 9 was completely skipped in the homozygous mutant baby. Both the normal and the exon 9-skipped transcripts have been detected in the parents. // Conclusions: When combined with the filipin staining and the patients’ clinical outcomes, this mutation is likely to be deleterious. Moreover, cDNA sequencing supports the pathogenicity of this novel variant

Cerrahi Maske Takan Yüzlere İlişkin Algısal Tercihler: Profesyonellerle Sıradan İnsanlar Arasında Bir Karşılaştırma

Amaç: Bu çalışmanın amacı, cerrahi maske takan bireylerin ön profil görüntülerini tamamlama konusunda ortodontistlerin ve çene cerrahlarının tercihlerini karşılaştırmak ve halktan kişilerin tercihlerini karşılaştırmaktır. Yöntemler: Çalışma, yetişkin 16 gönüllünün önden çekilmiş fotoğraflarına dayanmaktadır. Fotoğraflar cerrahi maskeli ve maskesiz olarak çekilmiştir. Açığa çıkan görüntülerde subnasal stomion mesafesi kaydedildi. Subnazal-stomion mesafesine göre stomion-yumuşak doku menton mesafesi azalan (0,4), artan (0,6) ve ideal oranlar (0,5) elde edilecek şekilde Adobe Photoshop 2021 ver. 22.5.7. Bu 3 yapay ön görüntüye ek olarak, gözbebekleri referans alınarak, MacOs yazılımı kullanılarak bir altın oran şablonuna en iyi uyacak şekilde burun, dudaklar ve menton bölgelerinin şekli değiştirilerek dördüncü bir görüntü elde edildi. Maskeli ve sentezlenmiş fotoğrafları içeren bir anket oluşturulmuş ve katılımcılardan maskenin altındaki parçanın nasıl görüneceğini seçmeleri istenmiştir. Bulgular: Halkın çoğunluğu, artan yüz oranı (%39.53) ve ardından ideal oran (%29.76) resimleri ile örtülü yüzlerin eksik kısımlarını tamamlama eğilimindeydi. Buna karşılık, profesyonellerin çoğu en çok ideal oranlı resimleri (%41,66) ve altın oranlı resimleri (%43,2) seçmiştir. Azalan yüz oranı her iki grupta da en az seçilmişti (meslekten olmayanlar tarafından %9.14, profesyoneller tarafından %2.23). Sonuçlar: Kendini ideal yüz orantılarını oluşturmaya adayan profesyonellerin çoğu, ideal orantılara sahip resimleri seçerek kapalı yüzleri tamamladı. Buna karşılık, meslekten olmayan insanlar çoğunlukla artan yüz oranını seçti. Bu çalışmada gösterilen algısal farklılıklar; mesleğin, tanıma sürecinin işleme biçimini değiştirebileceğini gösterebilir. Anahtar Kelimeler: Algısal Tercihler, Cerrahi Yüz Maskesi, Pandem

P.Val452Ile mutation of the SLC25A13 gene in a Turkish patient with citrin deficiency

PubMedID: 29376577Citrin deficiency is an autosomal recessive metabolic disorder, which is caused by pathogenic mutations in the SLC25A13 gene on chromosome 7q21.3, as the causative gene that encodes the liver type aspartate/glutamate carrier isoform 2 (AGC2). One of the main clinical presentations is neonatal intrahepatic cholestatic hepatitis caused by citrin deficiency. We report a Turkish child presented with prolonged neonatal jaundice associated with elevated plasma citrulline and galactosuria. NICCD was suspected at this point and mutation study of SLC25A13 showed that she was homozygous for the missense NM_014251.2:c.1354G>A (NP_055066.1:p. Val452Ile) (dbSNP: rs143877538) mutation. Dramatic response was observed to the dietary treatment with medium-chain triglycerides containing formula, ursodeoxycholic acid and fat-soluble vitamin supplementation. The minor allele frequency of this variant was given as nearly as 0.01 in the South Asian population; it seems like a disease causing variant. This is the first report of this variant in the Turkish and European population. © 2017, Turkish Journal of Pediatrics. All rights reserved

Impaired glucose tolerance in fanconi-bickel syndrome: Eight patients with two novel mutations

PubMedID: 29624224Fanconi-Bickel syndrome (FBS) is a rare, autosomal recessive disorder of carbohydrate metabolism caused by defects in the facilitative glucose transporter 2 (GLUT2 or SLC2A2) gene. Prominent findings are failure to thrive, renal tubular acidosis, hypoglycemia and postprandial hyperglycemia even mimicking diabetes mellitus. Eight patients from 6 families with FBS were included in this study. c.482_483insC homozygous mutation was detected in six patients from four different families. Mutation analysis of SLC2A2 gene revealed two novel homozygous mutations; c.1069delGinsAATAA and c.575A>G. Standard oral glucose tolerance test with 1.75 g/kg oral glucose was performed in six of the patients who were older than 3-years of age. Impaired glucose tolerance was found in all patients as expected and two of them had overt diabetes. None of the antidiabetic medications were given to them in order to avoid significant hypoglycemia. Beside the conservative treatment, follow up with frequent oral glucose tolerance tests are planned. We report these cases of FBS, as GSD XI is rare, two novel mutations were detected and also to highlight the risk of diabetes mellitus; although there is not a consensus about the treatment. © 2017, Turkish Journal of Pediatrics. All rights reserved

Four Gaucher disease type II patients with three novel mutations: a single centre experience from Turkey

PubMedID: 29656334Gaucher disease is the most common lysosomal storage disorder due to glucosylceramidase enzyme deficiency. There are three subtypes of the disease. Neurological involvement accompanies visceral and haematological findings only in type II and type III Gaucher patients. Type II is the acute progressive neuronopathic form which is the most severe and rare subtype. Clinical findings are recognized prenatally or in the first months of life and followed by death within the first two years of age. Among our 81 Gaucher patients, we identified 4 (4,9%) type II patients in our metabolic centre. This rate is significantly higher than the rate reported in the literature (<1%). Three of the patients had novel mutations, one of them was a collodion baby and the other one was mistyped as type III due to its atypical presentation at the beginning and he was treated with ERT for 8 months. In this report, we present our type II Gaucher patients with three novel mutations and one perinatal lethal form with generalized ichthyosis which is a very rare disorder. Additionally, we would like to highlight the phenotypic heterogeneity not only between the subtypes, also even in the same type. © 2018, Springer Science+Business Media, LLC, part of Springer Nature

Turkish case of ethylmalonic encephalopathy misdiagnosed as short chain acyl-CoA dehydrogenase deficiency

PubMedID: 29159724Ethylmalonic encephalopathy is a very rare autosomal recessively inherited inborn error of metabolism; characterized by encephalopathy, recurrent petechiae without bleeding diathesis, chronic diarrhea, and orthostatic acrocyanosis. Here, we describe a case of ethylmalonic encephalopathy with late onset neurologic symptoms and a confusing family history of two deceased brothers with the wrong suspicion of short chain acyl-CoA dehydrogenase deficiency. © 2017, Springer Science+Business Media, LLC, part of Springer Nature