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

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

Insights into the expanding phenotypic spectrum of inherited disorders of biogenic amines

Inherited disorders of neurotransmitter metabolism are rare neurodevelopmental diseases presenting with movement disorders and global developmental delay. This study presents the results of the first standardized deep phenotyping approach and describes the clinical and biochemical presentation at disease onset as well as diagnostic approaches of 275 patients from the registry of the International Working Group on Neurotransmitter related Disorders. The results reveal an increased rate of prematurity, a high risk for being small for gestational age and for congenital microcephaly in some disorders. Age at diagnosis and the diagnostic delay are influenced by the diagnostic methods applied and by disease-specific symptoms. The timepoint of investigation was also a significant factor: delay to diagnosis has decreased in recent years, possibly due to novel diagnostic approaches or raised awareness. Although each disorder has a specific biochemical pattern, we observed confounding exceptions to the rule. The data provide comprehensive insights into the phenotypic spectrum of neurotransmitter disorders

Insights into the expanding phenotypic spectrum of inherited disorders of biogenic amines

Inherited disorders of neurotransmitter metabolism are rare neurodevelopmental diseases presenting with movement disorders and global developmental delay. This study presents the results of the first standardized deep phenotyping approach and describes the clinical and biochemical presentation at disease onset as well as diagnostic approaches of 275 patients from the registry of the International Working Group on Neurotransmitter related Disorders. The results reveal an increased rate of prematurity, a high risk for being small for gestational age and for congenital microcephaly in some disorders. Age at diagnosis and the diagnostic delay are influenced by the diagnostic methods applied and by disease-specific symptoms. The timepoint of investigation was also a significant factor: delay to diagnosis has decreased in recent years, possibly due to novel diagnostic approaches or raised awareness. Although each disorder has a specific biochemical pattern, we observed confounding exceptions to the rule. The data provide comprehensive insights into the phenotypic spectrum of neurotransmitter disorders.We thank all patients and their families for their contributions to this study and for their trust. T.H. and J.K. were supported the grant from the Ministry of Health of the Czech Republic RVO-VFN 64165 GJIH-0599-00-7-846 and ProgresQ26/LF1. A.G.C. and N.J.P. are supported by FIS P118/00111 “Instituto de Salud Carlos III (ISCIII)” and “Fondo Europeo de desarrollo regional (FEDER)”. T.O., K.J., G.F.H. and O.K.H. were supported in parts by the Dietmar Hopp Foundation, St. Leon-Rot, Germany. M.A.K. is funded by an NIHR Professorship, the Sir Jules Thorn Award for Biomedical Research and the Rosetrees trust. M.V. is supported by Stichting Stofwisselkracht Grant. D.H. acknowledges funding by the Molecular Diagnostics Program of the National Center for Tumor Diseases (NCT) Heidelberg.Peer reviewe

A possible biomarker of neurocytolysis in infantile gangliosidoses: aspartate transaminase

PubMedID: 30712135Gangliosidoses (GM1 and GM2 gangliosidosis) are rare, autosomal recessive progressive neurodegenerative lysosomal storage disorders caused by defects in the degradation of glycosphingolipids. We aimed to investigate clinical, biochemical and molecular genetic spectrum of Turkish patients with infantile gangliosidoses and examined the potential role of serum aspartate transaminase levels as a biomarker. We confirmed the diagnosis of GM1 and GM2 gangliosidosis based on clinical findings with specific enzyme and/or molecular analyses. We retrospectively reviewed serum aspartate transaminase levels of patients with other biochemical parameters. Serum aspartate transaminase level was elevated in all GM1 and GM2 gangliosidosis patients in whom the test was performed, along with normal alanine transaminase. Aspartate transaminase can be a biochemical diagnostic clue for infantile gangliosidoses. It might be a simple but important biomarker for diagnosis, follow up, prognosis and monitoring of the response for the future therapies in these patients. © 2019, Springer Science+Business Media, LLC, part of Springer Nature

Congenital erythropoietic porphyria with erythrodontia: A case report

PubMedID: 30706587Background: The causes for intrinsic tooth discoloration can be separated into two categories as systemic and local. Systemic causes are either genetic or drug-induced effects. The development of dentition can also be affected by a number of systemic factors and metabolic diseases such as porphyria. Congenital erythropoietic porphyria (CEP), also known as Gunther's disease, is a metabolic disease caused by a transformation in the gene that codifies uroporphyrinogen-3 synthesis, leading to porphyrin aggregation in urine, skin, bone, and dentin. Case Report: A 21-month-old girl with erythrodontia was referred to Paediatric Dentistry Department in September 2017. A physical examination revealed blisters on her face, nose, hands, and feet. Laboratory findings showed highly elevated urine total uroporphyrin and total coproporphyrin I and III levels. Next-generation sequencing multigene panel testing for porphyria demonstrated a homozygous c.10C>T (p.L4F) mutation in the UROS gene. For curative therapy, the patient was admitted to the allogeneic bone marrow transplantation program. Conclusion: Congenital erythropoietic porphyria most commonly presents in the first few years of life. Manifestations can include reddish-colored urine, skin blistering, scarring, and erythrodontia. A timely diagnosis can prevent undesirable skin findings of the disease and death due to hematological involvement before a curative allogeneic bone marrow transplantation is performed. © 2019 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Lt

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

Cross-cultural adaptation, validity, and reliability of the Turkish version of Assistance to Participate Scale.

BACKGROUND: The Assistance to Participate Scale is a questionnaire to evaluate activity participation of children with developmental disabilities. The purpose of this study was to determine the validity and reliability of the Turkish version of the Assistance to Participate Scale. METHODS: Ninety-eight mothers' children with developmental disabilities were included in this study. The Assistance to Participate Scale, Pediatric Quality of Life Inventory, and Pediatric Evaluation of Disability Inventory were applied to all subjects. To evaluate reliability, Cronbach's alpha coefficient, minimal detectable change (MDC) with standard error of measurement (SEM), and intraclass correlation coefficient (ICC) for test-retest were used. The relationship between Assistance to Participate Scale, Pediatric Quality of Life Inventory, and Pediatric Evaluation of Disability Inventory was investigated, and exploratory and confirmatory factor analysis were used for construct validity. RESULTS: Cronbach's alpha value of the scale was found.93, demonstrating that this value has excellent internal consistency. Test-retest reliability was found 0.99 (ICC 95% CI [0.995, 0.998]; SEM:0.57, MDC:1.58). For construct validity, the correlations between Assistance to Participate Scale, Pediatric Quality of Life Inventory, and Pediatric Evaluation of Disability Inventory total scores and items were significant (p < .001). Factor analysis showed that the questionnaire had unidimensional and the explained variance was 0.84%. CONCLUSIONS: The Turkish version of the Assistance to Participate Scale is valid and reliable scale for children with developmental disabilities