Browsing by Author "Aydin, Halil Ibrahim"

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Bi-Allelic Loss-Of-Function OBSCN Variants Predispose Individuals to Severe Recurrent Rhabdomyolysis
(2021) Aydin, Halil Ibrahim; https://orcid.org/0000-0001-7994-4394; 34957489; AHD-1839-2022
Rhabdomyolysis is the acute breakdown of skeletal myofibres in response to an initiating factor, most commonly toxins and over exertion. A variety of genetic disorders predispose to rhabdomyolysis through different pathogenic mechanisms, particularly in patients with recurrent episodes. However, most cases remain without a genetic diagnosis. Here we present six patients who presented with severe and recurrent rhabdomyolysis, usually with onset in the teenage years; other features included a history of myalgia and muscle cramps. We identified 10 bi-allelic loss-of-function variants in the gene encoding obscurin (OBSCN) predisposing individuals to recurrent rhabdomyolysis. We show reduced expression of OBSCN and loss of obscurin protein in patient muscle. Obscurin is proposed to be involved in sarcoplasmic reticulum function and Ca2+ handling. Patient cultured myoblasts appear more susceptible to starvation as evidenced by a greater decreased in sarcoplasmic reticulum Ca2+ content compared to control myoblasts. This likely reflects a lower efficiency when pumping Ca2+ back into the sarcoplasmic reticulum and/or a decrease in Ca2+ sarcoplasmic reticulum storage ability when metabolism is diminished. OSBCN variants have previously been associated with cardiomyopathies. None of the patients presented with a cardiomyopathy and cardiac examinations were normal in all cases in which cardiac function was assessed. There was also no history of cardiomyopathy in first degree relatives, in particular in any of the carrier parents. This cohort is relatively young, thus follow-up studies and the identification of additional cases with bi-allelic null OBSCN variants will further delineate OBSCN-related disease and the clinical course of disease. Cabrera-Serrano et al. show that biallelic loss-of-function variants in the gene encoding obscurin (OBSCN) predispose individuals to recurrent and severe episodes of rhabdomyolysis, typically with onset in the teenage years.
Chronic Enteropathy Associated with SLCO2A1 Gene and Hereditary Fructose Intolerance: A Coincidence of Two Rare Diseases
(2022) Donger, Utku; Warasnhe, Khaled; Ozcay, Figen; Haskologlu, Zehra Sule; Aydin, Halil Ibrahim; Ceylaner, Serdar; https://orcid.org/0000-0002-5214-516X; https://orcid.org/0000-0001-7994-4394; 36384942; ABG-5684-2020; AHD-1839-2022
Chronic enteropathy associated with SLCO2A1 gene (CEAS) is a rare disorder characterized by multiple small intestine ulcers. Patients with CEAS typically present with chronic anemia and gastrointestinal bleeding. Besides CEAS, SLCO2A1 mutations cause primary hypertrophic osteoarthropathy (PHO) which is considered as an extraintestinal manifestation in CEAS patients. Since CEAS and Crohn's disease are clinically indistinguishable, patients are often misdiagnosed with Crohn's disease. Herein, we describe a 4-year-old Turkish girl with CEAS due to homozygous pathogenic variant (c.656C > T) in SLCO2A1 with concomitant hereditary fructose intolerance (HFI) caused by homozygous pathogenic variant (c.1005C > G) in ALDOB. Prompt restriction of fructose, sucrose and sorbitol resulted in hepatomegaly regression and mild amelioration of patient's symptoms. Despite budesonide and azathioprine treatments, patient's protein losing enteropathy and chronic anemia did not improve. Although previous CEAS cases were reported from East Asian countries, it is likely to occur in people from other geographic areas. CEAS seems to be underdiagnosed and high index of suspicion is required for the diagnosis of this rare entity. Patients with prior diagnosis of Crohn's disease with no response to immunosuppressive treatment or anti-TNF therapy should be re-evaluated for possible CEAS diagnosis.
Coexistence of guanidinoacetate methyltransferase (GAMT) deficiency and neuroleptic malignant syndrome without creatine kinase elevation
(2020) Ayanoglu, Muge; Korgali, Elif; Sezer, Taner; Aydin, Halil Ibrahim; Sonmez, Fatma Mujgan; 0000-0002-2278-1827; 0000-0001-7994-4394; 32173091; AAJ-5931-2021
We describe the first child with guanidinoacetate methyltransferase (GAMT) deficiency who developed neuroleptic malignant syndrome (NMS) after the treatment of risperidone without elevated creatine kinase (CK) levels. The patient presented with lethargy, hyperthermia, generalized tremor and rigidity with normal serum CK levels. After cessation of risperidone and adding clonezepam to the supportive treatment, symptoms of NMS were ameliorated. We conclude that although serum CK elevation is a useful indicator for the early detection of NMS, normal serum CK levels may be seen during the NMS course in the presence of GAMT deficiency. (C) 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Creatine Transporter Deficiency in Two Brothers with Autism Spectrum Disorder
(2018) Aydin, Halil Ibrahim; 0000-0001-7994-4394; 29396939
Creatine transporter deficiency (CTD) is a treatable, X-linked, inborn error of metabolism. Two brothers with autism spectrum disorder were diagnosed with CTD at the ages of 17 and 12 years. Both were found to have a previously reported hemizygous p.408delF (c.1216_1218delTTC) deletion mutation. Both patients were given creatine monohydrate, L-arginine, L-glycine and S-adenosylmethionine, which partially improved the behavioral problems. Serum creatinine levels, creatine peak at brain MR spectroscopy or creatine/creatinine ratio in urine should be evaluated to identify CTD in children with autistic behavior and language disorders.
Genetic Studies in Autism: Correspondence
(2017) Aydin, Halil Ibrahim; 0000-0001-7994-4394; 27506425; AHD-1839-2022
A novel mutation in TRMT5 associated with idiopathic non-cirrhotic portal hypertension and hepatopulmonary syndrome: Case report of two siblings
(2022) Warasnhe, Khaled; Ozcay, Figen; Aydin, Halil Ibrahim; Ozgun, Gonca; Ceylaner, Serdar; https://orcid.org/0000-0002-0781-5814; 35460901
Non-cirrhotic portal hypertension (NCPH) is a rare clinical entity in children. Familial clusters of idiopathic non-cirrhotic portal hypertension (INCPH) were previously reported in cases with deoxyguanosine kinase (DGOUK) and potassium calcium-activated channel subfamily N member 3 (KCNN3) mutations. Herein, we report two siblings who had a novel mutation in mitochondrial tRNA methyltransferase 5 (TRMT5) gene and presented with hepatopulmonary syndrome and later diagnosed as INCPH. Autosomal recessive inheritance of this mutation may suggest a role of TRMT5 mutations in the development of NCPH. Screening of TRMT5 mutations could be considered when familial INCPH is suspected. ?? 2022 Elsevier Masson SAS. All rights reserved.
A novel mutation in two cousins with guanidinoacetate methyltransferase (GAMT) deficiency presented with autism
(2019) Aydin, Halil Ibrahim; Sonmez, Fatma Mujgan; 0000-0001-7994-4394; 31559727
Guanidinoacetate methyltransferase (GAMT) deficiency is a rare autosomal recessive disorder of creatine biosynthesis. Here, we report 9 and 10-year-old cousins with GAMT deficiency caused by a novel mutation who both exhibited neurodevelopmental retardation, seizures, behavioral problems, and autism that began during early infancy. The patients were diagnosed as having only autism and followed for years without a specific diagnosis although they had very low levels of serum creatinine for several times. A novel nonsense mutation in the GAMT gene that caused cessation of synthesis of the protein encoded by this gene was identified in these patients. GAMT deficiency is a treatable inborn error of metabolism and should be considered for all patients with hypotonia, developmental delay, seizures and autism, particularly if low serum creatinine levels are observed.
Pediatric Liver Transplantation Indications and Outcomes in Glycogen Storage Disease: A Single Center Experience
(2022) Ozcay, Figen; Kar, Hazel Delal Dara; Warasnhe, Khaled; Aydin, Halil Ibrahim; Akdur, Aydincan; Haberal, Mehmet; 0000-0002-5214-516X; 0000-0002-3462-7632; 0000-0001-7994-4394; ABG-5684-2020; AAJ-8097-2021; AHD-1839-2022
Severe isolated sulfide oxidase deficiency with a novel mutation
(2021) Ergene, Merit; Yarar, Nuriye; Oncel, Elif Perihan; Sezer, Taner; Cavdarli, Busranur; Ecevit, Ismail Zafer; Aydin, Halil Ibrahim; 0000-0002-6126-4048; 34449156; AAK-4837-2021; AHD-1839-2022
Background. Isolated sulfite oxidase deficiency (ISOD), caused by mutations in SUOX gene, is an autosomal recessive disease manifesting with early onset seizures, developmental delay, microcephaly, and spasticity. It mimics hypoxic-ischemic encephalopathy (HIE) in the neonatal period and is characterized by progressive severe neurological impairment due to accumulation of toxic metabolites. Case. This report presents a late diagnosed male patient with ISOD manifesting with neonatal-onset seizures, developmental delay, microcephaly, and spastic quadriplegia. Brain magnetic resonance imaging of the patient showed bilateral subcortical multi-cystic encephalomalacia involving bilateral parieto-occipital regions. A novel homozygous c.590_595delAGCCTC in-frame deletion in SUOX gene was identified in the patient, while both parents were heterozygous for that mutation. Conclusion. The mutation identified in our patient causes severe ISOD. Early diagnosis of ISOD is essential for accurate genetic counseling and achieving prenatal diagnosis. Screening for urinary sulfite in patients with neonatal or early infantile onset seizures, developmental delay, microcephaly and cystic encephalomalacia in neuroimaging mimicking HIE helps in early diagnosis.
Three-Country Snapshot of Ornithine Transcarbamylase Deficiency
(2022) Aydin, Halil Ibrahim; https://orcid.org/0000-0001-7994-4394; 36362876
X-linked ornithine transcarbamylase deficiency (OTCD) is the most common urea cycle defect. The disease severity ranges from asymptomatic carrier state to severe neonatal presentation with hyperammonaemic encephalopathy. We audited the diagnosis and management of OTCD, using an online 12-question-survey that was sent to 75 metabolic centres in Turkey, France and the UK. Thirty-nine centres responded and 495 patients were reported in total. A total of 208 French patients were reported, including 71 (34%) males, 86 (41%) symptomatic and 51 (25%) asymptomatic females. Eighty-five Turkish patients included 32 (38%) males, 39 (46%) symptomatic and 14 (16%) asymptomatic females. Out of the 202 UK patients, 66 (33%) were male, 83 (41%) asymptomatic and 53 (26%) symptomatic females. A total of 19%, 12% and 7% of the patients presented with a neonatal-onset phenotype in France, Turkey and the UK, respectively. Vomiting, altered mental status and encephalopathy were the most common initial symptoms in all three countries. While 69% in France and 79% in Turkey were receiving protein restriction, 42% were on a protein-restricted diet in the UK. A total of 76%, 47% and 33% of patients were treated with ammonia scavengers in Turkey, France and the UK, respectively. The findings of our audit emphasize the differences and similarities in manifestations and management practices in three countries.