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Seizures in newborn infants may be the first finding of hereditary metabolic diseases. Pyridoxine-dependent epilepsy (PDE) is a treatable disorder associated with defects in the one of ALDH7A1, PNPO, or PLPBP genes and it is uncommon but progresses with persistent seizures in the neonatal and infancy period. The seizures are generally resistant to traditional antiepileptic drugs and show a dramatic response to high-dose pyridoxine. In 2016, mutations were reported in PLPBP (previously known as PROSC) gene, which encodes pyridoxal phosphate homeostatic protein (PLPHP).When early-onset antiepileptic resistant seizures are not treated, clinical findings emerge including the development of encephalopathy, congenital microcephaly, and subsequent retardation of psychomotor development. The present case is a 33-month-old female infant with seizures starting from postnatal day 1, who did not respond to traditional anti-epileptic drugs but responded to pyridoxine treatment. In the genetic tests, homozygote c.695 C T (p.Ala232Val) mutation was determined in the PLPBP gene, which has not been previously identified. Since a specific treatment was found, this case is reported with the aim of emphasizing the need to consider pyridoxine dependence, which is one of the vitamin-dependent metabolic encephalopathies, in the differential diagnosis of epilepsy patients.

This study aimed to evaluate the relationship between clinical findings, height and weight standard deviation scores, 25-hydroxyvitamin D25(OH)DIn total, 67.5% patients had a short stature, and 50% of them were underweight for their age. Of the patients, 13.5% were immobile, 28.6% had 25(OH)DThe low BMD z score prevalence reported with DXA was misleadingly higher in children with MPS and short stature. To prevent exposure to unnecessary antiresorptive treatments in these children, the effect of severe short stature and bone geometry on DXA measurements should be considered; further studies on bone health are warranted.

Herediter tirozinemi tip-1 (HT1), fumarilasetoasetat hidrolaz enzim eksikliğine bağlı, nadir görülen hepatorenal bir kalıtsal metabolik hastalıktır. Herediter tirozinemi tip-1 yönetiminde, tirozin ve fenilalaninden kısıtlı diyetle birlikte nitisinon tedavisi kullanılması önerilmektedir. Otoimmün diyabet olarak da bilinen Tip-1 Diabetes Mellitus (T1DM), pankreas β-hücre disfonksiyonuna bağlı mutlak insülin eksikliği ile karakterize ve hiperglisemiye yol açan kronik endokrinolojik bir hastalıktır. Hastalarda glisemik kontrolü sağlamak için insülin ile birlikte beslenme tedavisi ve uygun fiziksel aktivite önemli yer tutmaktadır. Literatürde sınırlı sayıda olguda HT1 ve T1DM birlikteliği tanımlanmıştır. Bu sunumda tirozin metabolizma bozukluklarından HT1 nedeniyle izlenirken T1DM gelişen bir olgunun diyet yönetimi ve izlem süreci paylaşılmıştır. Yoğun insülin tedavisi ile fenilalanin ve tirozinden kısıtlı diyet tedavisi iki hastalık birlikteliğinde başarılı bir şekilde yönetilmiştir.

Cystinosis is a lysosomal storage disease that affects many tissues. Its prognosis depends predominantly on kidney involvement. Cystinosis has three clinical forms: nephropathic infantile, nephropathic juvenile and non-nephropathic adult. Proximal tubular dysfunction is prominent in the infantile form, whereas a combination of glomerular and tubular alterations are observed in the juvenile form. Thirty-six children with nephropathic cystinosis were included in the study. Clinical features, molecular genetic diagnoses, and kidney outcomes of the patients were evaluated. Twenty-one children (58.3%) were male. The median age at diagnosis was 18.5 months. Twenty-eight patients (77.8%) had infantile nephropathic cystinosis, while eight (22.2%) had juvenile nephropathic cystinosis. An acute rapid deterioration of the kidney function with proteinuria, hypoalbuminemia, and nephrotic syndrome, was observed in 37.5% of patients with the juvenile form. The mean estimated glomerular filtration rate (eGFR) was 82.31 ± 37.45 ml/min/1.73m2 at diagnosis and 63.10 ± 54.60 ml/min/1.73m2 at the last visit (p = 0.01). Six patients (16.6%) had kidney replacement therapy (KRT) at the last visit. The median age of patients with kidney failure was 122 months. Patients with a spot urine protein/creatinine ratio G (32.6%). The patients with the most common mutation tended to have higher mean eGFR and lower leukocyte cystine levels than patients with other mutations. Glomerulonephritis may be a frequent finding in addition to the well-known tubular dysfunction in patients with cystinosis. Furthermore, our results highlight that the presence of severe proteinuria at the time of diagnosis is a relevant prognostic factor for kidney survival.

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.

Amaç: Beta-ketotiolaz (T2) ve suksinil-KoA:3-ketoasit KoA transferaz (SCOT) keton cisimlerinin yıkımında görev alan iki enzimdir. Ketolizde görevli bu iki enzimin eksikliğinde erken çocuklukta açlık veya diğer katabolik süreçlerle tetiklenen ve tekrarlayan ketoasidoz atakları görülür. Bu çalışmada, ketoliz defekti tanısıyla izlenen hastaların klinik ve moleküler özelliklerinin incelenmesi amaçlandı. Yöntem: Çukurova Üniversitesi Çocuk Metabolizma ve Beslenme Bilim Dalı’nda takipli 15 T2 eksikliği ve bir SCOT eksikliği tanılı hasta çalışmaya dahil edildi. Geriye dönük hastaların tıbbi kayıtları incelendi. Bulgular: Hastaların sekizi kız, sekizi erkekti. 13 hastada anne-baba akrabalığı, 11 hastada aile öyküsü vardı. SCOT eksikliği olan hastanın ilk ketoasidoz atağı iki günlükken olmuştu. T2 eksikliği olan hastalarda ise ilk atak yaşı ortalama 8,0±6,7 aydı (4 gün-29 ay). SCOT eksikliği olan hastanın atakları arasında hem negatif hem pozitif aseton değerleri olması ilginç özelliğiydi. T2 eksikliği tanılı hastaların tümünde atak dışında keton hep negatifti. Atak sırasında 10 hastada hipoglisemi, altısında ise hiperglisemi görüldü. Hastaların izlem süresince ortalama atak sayısı 3,8±3,1 idi. Hastalardan tanı ve ayırıcı tanı için açilkarnitin profili ve organik asit analizi çalışıldı. Mutasyon analizi yapılabilen 11 hastadan 10’unda bulunan mutasyonlar literatürde ilk kez bu çalışmayla tanımlandı. Sonuç: Ketoasidoz tablosunda gelen hastalarda organik asidemi ayırıcı tanısında daha nadir görülseler de ketoliz defektlerinin akılda tutulması gereklidir. Organik asidemilerden farklı olarak hastaların çoğunda kan şekeri ve beslenme durumundan bağımsız süreğen ketozisin olması, tipik organik asit ve açilkarnitin profili en önemli tanısal ipuçlarıdır. Bu gruptaki iki hastalığın tedavileri organik asidemiler kadar ciddi ve süreğen protein kısıtlaması ve kofaktör desteği gerektirmediğinden hem hastaların büyümelerini hem de yaşam kalitelerini daha az etkilemektedir.

Amaç: Bu çalışmada farklı tiplerinde değişen oranlarda multisistemik tutuluma, nörolojik bulguların da eşlik ettiği mukopolisakkaridozlu hastalarda, serum vitamin B12 düzeylerinin de klinik seyir üzerine etkisi araştırılmıştır.Gereç ve Yöntem: Bu çalışmaya enzim düzeyi ve mutasyon analizi ile mukopolisakkaridoz tanısı konulan 114 hasta çalışmaya dahil edildi. Bu hastalardan periyodik takipleri sırasında sistemik ve nörolojik değerlendirmeye ek olarak serum vitamin B12 düzeyleri ölçüldü. Vitamin B12 düzeyi

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 late-diagnosed, 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.

Objectives Aldolase A deficiency also known as glycogen storage disease (GSD) XII, is an ultra rare autosomal recessively inherited GSD, associated with hemolytic anemia and rhabdomyolysis. Case presentation Here, we first report a patient with dermatological findings, hemodialysis requirement for rhabdomyolysis, and a novel likely pathogenic c.971C>T (p.A324V) mutation in the ALDOA gene. Conclusions Episodes of rhabdomyolysis can be triggered by febrile illnesses and catabolic processes. Diagnosis should be confirmed by the mutation analysis of ALDOA gene. Treatment includes management of hemolytic anemia and administration of antipyretics during febrile episodes to avoid hemolysis and rhabdomyolysis.

Objective: Monogenic diabetes is a heterogeneous disease that causes functional problems in pancreatic beta cells and hyperglycemia. The aim of this study was to determine the clinical and laboratory features, the admission characteristics and distribution of monogenic form of diabetes in childhood in Turkey. Methods: Patients aged 0-18 years, who were molecularly diagnosed with monogenic diabetes, and consented to participate, were included in the study. Results: Seventy-seven (45.6\%) female and 92 male cases with a mean age of 8.18 +/- 5.05 years at diagnosis were included. 52.7\% of the cases were diagnosed with monogenic diabetes by random blood glucose measurement. The reason for genetic analysis in 95 (56.2\%) of cases was having a family member diagnosed with diabetes under the age of 25. At the time of diagnosis, ketone was detected in urine in 16.6\% of the cases. Mean hemoglobin A1c on admission, fasting blood glucose, fasting insulin, and c-peptide values were 7.3 +/- 2.1\%, 184.9 +/- 128.9 mg/dL, 9.4 +/- 22.9 IU/L, 1.36 +/- 1.1 and ng/L respectively. GCK-MODY was found in 100 (59.2\%), HNF1A-MODY in 31 (18.3\%), and variants in ABCC8 in 6 (3.6\%), KCNJ11 in 5 (3\%), HNF4A in 2 (1.2\%), and HNF1B in 2 (1.2\%). Conclusion: Recent studies have indicated HNF1A-MODY is the most frequent of all the MODY-monogenic diabetes cases in the literature (50\%), while GCK-MODY is the second most frequent (32\%). In contrast to these reports, in our study, the most common form was GCK-MODY while less than 20\% of cases were diagnosed with HNF1A-MODY.

Metabolites like lipids, amino acids or peptides can affect the immune system. Citrulline is an amino acid that activates several inflammatory pathways. Serum citrulline levels are markedly elevated in hereditary citrullinemia type 1 (CTLN1), and cases with CTLN1 have have been described with inflammatory lesions of the central nervous system (CNS). This suggests the presence of a relatively proinflammatory state in CTLN1. We therefore tested sera of CTLN1 patients for anti-myelin oligodendrocyte glycoprotein (MOG) antibodies which are a frequent cause of inflammatory CNS disorders in young patients. Patients with CTLN1 (n = 15) and control groups consisting of phenylketonuria (n = 22), juvenile idiopathic arthritis (n = 13), pediatric onset systemic lupus erythematosus (n = 17) and healthy controls (n = 48) were tested for serum anti-MOG IgG and anti-MOG IgG1 antibodies in a live-cell based assay. Serum citrulline levels were elevated in 14/15 CTLN1 patients at the time of the study. No clear anti-MOG IgG positivity was detected in any of the CTLN1 or control groups. One CTLN1 and one healthy control case with anti-MOG IgG titers close to borderline were also tested for MOG-specific IgG1, with similar results. These findings did not support the role of elevated serum citrulline levels in facilitating antibody response against MOG. Other pathways that can be investigated in CTLN1 include lymphocytic responses against neural antigens or any direct effects of citrulline on neural tissue.

Osteogenez İmperfekta, birçok fenotipe sahip, nadir görülen kalıtsal bir kemik metabolizması hastalığıdır. Tip I kollajen yapımından sorumlu genlerdeki mutasyonlar sonucunda oluşur. Hem otozomal dominant hem de otozomal resesif geçişli bu hastalıkta, vakaların %80'inden fazlası en yaygın COL1A1 ve COL1A2 genlerindeki mutasyonlarla ilişkilidir. IFITM5 genindeki mutasyonlar ise vakaların %5-10'undan sorumludur. IFITM5 geninde görülen en yaygın mutasyon “c. - 14C> T”, otozomal dominant Osteogenez İmperfekta Tip V'den sorumludur. Osteogenez İmperfekta Tip V’in klinik varyasyonu çoktur. Bazı durumlarda fenotipik özelliklerin zayıf olması tanıyı daha da zorlaştırır. Bu olgu sunumu hem hastanemizde ilk tanı konulan Osteogenez İmperfekta Tip V olgusu olması hem de klinik özelliklerinin farklı olması nedeniyle sunulmuştur., Osteogenesis Imperfecta (OI) is a rare hereditary disease of bone metabolism which has many phenotypes. It occurs as a result of mutations in genes responsible for making Type I collagen. In this disease with both autosomal dominant and recessive inheritance, more than 80% of cases are associated with mutations in COL1A1-A2 genes. In the rest, mutations in the IFITM5 gene are responsible for 5-10% of the cases. The most common mutation seen in IFITM5 gene “c. - 14C> T ” is responsible for autosomal dominant OI Type V. There are many clinical variations of OI type V. The fact that the poor phenotypic features in some cases make the diagnosis more difficult. This case report was presented because of both being the first OI Type V case diagnosed in our hospital and differences of its clinical features.

Galaktozemi, otozomal resesif olarak kalitilan, karbonhidrat metabolizmasinin nadir bir hastaligidir. En sik gorulen formu klasik galaktozeminin nedeni galaktoz-1-fosfat-uridil transferaz enzim eksikligidir. Situs inversus totalis; torasik ve abdominal solid organlarin komplet transpozisyonunu tanimlayan baska bir nadir konjenital durumdur. Yenidogan doneminden itibaren galaktozemi tanisiyla izlenen bir hastada 10 yasina geldiginde ayrintili bir fizik muayene sayesinde situs inversus totalis anomalisi saptandi ve radyolojik olarak dogrulandi. Iki nadir ve birbiri ile iliskisiz kalitsal ve konjenital hastaligin birlikteligini daha once hic bildirilmedigi icin ilginc bularak sunmak ve ayrintili bir fizik muayenenin onemine bir kez daha dikkat cekmek istedik.

Background/aim Isolated methylmalonic acidemia (MMA) is caused by complete or partial deficiency of the enzyme methylmalonyl-CoA mutase (mut0 or mut– enzymatic subtype), a defect of its cofactor adenosyl-cobalamin (cblA, cblB, or cblD-MMA), or deficiency of the enzyme methylmalonyl-CoA epimerase. While onset of the disease ranges from the neonatal period to adulthood, most cases present with lethargy, vomiting and ketoacidosis in the early infancy. Major secondary complications are; growth failure, developmental delay, interstitial nephritis with progressive renal failure, basal ganglia injury and cardiomyopathy. We aimed to demonstrate clinical and molecular findings based on long-term follow up in our patient cohort. Materials and methods The study includes 37 Turkish patients with isolated MMA who were followed up for long term complications 1 to 14 years. All patients were followed up regularly with clinical, biochemical and dietary monitoring to determine long term complications. Next Generation Sequencing technique was used for mutation screening in five disease-causing genes including; MUT , MMAA , MMAB , MMADHC , MCEE genes. Mutation screening identified 30 different types of mutations. Results While 28 of these mutations were previously reported, one novel MMAA mutation p.H382Pfs*24 (c.1145delA) and one novel MUT mutation IVS3+1G>T(c.752+1G>T) has been reported. The most common clinical complications were growth retardation, renal involvement, mental motor retardation and developmental delay. Furthermore, one of our patients developed cardiomyopathy, another one died because of hepatic failure and one presented with lactic acidosis after linezolid exposure. Conclusion We have detected two novel mutations, including one splice-site mutation in the MUT gene and one frame shift mutation in the MMAA gene in 37 Turkish patients. We confirm the genotype-phenotype correlation in the study population according to the long-term complications.

WOS: 000436882600003 Aim: Alkaptonuria (AKU) is an autosomal recessively inherited disease caused by a deficiency of homogentisate 1,2-dioxygenase. This enzyme converts homogentisic acid (HGA) into maleylacetoacetic acid in the tyrosine degradation pathway. The presence of HGA in urine, ochronosis (bluish-black pigmentation in connective tissues) and arthritis of the spine and the other large joints are the three major features of AKU. Nitisinone and a tyrosine-restricted diet are the treatment options. in this study, we evaluated the demographic and clinical characteristics and also the mutations of our AKU patient. Materials and Methods: This retrospective single centre study included 36 patients who were diagnosed as AKU between the years of 2002 and 2017 Cukurova University Faculty of Medicine, Department of Pediatrics, Division of Metabolism and Nutrition. Results: Thirty six AKU patients were included (17 female, 19 male) in our study. The mean age of the patients was 9.3 +/- 13.4 years (3 months-54 years). The major complaints were darkening of the urine (100%), ochronosis (11.1%), arthralgia (16.7%) and arthritis (8.1%). Darkening of the urine was firstly recognized at the age of 8.89.+/- 16.9 months (1-84 months). Eighteen (86%) patients had homozygous and 3(14%) patients had compound heterozygous mutations in the HGD gene. Conclusion: AKU was the first inherited metabolic disease defined. The three main features are; darkening of the urine at birth wich is followed by ochronosis (blue-dark pigmentation) clinically visible in the ear and alae of the nose and finally a severe ocbronotic arthropathy of the spine and large joints at around the age of 50 years. Here we report on the clinical and genetic features of our patients at various ages.

Background: Biotinidase deficiency (BD) is an autosomal recessive inborn error of metabolism characterized by neurologic and cutaneous symptoms and can be detected by newborn screening. Newborn screening for BD was implemented in Turkey at the end of 2008. Methods: In total, 203 patients who were identified among the infants detected by the newborn screening were later confirmed to have BD through measurement of serum biotinidase activity. We also performed BTD mutation analysis to characterize the genetic profile. Results: Twenty-seven mutations were identified. The most commonly found variants were c.1330G>C (p.D444H), c.1595C>T (p.T532M), c.470G>A (p.R157H), and c.198_104delGCGGCTGinsTCC (p.C33Ffs ) with allele frequencies of 0.387, 0.175, 0.165 and 0.049, respectively. Three novel pathogenic and likely pathogenic variants were identified: p.W140* (c.419G>A), p.S319F (c.956C>T) and p.L69Hfs*24 (c.192_193insCATC). We also identified three mutations reported in just one patient in the past (p.V442Sfs*59 [c.1324delG], p.H447R [c.1340A>G] and p.198delV [c.592_594delGTC]). Although all of the patients were asymptomatic under the treatment of biotin, only one patient, who had the novel c.419G>A homozygous mutation became symptomatic during an episode of acute gastroenteritis with a presentation of ketosis and metabolic acidosis. Among the screened patients, 156 had partial and 47 had profound BD. Conclusions: We determined the mutation spectra of BD from the southeastern part of Turkey. The results of this study add three more mutations to the total number of mutations described as causing BD.

WOS: 000436882600013 Typical features of Netherton syndrome are congenital ichthyosiform erythroderma, atopic diathesis and trichorrhexis nodosa.Here in this report, we present a case with congenital ichthyosis with atopy presenting later. We wanted to discuss the importance of whole exome sequencing to diagnose the atypical presentations of common syndromes.

Introduction Fanconi Bickel Syndrome (FBS) is a rare autosomal recessively inherited inborn error of metabolism due to impaired utilization of glucose and galactose. The mutations of the responsible gene SLC2A2 cause defects in glucose transport protein-2. Clinical findings are severe growth retardation, polyuria, polydipsia, and hypophosphatemic rickets. Laboratory findings are proximal renal tubular dysfunction, fasting hypoglycemia and postprandial hyperglycemia leading to diabetes, in some cases even in the neonatal period, due to hepatorenal glycogen accumulation. Method Data of 10 patients from 8 families diagnosed as FBS with molecular analysis were reviewed retrospectively for renal involvement. Results 3(30%) were female and 7(70%) were male. All had parental consanguinity. Mean age at diagnosis was 10,8±8,5 months. Mean current age was 7,3 ± 6 years. One patient died at 1 year of age. Height measurements of 7 patients were below 3rd percentile and weight measurements of all patients were below 3rd percentile. 6 patients (60%) had hepatomegaly. Hypertransaminasemia, hypertriglyceridemia and metabolic acidosis with normal anion gap were observed in all patients. 9(90%) patients had hypophosphatemia, hypokalemia and 6(60%) patients had hyponatremia. All patients had glycosuria and proteinuria. Tubular phosphate reabsorption levels of 4 out of 8 patients were below 78%. Mean HbA1C levels were 5,6±0,6, oral glucose tolerance test was performed on 6 patients over three years of age. Plasma glucose levels at 120 minutes were higher than 140 mg/dL in 4 (66,7%), higher than 200 mg/dL in 2 patients (33,3%)despite none of them had overt diabetes. 8 patients (80%) showed severe manifestations of rickets. All patients had homozygous SLC2A2 gene mutations [6 had p.G162Rfs*17(c.482_483insC), 1 had p.H192R(c.575A>G), 1 had p.R301*(c.901C>T), 1 had p.D344Y(c.1030G>T), 1 had p.V357Nfs*37(c.1069delGinsAATAA)] Discussion FBS is a well-defined and a very rare inherited metabolic disease characterized with hepatic and renal involvement. Here, we report our single center experience of 10 patients with FBS, due to the high frequency of parental consanguinity in our region. Different from the other glycogen storage diseases and disorders of carbohydrate metabolism such as galactosemia and hereditary fructose intolerance, hyperglycemia is an important factor contributing to early proximal renal dysfunction in FBS. Six out of our 10 patients had impaired glucose tolerance. In conclusion the early occurrence of renal tubular acidosis, especially under the age of one years with elevated levels of HbA1C is a key point of thinking FBS in the differential diagnosis.

Introduction Isovaleric acidemia (IVA) is a rare autosomal recessively inherited metabolic disorder caused by deficiency of isovaleryl-Co A dehydrogenase. Clinical signs are refusal of feeding, vomiting, lethargy, convulsions, metabolic acidosis, hyperglycemia/hypoglicemia, and foot odor in neonatal period. Munchausen by proxy syndrome is a complex form of childhood abuse that can be sometimes severe and fatal. A caregiver intentionally creates some symptoms mimicking an organic disease or changing the laboratory samples that causes damages in child health. Case The patient who was diagnosed as IVA at 2-months of age had no other metabolic attacks until the age of seven. After that, he was hospitalized in every 3–4 months with severe dehydration and renal failure and hemodiafiltration was performed. The levels of creatinin and potassium are incompatible with life and there were any sustaining clinical or electrocardiographical signs. His 2 year-old sister and 6 month-old brother who had also IVA were also hospitalized with recurrent encephalopathic status. As the family had a history of a child death without a known cause and the siblings had frequent hospitalizations in different medical centers and cities without a triggering factor, a more detailed anamnesis was obtained from the mother. Suprisingly this new history put forward the usage of antipsychotic/anatidepressive drugs in all siblings which lead to recurrent encephalopathies. However, renal insufficiency could not be explained until the mother’s mixing of her urine to the blood samples of the child was observed in the clinic. Conclusion Munchausen by proxy syndrome is a severe form of child abuse that can even result in death of the child if the diagnosis is not established in time. Although our patients had a known inherited metabolic disease with a defined mutation, the mother did not tell anything about this or sometimes told lies on the admissions to different medical centers. These confusing anamnesis easily lead the other physicians to the diagnosis of more common diseases like acute renal insufficiency, encephalities, and diabetes. Then, lots of unnecessary procedures was performed until the munchausen by proxy syndrome was thought. We present this case to emphasize thinking Munchausen by proxy syndrome with recurrent unexplained signs and symptoms even in the presence of a known disease in order to prevent undesirable results.

Introduction Phenylketonuria (PKU) is the most common and autosomal recessively inherited metabolic disease due to the deficiency of phenylalanine hydroxylase (PAH). Elevated levels of phenylalanine are not only toxic for the children but also teratogenic for the fetus. Clinical findings of maternal phenylketonuria (MPKU) are intrauterine growth retardation, microcephaly, significant developmental delay, congenital cardiac anomalies, and some other structural defects. Poorly diet control and high levels of blood phenylalanine causes to this severe but preventable clinical syndrome. Case report A seven-day-old girl admitted to the pediatric metabolism clinic with a suspicion of PKU after newborn screening program. She was born at 40 weeks of gestation with a 2300 gr birth weight and hospitalized for 2 days. Her parents were first degree cousins and the family history was unremarkable for an inherited metabolic disease, however the mother had two miscarriages. Physical examination revealed microcephaly, mild facial dysmorphism, and cardiac murmur in addition to intrauterine growth retardation. Her blood phenylalanine level was 1140 µmol/dL and she was diagnosed as moderate phenylketonuria. As a ventricular septal defect was detected with echocardiography and the mother was born before the national newborn screening program was available, the mother’s blood Phe concentration was measured. Surprisingly her blood Phe level was 1614 µmol/dL. The mother was a 25 years old woman be able to graduate from primary school and. complained about only concentration problems and forgetfulness. She had also blond hair and blue eyes on physical examination. Conclusion Maternal phenylketonuria is a preventable public health problem which causes undesirable results like mental-motor retardation and cardiac defects. Although maternal phenylketonuria is not completely coped with, after newborn screening program the incidence is decreased. A strict Phe restricted diet beginning before the pregnancy together with frequent controls of blood Phe levels are essential for management. Here, we report this case, as she was diagnosed both phenylketonuria and maternal phenylketonuria and in order to emphasize thinking MPKU in the presence of microcephaly, developmental delay, and cardiac defects. Maternal phenylketonuria, newborn screening program, developmental delay.

PubMedID: 29159724 Ethylmalonic 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.

Amac: Ure dongusu birincil olarak karacigerde amonyaktan urenin uretildigi bir metabolik yolaktir. Ure dongusu enzim eksiklikleri bu metabolik yolun dogustan gelen hatalaridir. Karbamoilfosfat sentaz (CPS-1), ornitin transkarbamilaz (OTC), argininosuksinat sentaz (ASS), argininosuksinat liyaz (ASL), arginaz (ARG) ve N-asetilglutamat sentaz (NAGS) eksiklikleri nedeniyle ure dongusunde azot atiliminin azalmasi hiperamonemiye neden olur. Sik gorulen belirti ve bulgular bulanti-kusma, istahsizlik, hiperamonemi, yagli karaciger, hepatomegali, karaciger yetmezligi, konvulziyonlar, uykuya meyil, koma ve zihinsel geriliktir. Gerec ve Yontemler: Calismada, Turkiye’nin guneyindeki ure dongusu enzim eksikligi tanisi alan 20 hastanin klinik verileri, mutasyon analizleri ve prognozlari retrospektif olarak degerlendirildi. Bulgular: Calismaya 17 aileden 20 hasta (12 kiz / 8 erkek) alindi. Baslica basvuru yakinmalari; gelisim basamaklarinda gerilik, diger norolojik bulgular, beslenme zorlugu, kusma, takipne, ailede nedeni bilinmeyen cocuk olum oykusu olmasi ve supheli yenidogan taramasi sonuclariydi. Ebeveynlerin cogu (15/17) akrabaydi. Aile oykusu orani 8/17 idi. Ortalama semptom yasi uc gun (0 gun-3 yil)’di. Yenidogan doneminde basvuran 12 hastada hiperamonemi vardi. Dokuz hasta-sitrullinemi tip 1, alti hasta arginaz eksikligi, iki hasta CPS-1 eksikligi, bir hasta OTC eksikligi, bir hasta ASL eksikligi ve bir hasta NAGS eksikligi tanisi aldi. Hastalarin genetik analizleri 14 farkli mutasyondan sekiz yeni mutasyon saptandi. Akut metabolik kriz sirasinda bes hasta oldu. Sonuc: Literaturde OTC eksikligi en sik gorulen form olmasina ragmen, ure dongusu enzim eksiklikleri arasinda literaturde bildirilene gore daha yuksek oranda sitrullinemi saptadik. Otozomal resesif kalitsal hastaliklarin daha fazla oranda gorulmesine katkida bulunan akraba evliligi sikliginin yuksek olmasina ragmen, hastalarimizda genetik heterojenite gozlenmistir. Ayrica bu degerlendirme ile ure dongusu enzim eksikliklerinin mutasyon spektrumuna sekiz yeni mutasyon daha eklenilmistir.

Background: Congenital hypothyroidism (CH) is a common cause of mental retardation; it has a worldwide incidence ranging from 1:3000 to 1:4500 live births. Predictably, an increase in the reported incidence of primary CH occurs when the cut-off levels of thyroid-stimulating hormone are lowered. We aimed to evaluate the results of a congenital hypothyroidism screening program and current status in this study. Methods: Analysis results of 1300 infants who were referred to the endocrinology polyclinic because of suspected CH within the scope of the Ministry of Health National Neonatal Screening Program were retrospectively evaluated. Results: The diagnosis of CH and initiation of treatment were both done in 223 (18.5%) and 10 (0.8%) infants as a result of the initial evaluation and follow-up, respectively. The mean capillary and venous thyroid-stimulating hormone (TSH) levels of 223 patients were 40.78 (5.5–100) μIU/mL and 67.26 (10.7–100) μIU/mL, respectively. These patients’ mean heel prick time was 8.65 (0–30, median: 7) days. The mean age of the 223 infants whose treatment was initiated as a result of the initial evaluation was 19.87 (4–51, median: 20) days, and the mean age of the infants whose treatment was started at follow-up was 43.71 (29–65) days. The duration between heel prick time and venous TSH time was 11.10 (2–28, median: 11) days and was longer than planned (3–5 days). Conclusions: Although the duration for the diagnosis and initiation of CH treatment were markedly reduced with the implementation of the screening program in Turkey compared to those before the implementation of the screening program, we have not yet achieved the ideal time (≤14 days).

We're Organizing Research for Lysosomal Diseases (WORLD) Symposium -- FEB 05-09, 2018 -- San Diego, CA WOS: 000424963800259 …

WOS: 000437396300022, PubMed ID: 29656334, Gaucher 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.

Tyrosinemia type I is a metabolic disease of tyrosine metabolism due to the deficiency of fumarylacetoacetate hydrolase (FAH) enzyme which is inherited in an autosomal recessive manner and is characterized by severe hepatocellular degeneration (1). This disorder was first described by Sakai and Kitogawa in 1957 (2). The incidence is about 1/100000 (3). Clinical manifestations of untreated cases are hepatic failure, cirrhosis, hepatocellular carcinoma, renal fanconi syndrome, and neurologic crisis. After introducing Nitisinone (2-(2-nitro-4-trifluoro-methylbenzyol)-1.3 cyclohexanedione) (NTBC) (Orfadin; Sobi, Stockholm, Sweden) to the treatment and with the restriction of tyrosine and phenylalanine in the diet, the prognosis improves and a limited number of complications have been reported. This treatment can prevent neurologic crises, acute hepatic failure, and renal tubular acidosis (4). Neurologic crisis is a rare but fatal complication of tyrosinemia type I characterized by anorexia, vomiting, and sometimes self-mutilation, with hyponatremia in the initial phase, and continuing with paresthesia, autonomic symptoms and possible progression to paralysis of the extremities and diaphragm and death. Acute pancreatitis is transient inflammation of the pancreas. The diagnosis is made with two of the three criteria listed below: clinical symptoms of severe abdominal pain, vomiting, elevation of serum and urine amylase or lipase levels three times from the upper limit and radiological evidence of pancreatitis by ultrasonography or tomography. The etiology of pancreatitis in children is quite diverse: anatomical anomalies, drugs, trauma, biliary problems, genetic causes, hyperlipidemia, organic acidemia, and postsurgical problems of the gastrointestinal system. When it is possible to rule out all causes, an idiopathic pancreatitis diagnosis can be made (5). In the literature, tyrosinemia type I with pancreatitis was only reported in one case (6). Here, we report a case of tyrosinemia type I and pancreatitis, as pancreatitis could be a rare underestimated complication of tyrosinemia type I and our patient has a confusing clinical manifestation, mimicking neurologic crisis.

PubMedID: 27188289 Tyrosinemia type I is an autosomal recessively inherited metabolic disease of tyrosine metabolism due to the deficiency of fumarylacetoacetate hydrolase. Clinical manifestations include hepatic failure, cirrhosis, hepatocellular carcinoma, renal fanconi syndrome, and neurologic crisis. With the introduction of 2-(2-nitro-4-trifluoro-methylbenzyol)-1,3 cyclohexanedione treatment the prognosis improved with reduced rate of complications. “Neurologic crisis” of tyrosinemia type I is a rare complication seen after discontinuation of treatment characterized with anorexia, vomiting, and hyponatremia in the initial phase continuing with paresthesia and paralysis of the extremities and the diaphragm. Here, we report a tyrosinemia type I patient who admitted to the hospital with nonspecific symptoms such as vomiting, anorexia, weakness, and restlessness only after one month discontinuation of nitisone and diagnosed as neurological crisis. © 2016, Springer Science+Business Media New York.

PubMedID: 24838951 Nonketotic hyperglycinemia (OMIM no. 605899) is an autosomal recessively inherited glycine encephalopathy, caused by a deficiency in the mitochondrial glycine cleavage system. Here we report 2 neonates who were admitted to the hospital with complaints of respiratory failure and myoclonic seizures with an elevated cerebrospinal fluid/plasma glycine ratio and diagnosed as nonketotic hyperglycinemia. We report these cases as 2 novel homozygous mutations; a missense mutation c.593A>T (p.D198 V) in the glycine decarboxylase gene and a splicing mutation c.339G>A (Q113Q) in the aminomethyltransferase gene were detected. We would like to emphasize the genetic difference of our region in inherited metabolic diseases once again. © The Author(s) 2014.

Background:Phenylketonuria (PKU) often requires a lifelong phenylalanine (Phe)-restricted diet. Introduction of 6R-tetrahydrobiopterin (BH4) has made a huge difference in the diets of patients with PKU. BH4 is the co-factor of the enzyme phenylalanine hydroxylase (PAH) and improves PAH activity and, thus, Phe tolerance in the diet. A limited number of published studies suggest a pharmacodynamic profile of BH4 more suitable to be administered in divided daily doses.Methods:After a 72-h BH4 loading test, sapropterin was initiated in 50 responsive patients. This case-control study was conducted by administering the same daily dose of sapropterin in group 1 (n=24) as a customary single dose or in two divided doses in group 2 (n=26) over 1 year.Results:Mean daily consumption of Phe increased significantly after the first year of BH4 treatment in group 2 compared to group 1 (pConclusions:When given in two divided daily doses, BH4 was more efficacious than a single daily dose in increasing daily Phe consumption, Phe tolerance and the ability to transition to a Phe-unrestricted diet at the end of the first year of treatment.

We're Organizing Research for Lysosomal Diseases (WORLD) Symposium -- FEB 05-09, 2018 -- San Diego, CA WOS: 000424963800258 …

Kör D, Şeker-Yılmaz B, Bulut FD, Kılavuz S, Öktem M, Ceylaner S, Yıldızdaş D, Önenli-Mungan N. Clinical features of 27 Turkish Propionic acidemia patients with 12 novel mutations. Turk J Pediatr 2019; 61: 330-336. 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.

McArdle hastaligi, cizgili kasta glikojen fosforilaz enziminin eksikligi sonucu gelisen, otozomal resesif kalitim gosteren bir hastalik olarak tanimlanmaktadir. Hastalar genellikle cabuk yorulma ve egzersiz sonrasi gucsuzluk ile birlikte, kas kramplari, agri ve azalmis egzersiz toleransindan yakinirlar. Uzun sureli efor sonrasi kontraktur, rabdomiyoliz ve miyoglobinuri olusabilir. Merkezi sinir sistemi belirtileri McArdle hastaliginda nadiren bildirilmistir. Burada, epilepsi ve McArdle hastaligi olan 13 yasindaki bir cocuk sunulmustur

önenli-Mungan N, KörD, Karabay-Bayazıt A, Cengiz N, YavuzS, NoyanA, CeylanerG, Şeker-Yılmaz B, TopaloğluAK, YükselB, AnaratA. Genotypic and phenotypic features of the cystinosis patients from the South Eastern part of Turkey. Turk J Pediatr 2016; 58: 362-370.We have conducted this study for the purposes of demonstrating the spectrum of mutations and of identifying their effects on the phenotype, with a particular focus on the clinical course, prognosis and response to treatment. A total of 25 patients from 20 families, who have been treated and followed up after being diagnosed with cystinosis. Nine patients were identified with mutations of homozygous c.451A>G, 7 patients with homozygous c.681G>A, 6 patients with homozygous c.834_842del, 2 patients with homozygous c.18_21delGACT and 1 patient with compound heterozygous for c.451A>G/ c.1015G>A. The c.834_842del mutation identified in six patients from four families has not been previously identified.Progression to renal failure occurred earlier in the patients identified with the new mutation, despite treatment. Larger patient series are required to demonstrate the genotypic properties of the patients with cystinosis and their relationship with the clinical course. önenli-Mungan N, KörD, Karabay-Bayazıt A, Cengiz N, YavuzS, NoyanA, CeylanerG, Şeker-Yılmaz B, TopaloğluAK, YükselB, AnaratA. Genotypic and phenotypic features of the cystinosis patients from the South Eastern part of Turkey. Turk J Pediatr 2016; 58: 362-370.We have conducted this study for the purposes of demonstrating the spectrum of mutations and of identifying their effects on the phenotype, with a particular focus on the clinical course, prognosis and response to treatment. A total of 25 patients from 20 families, who have been treated and followed up after being diagnosed with cystinosis. Nine patients were identified with mutations of homozygous c.451A>G, 7 patients with homozygous c.681G>A, 6 patients with homozygous c.834_842del, 2 patients with homozygous c.18_21delGACT and 1 patient with compound heterozygous for c.451A>G/ c.1015G>A. The c.834_842del mutation identified in six patients from four families has not been previously identified.Progression to renal failure occurred earlier in the patients identified with the new mutation, despite treatment. Larger patient series are required to demonstrate the genotypic properties of the patients with cystinosis and their relationship with the clinical course.

Mutations in the AGK gene are known to cause Sengers Syndrome, a rare recessive disorder characterized by congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, exercise intolerance and lactic acidosis with normal mental development. Since the first report in 1975 by Sengers et al. about 50 individuals have been described as having this syndrome. Here we report two novel mutations in the AGK gene in two patients with neonatal Sengers syndrome.

PubMedID: 26444347 Brown-Vialetto-Van Laere syndrome (BVVLS) is a rare and severe neurometabolic disease. We present two siblings with BVVLS with a novel homozygous mutation in SLC52A3 (formerly C20orf54) gene. The first sibling was admitted with respiratory insufficiency and required mechanical ventilation. After administration of a high dose of riboflavin, all his clinical symptoms were resolved, which also strongly suggested the diagnosis of BVVLS. The second sibling was also found to have the same genetic mutation as her brother. Although she was symptom-free, riboflavin was initiated empirically. On follow-up, she developed no neurologic or metabolic problems with entirely normal growth and development. BVVLS should be considered in the differential diagnosis of unexplained neurologic symptoms such as polyneuropathy and respiratory insufficiency, as BVVLS and multiple acyl-CoA dehydrogenation defect have broadly overlapping symptoms. Furthermore, our cases once again suggest that with proper diagnosis and early high-dose riboflavin treatment, complete reversal of neurologic deficits in BVVLS is possible. © 2016 by De Gruyter.

Although propionic acidemia (PA) is a devastating inherited metabolic disease, with early diagnosis and advanced treatment strategies prognosis gets better and girls can survive to child-bearing ages. We share the detailed follow-up data of the pregnancy, successful labor with cesarean section and a healthy baby of a Turkish patient with PA.

Aim The aim of this study was to determine the prevalence and correlates of restless legs syndrome (RLS) in adolescents. Method A sleep questionnaire aimed at identifying ‘definite’ RLS criteria (also including the Strengths and Difficulties Questionnaire and the Epworth Sleepiness Scale) was completed by 3304 high school adolescents aged 15 to 18 years (49% male; 51% female) in Gaziantep, Turkey. The diagnosis of RLS was confirmed by face-to-face or phone interviewing. The χ2 or Student’s t-test and logistic regression tests were used for statistical evaluation. Results ‘Definite’ RLS was diagnosed in 3.6% of participants. RLS symptoms were reported to occur on more than one occasion per week (frequent RLS) in 2% of participants and to make it to difficult to fall asleep or stay asleep (RLS with sleeping difficulty) in 1.7%. The prevalence of the combination of frequent symptoms and sleeping difficulty was 0.8%. Logistic regression analysis revealed that RLS was independently associated with nocturnal bed-wetting (4.2% vs 0.8%; p=0.004), sleeping difficulty (47% vs 32%; p=0.011), Epworth Sleepiness Scale score (4.9 vs 3.9; p=0.036), hyperactivity/inattention (25% vs 14%; p=0.049), awakening with discomfort in the legs (51% vs 30%; p