Ghrelin Levels in Children with Constitutional Delay of Growth and Puberty

Objective: In this study, we aimed to show the role of ghrelin in growth delay in children with constitutional delay of growth and puberty (CDGP)

False Positive Diagnosis of Lysosomal Storage Disease Based on Dried Blood Spot Sample; Leucocyte Number of a Challenging Factor

Aim:Recently dried blood spot (DBS) samples have been recommended as a screening test for Lysosomal Storage diseases. Although DBS samples have many advantages including non-invasiveness, cost and transportation, usage of these samples is limited by its high false positive rate. We aimed to investigate any possible effect of the leucocyte number on enzyme activity in dried blood samples in a retrospective study.Materials and Methods:Data was collected from subjects (n=263) for whom hematological parameters were available in the database of Ege University Hospital. The lysosomal enzyme activity results (alpha glycosidase, glycocerebrosidase, alpha galactosidase, sphingomyelinase and galactocerebrosidase) were re-evaluated with regard to the leucocyte number. Enzyme activities were measured using fluorometric and liquid chromatography-tandem mass spectrometry methods.Results:All enzyme activities closely correlated with the total number of leucocyte, since leucocytes are the main source of lysosomal enzymes. Glycocerebrosidase and galactocerebrosidase presented a positive correlation with the number of neutrophils and sphingomyelinase showed a positive correlation with the number of lymphocytes. When we recalculated the lysosomal enzyme activities with regard to the leucocyte number, the false positive rates for glycocerebrosidase, sphingomyelinase and alpha galactosidase decreased from 20%, 10.5% and 10.8% to 4.5%, 4.4% and 4.2%, respectively.Conclusions:Our data indicated that the enzyme activity in dried blood samples including low leucocyte number might be found lower than reference intervals resulting in false positive diagnosis. We concluded that the calculation of enzyme activity with regard to the number of leucocytes might produce more reliable results and might be helpful in decreasing the false positive rate

Case Report A Patient with MSUD: Acute Management with Sodium Phenylacetate/Sodium Benzoate and Sodium Phenylbutyrate

In treatment of metabolic imbalances caused by maple syrup urine disease (MSUD), peritoneal dialysis, and hemofiltration, pharmacological treatments for elimination of toxic metabolites can be used in addition to basic dietary modifications. Therapy with sodium phenylacetate/benzoate or sodium phenylbutyrate (NaPB) in urea-cycle disorder cases has been associated with a reduction in branched-chain amino acid (BCAA) concentrations when the patients are on adequate dietary protein intake. Moreover, NaPB in treatment of MSUD patients is also associated with reduction of BCAA levels in a limited number of cases. However, there are not enough studies in the literature about application and efficacy of this treatment. Our case report sets an example of an alternative treatment's efficacy when extracorporeal procedures are not available due to technical difficulties during attack period of the disease

Clinical Features of 29 Patients with Hereditary Tyrosinemia I in Western Turkey

Aim:The aim of this study was to investigate the long-term outcome of hereditary tyrosinemia Type I (HTI) patients treated with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) to increase knowledge about the clinical outcome in these patients. We want to mention that the patients with HTI have heterogeneous clinic. Early diagnosis and early treatment important to prevent the complications.Materials and Methods:Aretrospective study was carried out with twenty nine patients with HTI and who had been followed up by Ege University Faculty of Medicine, Department of Pediatric Metabolic Diseases and Nutrition Unit between December 1996 and September 2017.Results:Eight patients were acute form, thirteen were subacute and eight patients were chronic form. Mean age onset of clinical symptoms was 3.7±1.6, 9±1.6 and 41±27 months in acute, subacute and chronic HTI patients, respectively. The mean interval from the first symptom the diagnosis was 12.2 months. Mean of follow-up was 82.2 months (minimum: 1 month-maximum: 203 months). Five patients of HTI diagnosed with hepatocellular carcinoma and neurogenic crises were detected in four patients.Conclusion:NTBC treatment is effective and improves the prognosis of HTI. But early diagnosis and treatment leads to much better outcome. Adherence to the diet and treatment and follow-up schedule of the patients are vital

Clinical, Biochemical and Molecular Characteristics of Fifteen Patients with Mucopolysaccharidosis Type II in Western Turkey

Aim:Mucopolysaccharidosis Type II (MPS II, Hunter syndrome, OMIM 309900) is a rare X-linked lysosomal storage disease due to a deficiency of the iduronate-2-sulfatase (IDS) enzyme, which is one of the degradative enzymes of mucopolysaccharides. The purpose of this study is to present the clinical, biochemical and molecular characteristics of fifteen patients with MPS II in western Turkey.Materials and Methods:A retrospective study was carried out on fifteen patients with MPS II who were followed up by Ege University Faculty of Medicine, Unit of Pediatric Metabolic Diseases and Nutrition between October 2004 and September 2017.Results:The age range of the patients enrolled in the study was between 11 months and 318 months at the time of diagnosis. The most common symptom was coarse face. On physical examination, all of the patients presented with coarse face, macrocephaly and organomegaly. Except for one patient, all other were severe phenotype. IDS activity was significantly decreased in all patients in whom enzyme analysis was performed. In this study, one novel mutation was described.Conclusion:This is the first study on the clinical and molecular characterization of Turkish MPS II patients. The majority of the patients had neurologic involvement with different degrees of severity. The molecular analysis revealed one novel mutation

Tyrosinemia Type I and Reversible Neurogenic Crisis After a One-Month Interruption of Nitisinone

Hereditary tyrosinemia Type I (HTI) is an autosomal recessive disorder due to a deficiency of the enzyme fumarylacetoacetate hydrolase. The liver is the primary organ that is affected and comorbidities with renal and neurologic systems and hepatocellular carcinoma can be seen as a long-term complication. An effective treatment has been available with 2-[2-nitro-4-trifluoromethylbenzoyl]-1,3-cyclohexanedione (NTBC) since 1992. Neurogenic crises do not take place in HTI patients who are treated with NTBC. Here, we report on a seven-year-old boy who underwent a severe neurological crisis including anorexia, vomiting, weakness, hyponatremia, paresthesia and paralysis of the extremities, seizure and arterial hypertension after an interruption of NTBC treatment. With the re-introduction of NTBC, the patient gradually reacquired normal neurological functions, normal blood pressure and recovered completely

COMPARISON OF APOLIPOPROTEIN E GENE POLYMORPHISM AND PLASMA LIPID AMOUNTS IN OBESE AND DISLIPIDEMIC TURKISH CHILDREN

Amaç: Apolipoprotein E gen polimorfizmi ile lipid metabolizması arasındaki ilişkipopulasyon çalışmalarında ortaya konulmuştur. Obez olan çocuklarda apolipoproteinE gen polimorfizmi ile plazma lipid düzeyleri arasındaki ilişki ve obezite ilebirlikte olan dislipidemilerde apolipoprotein E gen polimorfizmi araştırılmıştır.Yöntemler: İnsülin bağımlı diyabeti, karaciğer ve böbrek yetmezliği bulunmayan,plazma lipid düzeyini etkileyecek ilaç kullanmayan, primer obezitesi bulunan 57 çocukve normal kilolu 18 çocuk olmak üzere toplam 75 çocuğun plazma lipid düzeylerinebakılmış ve apolipoprotein E (Apo E) gen polimorfizmi polimeraz zincir reaksiyonu ileanaliz edilmiştir.Bulgular: Obez çocuklarda Apo AI düzeyleri yüksek saptanmıştır. Obez ve obezolmayan grupta E2/E3 dağılımı sırasıyla %10,5, %27,8; E3/E3 dağılımı sırasıyla %80,7,%61; E3/E4 dağılımı sırasıyla %7, %5,6 olarak bulunmuştur. Obez olan grupta E4/E4fenotipi, obez olmayan grupta E2/E4 fenotipi görülmemiştir. Obez olan grupta E2/E4dağılımı %1,8, obez olmayan grupta E4/E4 fenotip dağılımı %5,6 bulunmuştur. Allelsıklıkları obez ve obez olmayan grupta sırasıyla epsilon 2 (ε2) alleli için %6,1, %14;epsilon3 (ε3) alleli için %89,5, %78; epsilon 4 (ε4) alleli için %4,4, %8 olarak benzerbulunmuştur. Bütün gruplarda en sık allelin ε3 olduğu görülmüştür.Sonuç: Apo E allel ve fenotip dağılımının obez ve sağlıklı çocuklarda benzer olduğugözlenmiştir. Obez çocuklarda total kolesterol, Apo B, Apo AI ortalama düzeyi, obezolmayan çocuklara göre daha yüksek bulunmuş, trigliserid düzeyleri obez olan gruptaobez olmayan gruba göre belirgin yükseklik göstermiştir. Objective: The relationship between Apolipoprotein E (Apo E) gene polymorphismand lipid metabolism was presented by the population studies. The aim of this studywas to search the relationship between Apo E gene polymorphism and plasma lipidlevels in obese children and to search Apo E gene polymorphism in dislipidemiascoexisting with obesity. Methods: Seventy five children (57 were primary obese, 18 were normal weight) wereanalysed by polymerase chain reaction for Apo E gene polymorphism and plasmatriglyceride, HDL, LDL and Apo B amounts were evaluated. Excluding criterias for thestudy group are insulin dependent diabetes mellitus, hepatic and renal failure andmedication because of they might affect the lipid concentration in plasma.Results: The Apo AI levels were significantly elevated in obese children. HDL, LDLand Apo B levels were nearly at the same levels while triglycerides levels were muchhigher in obese group than non-obese group, but the difference was not foundstatistically significant. In obese and non-obese group the E2/E3 distribution was10.5% and 27.8%; E3/E3 was 80.7% and 61% and E3/E4 was 7% and 5.6% respectively.The E4/E4 phenotype was not determined in obese group while the E2/E4 phenotypewas not seen in non-obese group. E2/E4 distribution was 1.8% in obese children andE4/E4 distribution was 5,6% in non-obese children . Allele frequencies in obese andnon-obese children for epsilon 2 (ε2) were found as 6.1% and 14%; for epsilon 3 (ε3)89.5% and 78% and for epsilon 4 (ε4) 48% and 4% respectively. There was no significantdifference between the groups according to allele frequency (p>0.05). The ε3 was foundthe most frequent allele in all the groups.Conclusion: Apo E allele and phenotype distribution were found similar in obese andnon-obese children. The Apo AI levels were significantly elevated in obese children

Nephrotic syndrome in a patient with Glycogen Storage Disease Type IXb.

Introduction: Glycogen storage disorder (GSD) IXb is characterized by liver and muscle involvement. We present a GSD IXb patient with an incidental union of nephrotic syndrome. Case Report: A 4 year-old-patient was diagnosed with GSD IXb at 13 months of age with mildly elevated transaminases and hepatomegaly. During the follow-up period, there was no hypoglycemia. Development and growth were normal. In the last month, the onset of generalized edema was reported. Urinalysis showed a high protein level. He had low serum albumin, high serum triglycerides cholesterol. Complement levels were normal. The patient was diagnosed as minimal change disease with a renal biopsy. He was treated with oral prednisone. Discussion: Minimal Change Disease is the most common cause of idiopathic nephrotic syndrome cases in children and the first step for therapy is the usage of corticosteroids. This is the first report of nephrotic syndrome associated with GSD IXb disease

Clinical, Neuroimaging, and Genetic Features of the Patients with L-2-Hydroxyglutaric Aciduria

Aim:L-2-hydroxyglutaric aciduria (L2HGA) is a rare autosomal recessive encephalopathy caused by mutations in the L-2-hydroxyglutarate dehydrogenase gene.Materials and Methods:Here we discuss the clinical and molecular characteristics in patients with L2HGA.Results:There were eight patients with L2HGA. Their median age was 16 (9.5-37) years. Five of them were female and three of them were male. The main symptoms of the patients were psychomotor retardation (8/8), cerebellar ataxia (5/8), extrapyramidal symptoms (7/8) and seizures (4/8). All patients had behavioral problems. Elevated urinary L-2-hydroxy (L-2-OH) glutaric acid was detected and the median level of urine L-2-OH glutaric acid at diagnosis was 146 (60-1460 nmol/mol creat). Characteristic magnetic resonance imaging findings including subcortical cerebral white matter abnormalities with T2 hyperintensities of the dentate nucleus, globus pallidus and putamen were detected. Two patients had homozygous R335X, two patients had homozygous R282Q, two patients had homozygous R302L and one patient had compound heterozygous P302L/A64T mutation in L-2-hydroxyglutarate dehydrogenase (L2HGDH) gene.Conclusion:Because of the slow progression of the disease, the diagnosis of the patients is usually belated. L2HGA must be considered in the differential diagnosis based on clinical findings and specific findings in cranial magnetic resonance imaging. In our study, one of our patients has a novel mutation

Glutaric Aciduria Type I Diagnosis Case with Normal Glutaryl Carnitine and Urine Organic Acid Analysis

Glutaric aciduria Type I (GA-I) is a rare inherited metabolic disease, deficiency of glutaryl-CoA dehydrogenase results in accumulation of the putatively neurotoxic metabolites glutaric and 3-hydroxyglutaric acid (GA, 3-OH-GA) in body tissues, particularly within the brain. Here we presented a 3-year-old girl with hypotonia and dystonia diagnosed with GA-I although the repeated analysis of the carnitine profile and organic acid analyses were normal. The patient has motor, mental retardation, hypotonia. Her weight standard deviation score (SDS) was -1.86 SDS, height SDS was -0.55 SDS, head circumference SDS was -1.01. The physical examination was normal except severe hypotonia. Spot blood carnitine profile, blood amino acid, urine organic acid, lactic acid and pyruvic acid were normal in repeated analysis. Dystonia and spastic tetraparesis developed on her follow-up. Cranial magnetic resonance imaging revealed bilateral cortical atrophy and bilateral striatal and caudate nucleus T2 flair hyperintensities. In GCDH gene analysis p.Y123C (c.368A>G)/p.L340F (c.368A>G) mutation was found. There was no history of encephalopathy. The patient treated with levodopa and trihexyphenidyl and lysine-restricted diet. In the presence of bilateral striatal involvement and cortical atrophy and dystonia, GA-I should be kept in mind. Blood carnitine profile and urine organic acid analyses may not be consistent. It is important to evaluate the cases for genetic investigation