Evaluation of Lysosphingolipid Analysis for the Diagnosis of Lysosomal Storage Disease.

Lysosomal storage disorders (LSD) are a group of inherited inborn metabolism errors that are characterized by a deficiency in the lysosomal enzyme. In patients with suspected lipid storage disorders, confirmation of the diagnosis relies predominantly on the measurement of specific enzymatic activities and molecular genetic studies. New approaches to the measurement of lysosphingolipids have been developed that may serve as a rapid first-tier screening tests for the evaluation of lysosomal storage disorders.

Pterin Profiling in Serum, Dried Blood Spot, and Urine Samples Using LC-MS/MS in Patients with Inherited Hyperphenylalaninemia.

Background: Hyperphenylalaninemia (HPA) is defined as blood phenylalanine (Phe) levels exceeding the normal values (>120 μmol/L or >2 mg/dL) and is caused by a deficiency in the enzyme phenylalanine hydroxylase (PAH). The widespread screening of Phe levels in newborn screening programs has led to a very high number of patients with HPA.

Methods: The samples were collected at various ages, not at the point of diagnosis.

Endocrinological and metabolic profile of Gaucher disease patients treated with enzyme replacement therapy.

Objectives: Gaucher disease (GD) is a lysosomal storage disease caused by glucocerebrosidase (GCase) enzyme deficiency. Gaucher cells transformed from the macrophages by progressive sphingolipid accumulation and infiltrate bone marrow, spleen, liver, and other organs. The accumulation of substrate causes inflammation, compromised cellular homeostasis, and disturbed autophagy.

Is lysosomal acid lipase activity associated with the presence and severity of coronary artery disease?

Background: Lipid metabolism is considerably complex and there can be many critical steps in atherogenesis. The association between lysosomal acid lipase (LAL) activity and coronary artery disease (CAD) has not been elucidated in detail. We aimed to evaluate the association between LAL activity with the presence and severity of CAD in patients who are seen in daily clinical practice.

Diagnostic value of plasma lysosphingolipids levels in a Niemann-Pick disease type C patient with transient neonatal cholestasis.

Objectives: Niemann-Pick disease type C (NPC) is a lysosomal storage disease due to impaired intracellular lipid trafficking caused by biallelic pathogenic variants in or genes. NPC is classified according to the age of onset of neurological manifestations. Cholestatic liver disease can be transient or lead to liver failure.

Expected or unexpected clinical findings in liver glycogen storage disease type IX: distinct clinical and molecular variability.

Objectives: To reveal the different clinical presentations of liver glycogen storage disease type IX (GSD IX), which is a clinically and genetically heterogeneous type of glycogenosis.

Methods: The data from the electronic hospital records of 25 patients diagnosed with liver GSD IX was reviewed. Symptoms, clinical findings, and laboratory and molecular analysis were assessed.

Clinical and event-based outcomes of patients with mucopolysaccharidosis VI receiving enzyme replacement therapy in Turkey: a case series.

Background: The objective of this study was to describe clinical manifestations and events of patients with mucopolysaccharidosis (MPS) VI in Turkey who are treated with galsulfase enzyme replacement therapy (ERT). Clinical data of 14 children with MPS VI who were followed up at the Department of Pediatrics of the Gazi University Faculty of Medicine in Ankara, Turkey were retrospectively collected from the patients' medical records. Patients were selected based on availability of a pre-ERT baseline and follow-up clinical data for a similar period of time (1.

Congenital defects of glycosylation: Novel presentations with mainly neurological involvement and variable dysmorphic features.

The pathophysiology of congenital defects of glycosylation (CDG) is complex and the diagnosis has been a challenge because of the overlapping clinical signs and symptoms as well as a large number of disorders. Isoelectric focusing of transferrin has been used as a screening method but has limitations. Individual enzyme or molecular genetic tests have been difficult to perform.

The first case with FBXL4 mutation successfully treated with a parenteral ketogenic diet for lactic acidosis.

Background: The ketogenic diet (KD) is a low-carbohydrate, high-fat diet that has been used as an effective nonpharmacological treatment in many neurological and metabolic disorders for a long time. The effectiveness of the KD is revealed in mitochondrial disorders, mainly in pyruvate dehydrogenase deficiency.

Case Report: A 4-year-old girl who was diagnosed with an F-box and leucine-rich repeat protein 4 (FBXL4) gene mutation was hospitalized with sepsis.

Two patients from Turkey with a novel variant in the gene and review of the literature.

Objectives: GM2 gangliosidosis is a rare form of inborn errors of metabolism including Tay-Sachs disease, Sandhoff disease, and GM2 activator deficiency. GM2 activator protein deficiency is an ultra-rare form of GM2 gangliosidosis. To date, 16 cases of GM2 activator protein deficiency have been reported in the literature, and among them, 11 cases were the infantile form of the disease.

Autism: Screening of inborn errors of metabolism and unexpected results.

In this study, the aim was to examine patients with inborn errors of metabolism (IEM) who presented with only autism, without any other findings, to suggest any other neurological and genetic disorders. To investigate IEM, data of the hospital records of 247 patients who were referred from pediatric psychiatric to pediatric metabolism outpatient clinics due to further evaluation of autism spectrum disorders (ASD) were examined. Among them, 237 patients were evaluated for IEM leading to ASDs.

Hypophosphatasia: is it an underdiagnosed disease even by expert physicians?

Introduction: Hypophosphatasia (HPP) is caused by mutations in the ALPL that encodes the tissue-nonspecific isoenzyme of alkaline phosphatase (ALP). Clinical manifestations range from extreme life-threatening lethal forms to no signs or symptoms at all.

Materials And Methods: Consecutive 30,000 outpatients and inpatients with ALP data were screened retrospectively, out of which 1000 patients were found to have low levels of ALP more than once.

A rare urea cycle disorder in a neonate: N-acetylglutamate synthetase deficiency.

Urea cycle disorders (UCD), are genetically inherited diseases that may have a poor outcome due to to profound hyperammonemia. We report the case of a baby girl diagnosed as N-acetylglutamate synthase (NAGS) deficiency. The patient was evaluated due to diminished sucking and hypotonicity.

Beneficial Effects of Modified Atkins Diet in Glycogen Storage Disease Type IIIa.

Introduction: Glycogen storage disease Type III (GSD III) is an autosomal recessive disease caused by the deficiency of glycogen debranching enzyme, encoded by the AGL gene. Two clinical types of the disease are most prevalent: GSD IIIa involves the liver and muscle, whereas IIIb affects only the liver. The classical dietetic management of GSD IIIa involves prevention of fasting, frequent feeds with high complex carbohydrates in small children, and a low-carb-high-protein diet in older children and adults.

Vitamin D Levels and Bone Mineral Density in Inborn Errors of Metabolism Requiring Specialised Diets.

Objective: To evaluate vitamin D levels and bone mineral density in patients with dietary limitations due to inborn errors of metabolism (IEM) and its correlation with diets.

Study Design: Retrospective study.

Place And Duration Of Study: Department of Pediatrics, Division of Pediatric Metabolism and Nutrition, Gazi University Hospital, Turkey, from March to Semtember 2016.

A possible biomarker of neurocytolysis in infantile gangliosidoses: aspartate transaminase.

Gangliosidoses (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.

High incidence of co-existing factors significantly modifying the phenotype in patients with Fabry disease.

Fabry disease results from deficiency of the lysosomal enzyme alpha-galactosidase A. The families of 11 index cases were screened by enzyme and molecular assays. Further clinical and laboratory investigations were carried out in all cases.

Neonatal multiple sulfatase deficiency with a novel mutation and review of the literature.

Multiple sulfatase deficiency is a rare autosomal recessive disorder in which affected individuals present a complex phenotype due to the impaired activity of all sulfatases. There are different types of multiple sulfatase deficiency; among them, the neonatal form is the most severe, with a broad range of mucopolysaccharidosis-like symptoms and death within the first year of life. The disorder is caused by homozygous or compound heterozygous mutations in the sulfatase-modifying factor-1 (SUMF1) gene.

Diagnosis of glycine encephalopathy in a pediatric patient by detection of a GLDC mutation during initial next generation DNA sequencing.

Early diagnosis for metabolic encephalopathy caused by inborn errors of metabolism is very important for the initiation of early treatment and also for prevention of sequela. Metabolic encephalopathy in the form of seizures can result from many inborn errors of metabolism and considering the large number of disorders causing metabolic encephalopathy, enzyme assays or conventional molecular tests are expensive and take considerably long period of time which results in delayed treatment. In our center we have used next generation DNA sequencing technology as an initial diagnostic test to look for about 700 disorders at the same time for the etiologic diagnosis of a 4-month-old female infant suffering from intractable seizures.

Vitamin A status and factors associated in healthy school-age children.

Background & Aims: Vitamin A deficiency (VAD) is one of the most widespread vitamin deficiencies. Vitamin A is essential for children in order to ensure a healthy life span and sustain the normal growth and development. Aim of this study is to examine vitamin A status, and factors associated with it, in healthy school-age children.

Could GSD type I expand the spectrum of disorders with elevated plasma chitotriosidase activity?

Glycogen storage disease type I (GSDI) is characterized by accumulation of glycogen and fat in the liver and kidneys, resulting in hepatomegaly and renomegaly. Human chitotriosidase is a recently described fully active chitinase expressed by activated macrophages. Marked elevation of chitotriosidase activity was initially observed in plasma of patients with Gaucher disease.

Screening for Fabry disease in patients undergoing dialysis for chronic renal failure in Turkey: identification of new case with novel mutation.

Background: Chronic renal failure (CRF) is a serious complication of Fabry disease (FD). The aims of the present study were to determine the prevalence of unrecognized FD in Turkish hemodialysis population and to investigate the molecular background.

Method: Primarily, α-galactosidase A (α-Gal A) activity was investigated on DBS in 1136 patients of both sexes who underwent dialysis for CRF in Turkey.

Asymmetric dimethylarginine (ADMA) and L-arginine levels in children with glycogen storage disease type I.

Patients with glycogen storage disease type I (GSD-I) often have marked hyperlipidemia with abnormal lipoprotein profiles. This metabolic abnormality improves, but is not fully corrected, with dietary therapy; therefore, these patients may be at high risk for the development of atherosclerosis. A recently discussed cardiovascular risk factor, asymmetric dimethylarginine (ADMA), a naturally occuring product of asymmetric methylation of proteins, is an endogenous inhibitor of endothelial nitric oxide synthase.

Assessment of atherosclerosis risk due to the homocysteine-asymmetric dimethylarginine-nitric oxide cascade in children taking antiepileptic drugs.

Purpose: The aim of this study was to assess the atherogenicity risk of antiepileptics in children by investigating the cascade, "hyperhomocysteinemia (HHcy)→asymmetric dimethylarginine (ADMA) increase→nitric oxide (NO) decrease", which is thought to contribute to the developmental process of atherosclerosis.

Methods: The participants included 53 epilepsy patients who received either valproic acid (VPA, n=26) or oxcarbazepine (OXC, n=27). Twenty-four healthy sex- and age-matched children served as controls.