Melis Köse

Two novel mutations in acid α-glucosidase gene in two patients with Pompe disease.

Abstract Pompe disease is an autosomal recessive lysosomal glycogen storage disorder (GSD) caused by acid α-glucosidase (GAA) deficiency. Pompe disease has a broad genotypic and phenotypic spectrum. The infantile-onset form is the most severe form and presents with hypotonia and cardiomyopathy in early infancy. The probands who died were found to have GSD type II based on clinical and biochemical findings. We report two families with Pompe disease in whom the parents’ molecular analysis revealed two novel mutations: c.2045A>G (p.Q682R) and c.763C>T (p.Q255X).

The second case of saposin a deficiency and altered autophagy

Krabbe disease is a lysosomal storage disease caused by galactosylceramidase deficiency, resulting in neurodegeneration with a rapid clinical downhill course within the first months of life in the classic infantile form. This process may be triggered by the accumulation of galactosylceramide (GalCer) in nervous tissues. Both the enzyme galactosylceramidase and its in vivo activator molecule, saposin A, are essential during GalCer degradation. A clinical manifestation almost identical to Krabbe disease is observed when, instead of the galactosylceramidase protein, the saposin A molecule is defective. Saposin A results from posttranslational processing of the precursor molecule, prosaposin, encoded by the PSAP gene. Clinical and neuroimaging findings in a 7-month-old child strongly suggested Krabbe disease, but this condition was excluded by enzymatic and genetic testing. However, at whole exome sequencing, the previously undescribed homozygous, obviously pathogenic PSAP gene NM_002778.3:c.209T>G(p.Val70Gly) variant was determined in the saposin A domain of the PSAP gene. Fibroblast studies showed GalCer accumulation and the activation of autophagy for the first time in a case of human saposin A deficiency. Our patient represents the second known case in the literature and provides new information concerning the pathophysiology of saposin A deficiency and its intralysosomal effects.

Evaluation of Cardiovascular Involvement and Cytokine Levels in Patients with Mucopolysaccharidosis

Ad dress for Cor res pon den ce Ebru Canda MD, Ege University Faculty of Medicine, Department of Pediatrics, Division of Metabolism and Nutrition, İzmir, Turkey Phone: +90 232 290 12 45 E-mail: ebru.canda@gmail.com ORCID ID: orcid.org/0000-0002-9175-1998 Re cei ved: 07.10.2018 Ac cep ted: 17.10.2018 1Ege University Faculty of Medicine, Department of Pediatrics, Division of Metabolism and Nutrition, İzmir, Turkey 2Ege University Faculty of Medicine, Department of Biochemistry, İzmir, Turkey 3Ege University Faculty of Medicine, Department of Pediatrics, Division of Cardiology, İzmir, Turkey Ebru Canda1, Melis Köse1, Mehtap Kağnıcı1, Meral Dondurmacı2, Sema Kalkan Uçar1, Eser Sözmen2, Reşit Ertürk Levent3, Mahmut Çöker1

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

39 ©Copyright 2018 by Ege University Faculty of Medicine, Department of Pediatrics and Ege Children’s Foundation The Journal of Pediatric Research, published by Galenos Publishing House. Ad dress for Cor res pon den ce Ebru Canda MD, Ege University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Metabolism and Nutrition, İzmir, Turkey Phone: +90 505 525 29 16 E-mail: ebru.canda@gmail.com ORCID ID: orcid.org/0000-0002-9175-1998 Re cei ved: 06.11.2017 Ac cep ted: 25.12.2017 1Ege University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Metabolism and Nutrition, İzmir, Turkey 2Ege University Faculty of Medicine, Department of Radiology, İzmir, Turkey 3Ege University Faculty of Medicine, Department of Biochemistry, İzmir, Turkey 4Ege University Faculty of Medicine, Department of Genetics, İzmir, Turkey Ebru Canda1, Melis Köse1, Havva Yazıcı1, Esra Er1, Cenk Eraslan2, Sema Kalkan Uçar1, Sara Habif3, Emin Karaca4, Hüseyin Onay4, Ferda Özkınay4, Mahmut Çoker4

Single center experience of biotinidase deficiency: 259 patients and six novel mutations.

Abstract Background Biotinidase deficiency (BD) is an autosomal recessively inherited disorder of biotin recycling. It is classified into two levels based on the biotinidase enzyme activity: partial deficiency (10%–30% enzyme activity) and profound deficiency (0%–10% enzyme activity). The aims of this study were to evaluate our patients with BD, identify the spectrum of biotinidase (BTD) gene mutations in Turkish patients and to determine the clinical and laboratory findings of our patients and their follow-up period. Methods A total of 259 patients who were diagnosed with BD were enrolled in the study. One hundred and forty-eight patients were male (57.1%), and 111 patients were female (42.9%). Results The number of patients detected by newborn screening was 221 (85.3%). By family screening, 31 (12%) patients were diagnosed with BD. Seven patients (2.7%) had different initial complaints and were diagnosed with BD. Partial BD was detected in 186 (71.8%) patients, and the profound deficiency was detected in 73 (28.2%) patients. Most of our patients were asymptomatic. The most commonly found variants were p.D444H, p.R157H, c.98_104delinsTCC. The novel mutations which were detected in this study are p.D401N(c.1201G>A), p.A82G (c.245C>G), p.F128S(c.383T>C), c617_619del/TTG (p.Val207del), p.A287T(c.859G>A), p.S491H(c.1471A>G). The most common mutation was p.R157H in profound BD and p.D444H in partial BD. All diagnosed patients were treated with biotin. Conclusions The diagnosis of BD should be based on plasma biotinidase activity and molecular analysis. We determined the clinical and genetic spectra of a large group of patients with BD from Western Turkey. The frequent mutations in our study were similar to the literature. In this study, six novel mutations were described.

Coexistence of Gaucher Disease and severe congenital neutropenia

Gaucher Disease (GD) is the most common lysosomal storage disorder has traditionally been classified into three clinical phenotypes. Type 3 GD is characterized by neurological involvement but neurological symptoms generally appear later in life than in type 2 disease. Neutropenia is much rarer than other hematological manifestations in GD and has not been scrutinized adequately. Severe congenital neutropenia (SCN) is a rare disease entity which is characterized by a paucity of peripherally circulating neutrophils with arrest of neutrophil maturation at the promyelocyte stage and consequent increased susceptibility to severe and recurrent infections. We report a patient who presented in the first year of life with visceral involvement and severe neutropenia in whom the propositus had a unique coexistence of Gaucher Disease and severe congenital neutropenia associated with a mutation in HAX1. In contrast to his expired siblings he had experienced no severe infections. These clinical observations suggest that enzyme replacement therapy may display a modulating factor with respect to the clinical course of SCN. SYNOPSIS: Our patient is the only report of the combination of Gaucher Disease and Kostmann Syndrome in the literature. The clinical course of our patient is not severe when comparing with exitus siblings and other Kostmann Syndrome patients. But when considering the patients only clinical difference is ERT, this case is very important to emphasise the role of enzyme replacement therapy in bone marrow.

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 treatments efficacy when extracorporeal procedures are not available due to technical difficulties during attack period of the disease.