Gastrointestinal Panel Performance for the Diagnosis of Acute Gastroenteritis in Pediatric Patients.

Background: Various methods are used to identify the causative organisms of acute gastroenteritis (AGE) in children. The gastrointestinal (GI) panel has the potential to detect up to 22 pathogens rapidly through the multiplex real-time PCR test. We studied the impact of the GI panel on clinical management in the pediatric population.

To What Extent Does Arginine Reduce the Risk of Developing Necrotizing Enterocolitis?

Necrotizing enterocolitis (NEC) and neonatal sepsis are polar opposite diseases that are commonly encountered in the NICU. Concerning the frequency of these pathologies, NEC is regarded as being a much rarer condition, whereas neonatal sepsis is slightly more commonly encountered. However, neonatal sepsis can present with varying clinical presentations and, if caught late, can be detrimental to the patient.

Fulminant Neonatal Liver Failure in MPV 17-Related Mitochondrial DNA Depletion Syndrome.

Mitochondrial depletion syndromes are well established causes of liver failure in infants. Hepatocerebral variant related to MPV17 gene defect is characterized by infantile onset of progressive liver failure, developmental delay, neurological manifestations, lactic acidosis, hypoglycemia, and mtDNA depletion in liver tissue. We report a hepatocerebral variant of mitochondrial DNA depletion syndrome in a neonate who presented with septic shock picture, hypoglycemia, jaundice, hypotonia, and rotatory nystagmus.

Molecular characterization of CTNS mutations in Tunisian patients with ocular cystinosis.

Background: Ocular cystinosis is a rare autosomal recessive disorder characterized by intralysosomal cystine accumulation in renal, ophthalmic (cornea, conjunctiva), and other organ abnormalities. Patients with ocular cystinosis are mostly asymptomatic and typically experience mild photophobia due to cystine crystals in the cornea observed accidently during a routine ocular examination. The ocular cystinosis is associated with different mutations in CTNS gene.

Clinical outcomes after 4.5 years of eliglustat therapy for Gaucher disease type 1: Phase 3 ENGAGE trial final results.

Eliglustat, an oral substrate reduction therapy, is approved for eligible adults with Gaucher disease type 1. In the Phase 3 ENGAGE trial of previously untreated adults with Gaucher disease type 1, eliglustat-treated patients had statistically significant improvements in organ volumes and hematologic parameters compared with placebo in the 9-month primary analysis. We report final outcomes by time on eliglustat among all patients who participated in the ENGAGE trial and extension.

High Frequency of Cardiovascular Complications in Tunisian Kawasaki Disease Patients: Need for a Further Awareness.

Background: The outcome of Kawasaki disease (KD) depends on cardiovascular complications (CVCs).

Objectives: This study aimed to explore diagnostic features and CVCs in Tunisian patients with KD.

Methods: In total, 33 Tunisian patients (age, 2.

Novel splice site IDUA gene mutation in Tunisian pedigrees with hurler syndrome.

Background: The mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease resulting from the defective activity of the enzyme α-L-iduronidase (IDUA). The disease has three major clinical subtypes (severe Hurler syndrome, intermediate Hurler-Scheie syndrome and attenuated Scheie syndrome). We aim to identify the genetic variants in MPS I patients and to investigate the effect of the novel splice site mutation on splicing of IDUA- mRNA variability using bioinformatics tools.

Outcomes after 18 months of eliglustat therapy in treatment-naïve adults with Gaucher disease type 1: The phase 3 ENGAGE trial.

Eliglustat, an oral substrate reduction therapy, is a first-line treatment for adults with Gaucher disease type 1 (GD1) who are poor, intermediate, or extensive CYP2D6 metabolizers (>90% of patients). In the primary analysis of the Phase 3 ENGAGE trial (NCT00891202), eliglustat treatment for 9 months resulted in significant reductions in spleen and liver volumes and increases in hemoglobin concentration and platelet count compared with placebo. We report 18-month outcomes of patients who entered the trial extension period, in which all patients received eliglustat.

Treatment-naïve Gaucher disease patients achieve therapeutic goals and normalization with velaglucerase alfa by 4years in phase 3 trials.

Gaucher disease is an inherited metabolic disease characterized by β-glucocerebrosidase deficiency and commonly treated with enzyme replacement therapy (ERT). The efficacy of ERT with velaglucerase alfa was assessed based on the achievement of published therapeutic goals and the normalization of disease parameters in 39 treatment-naïve patients with type 1 Gaucher disease, 6 to 62years of age, enrolled in phase 3 clinical trials. After 4years of ERT, therapeutic goals for thrombocytopenia and splenomegaly had been achieved in 100% of patients; goals for anemia and hepatomegaly had been achieved in 95% and 94% of patients, respectively.

Molecular analysis in a GALNS study cohort of 15 Tunisian patients: description of a novel mutation.

Background: Mucopolysaccharidosis type IVA (MPS IVA) is an autosomal recessive disease caused by the deficiency of the lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS). The purpose of this study was to analyze the GALNS mutations and the haplotypes associated.

Methods: Mutation screening of the GALNS gene was performed by direct sequence analysis using DNA samples from 15 unrelated Tunisian MPS IVA patients.

Development of anti-velaglucerase alfa antibodies in clinical trial-treated patients with Gaucher disease.

Anti-drug antibodies may develop with biological therapies, possibly leading to a reduction of treatment efficacy and to allergic and other adverse reactions. Patients with Gaucher disease were tested for anti-drug antibodies every 6 or 12weeks in clinical studies of velaglucerase alfa enzyme replacement therapy, as part of a range of safety endpoints. In 10 studies between April 2004 and March 2015, 289 patients aged 2-84years (median 43years) were assessed for the development of anti-velaglucerase alfa antibodies.

A de-novo large deletion of 2.8 kb produced in the ABCD1 gene causing adrenoleukodystrophy disease.

X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disorder caused by mutations in the ABCD1 gene, which encodes an ATP-binding cassette transporter protein, ALDP. The disease is characterized by increased concentrations of very long chain fatty acids (VLCFAs) in plasma, adrenal, testicular, and nerve tissues. For this study, our objective was to conduct clinical, molecular, and genetic studies of a Tunisian patient with X-ALD.

Cause of death in patients with chronic visceral and chronic neurovisceral acid sphingomyelinase deficiency (Niemann-Pick disease type B and B variant): Literature review and report of new cases.

Background: Acid sphingomyelinase deficiency (ASMD), [Niemann-Pick Disease Types A and B (NPD A and B)], is an inherited metabolic disorder resulting from deficiency of the lysosomal enzyme acid sphingomyelinase. Accumulation of sphingomyelin in hepatocytes, reticuloendothelial cells, and in some cases neurons, results in a progressive multisystem disease that encompasses a broad clinical spectrum of neurological and visceral involvement, including: infantile neurovisceral ASMD (NPD A) that is uniformly fatal by 3years of age; chronic neurovisceral ASMD (intermediate NPD A/B; NPD B variant) that has later symptom onset and slower neurological and visceral disease progression; and chronic visceral ASMD (NPD B) that lacks neurological symptoms but has significant disease-related morbidities in multiple organ systems. The purpose of this study was to characterize disease-related morbidities and causes of death in patients with the chronic visceral and chronic neurovisceral forms of ASMD.

A novel homozygous missense mutation in the insulin receptor gene results in an atypical presentation of Rabson-Mendenhall syndrome.

Leprechaunism (Donohue syndrome) and Rabson-Mendenhall syndrome are caused by mutations in the insulin receptor gene and are associated with extreme insulin resistance. Clinically these syndromes appear to represent points on a continuum of severity of receptor dysfunction, rather than completely distinct syndromes. We investigated a Libyan infant with growth retardation, facial dysmorphism (elfin-like features), acanthosis nigricans and hirsutism.

Genetic basis of cystinosis in Tunisian patients: Identification of novel mutation in CTNS gene.

Nephropathic cystinosis (NC) is an autosomal recessive disorder characterized by defective transport of cystine across the lysosomal membrane and resulting in renal, ophthalmic, and other organ abnormalities. Mutations in the CTNS gene cause a deficiency of the transport protein, cystinosin. This study was performed to investigate mutations of the CTNS gene in three Tunisian families with NC.

[Renal involvement in glycogen storage disease type 1: Practical issues].

Aim: To investigate risk factors of renal complications in glycogen storage disease type I, in order to identify practical implications for renal preservation.

Methods: A retrospective study of 38 patients with glycogen storage disease type I.

Results: The patients studied were 8.

Splicing defects in ABCD1 gene leading to both exon skipping and partial intron retention in X-linked adrenoleukodystrophy Tunisian patient.

X-linked adrenoleukodystrophy (X-ALD) affects the nervous system white matter and adrenal cortex secondary to mutations in the ABCD1 gene that encodes a peroxisomal membrane protein: the adrenoleukodystrophy protein. The disease is characterized by high concentrations of very long-chain fatty acids in plasma, adrenal, testicular and nervous tissues. Various types of mutations have been identified in the ABCD1 gene: point mutations, insertions, and deletions.

Effect of oral eliglustat on splenomegaly in patients with Gaucher disease type 1: the ENGAGE randomized clinical trial.

Importance: Gaucher disease type 1 is characterized by hepatosplenomegaly, anemia, thrombocytopenia, and skeletal disease. A safe, effective oral therapy is needed.

Objective: To determine whether eliglustat, a novel oral substrate reduction therapy, safely reverses clinical manifestations in untreated adults with Gaucher disease type 1.