Pinar Gencpinar

A Novel Homozygous Selenocysteine Insertion Sequence Binding Protein 2 (SECISBP2, SBP2) Gene Mutation in a Turkish Boy

SECISBP2 is an essential factor in selenoprotein synthesis, and its mutations result in a multiorgan syndrome, including abnormal thyroid hormone metabolism. A 10-year-old obese Turkish boy born to consanguineous parents presented with high thyroxine, low triiodothyronine, high reverse triiodothyronine, and normal or slightly elevated thyrotropin. He also had attention-deficit disorder and muscle weakness but no delay in growth or bone age. Sequencing of genomic DNA revealed a novel c.800_801insA, p.K267Kfs*2 mutation, homozygous in the proband and heterozygous in both parents and his brother. Studies showed reduction in several selenoproteins in serum and fibroblasts.

The risk of subsequent epilepsy in children with febrile seizure after 5 years of age

PURPOSEnDespite their age-dependent definition, febrile seizures (FS) may be observed in people of almost any age. The risk of developing unprovoked seizures after an FS is well defined. However, there are limited data about FS starting or persisting after 5 years of age. In the present study, we evaluated patients who developed FS after 5 years of age.nnnMETHODnBetween 2010 and 2014, we prospectively enrolled all patients with FS. We collected demographic and clinical features, radiologic images, electroencephalograms (EEGs), and results of psychomotor development tests and treatment data of the patients. The patients were grouped into two groups. Group 1 consisted of patients who had the first FS after 5 years of age, and group 2 consisted of patients in whom FS persisted after 5 years of age. Fishers exact test and Pearsons chi-square test were used to analyse the study data and derive conclusions.nnnRESULTSnSixty-four patients were enrolled, and afebrile seizure was observed in 12 (18.8%) of them. Nine (14%) patients were diagnosed to have epilepsy in their follow-up examination. Subsequent epilepsy occurrence was independent of gender, mean age, medical history of the patient, family history of epilepsy, presence of afebrile seizure, type of seizure, type of FS, duration of seizure, semiology of seizure, peak fever and EEG and magnetic resonance imaging (MRI) findings in our total cohort. There were no statistical differences between the groups with regard to the occurrence of subsequent afebrile seizure or epilepsy (p>0.5).nnnCONCLUSIONnClose follow-up is important in patients with FS after the age of 5 years. These seizures are generally benign, but tend to recur and increase the risk of development of epilepsy in the patient. Further studies with a larger cohort are warranted to clarify risk factors and incidence of epilepsy in these patients.

Levetiracetam monotherapy for the treatment of infants with epilepsy

PURPOSEnLevetiracetam is a broad-spectrum anti-epileptic drug that is effective against both focal and generalized epilepsies. In this study, we aimed to evaluate the efficacy, tolerability and safety of levetiracetam monotherapy in the management of different seizure types in children with epilepsy under the age of two.nnnMETHODnThis retrospective study was conducted on children with a diagnosis of epilepsy from January 2014 to January 2017. To be included in the study, patients were required to be less than two years of age at the time levetiracetam was initiated as initial monotherapy and to be followed clinically for at least 6 months.nnnRESULTSnOf the 92 patients, 61 (66%) patients were seizure free. Fifty-eight percent of the patients (31 of 53) with focal epilepsy were seizure free and 77% (30 of 39) generalized epilepsy were seizure free. We found that levetiracetam monotherapy was effective in both focal and generalized epilepsy. Levetiracetam monotherapy was significantly more effective in patients with unknown etiologies (pu202f=u202f0.004). Seizure freedom rate under levetiracetam monotherapy was significantly higher in patients with normal psychomotor development (pu202f=u202f0.000). Seizure freedom rate under levetiracetam monotherapy was significantly higher in patients with unknown etiologies and normal psychomotor development. Normal psychomotor development was the strongest predictor of seizure control under levetiracetam monotherapy (ORu202f=u202f6; 95% CIu202f=u202f2.3-16.0; pu202f<u202f0.001). Five children (1%) reported irritability. No hematological or biochemical, or behavioral adverse side effects except irritability were reported in any children. No patient discontinued levetiracetam therapy because of treatment-related side effects.nnnCONCLUSIONnOur study showed levetiracetam to be an effective, well tolerated and safe agent for the treatment of a variety of seizure types and etiologies seen in infants.

Clinical and Genetic Features of Congenital Myasthenic Syndromes due to CHAT Mutations: Case Report and Literature Review

Congenital myasthenic syndromes (CMS) are neuromuscular transmission disorders caused by mutations in genes encoding neuromuscular junction proteins. CMS due to choline acetyltransferase (CHAT) gene is characterized by episodic apnea. We report a case of a 12-month-old female patient presented with recurrent episodic apnea carrying a mutation in CHAT gene, p.I336T. Furthermore, we describe the genetic and clinical findings in 44 CMS patients due to CHAT mutations in the literature up to date. Episodes of apnea and respiratory insufficiency are the hallmarks of CHAT mutations. Clinical manifestations usually provoked by infections and fever. CMS due to CHAT mutations are rare, but it is important to diagnosis. Early diagnosis and appropriate treatment can improve morbidity and mortality.

Tibial nerve axonal excitability in type 1 diabetes mellitus: Axonal Excitability in Diabetes

Introduction: The aim of this study was to determine alterations in axonal excitability in tibial nerve as compared with median nerve axonal excitability in patients with diabetic polyneuropathy. Methods: Six patients with diabetic polyneuropathy and 10 patients with diabetes mellitus without polyneuropathy were enrolled. Results: Compared with diabetic patients without polyneuropathy, the tibial nerve strength–duration time constant was significantly longer and supernormality was lower in those with polyneuropathy. Threshold electrotonus studies showed abnormalities in patients with diabetic polyneuropathy, in which smaller threshold changes from long‐depolarizing and hyperpolarizing conditioning, termed “fanning‐in,” were found. Discussion: This study confirms that axonal excitability is significantly altered in the tibial nerve of patients with diabetic polyneuropathy. Evaluating the axonal excitability of the median and tibial nerves may reveal the presence of length‐dependent polyneuropathy at an early stage. Muscle Nerve 59:76–81, 2019

An unusual cause of cavitating leukoencephalopathy: ethylmalonic encephalopathy

Following a mild head trauma 1 week prior, a 6-year-old girl diagnosed with Leigh syndrome was admitted to our Child Neurology Department due to a loss of reaction to external stimuli and swallowing dysfunction. She was able to walk and began to speak at 30 months of age, but then lost the ability to walk at 5 years old, so she had delays and regressions in development. The previous year, the patient was hospitalized due to acute diarrhea, severe lactic acidosis, and encephalopathy. Plasma ammonia level was normal and she recovered with hydration and bicarbonate replacements. Urine organic acids during this metabolic crisis showed elevated ethylmalonic acid levels (96 mmol/mol/crea; reference range 0–15). The physical examination revealed axial hypotonia, muscle weakness, lower limb spasticity, increased deep tendon reflexes, extensor bilateral plantar reflexes, and clonus. The ophthalmic examination identified bilateral tortuosity in retinal veins. Biochemical blood tests showed mildly elevated plasma lactate and C4-acylcarnitine levels, while serum pyruvate, ammonia, amino acids, and creatine kinase levels were normal. Blood tandem mass spectrometry was normal, but urine organic acid examination revealed a 1.2-fold increase in ethylmalonic acid levels. The electroencephalography record demonstrated diffuse encephalopathy. The electromyography was normal. The brain MRI revealed bilateral hyperintensity in the head of the caudate nucleus, subcortical and deep white matter, and cerebellar white matter. It also showed multiple cavitation foci; diffusion-weighted MRI showed diffusion-restricting lesions. Computerized tomography of the cranium showed calcification of the posterior occipital area (Figs. 1, 2). Genetic tests showed a pathogenic, homozygous, c.3G>T (p.Met1Ile) mutation (rs119103249) in the first codon of ETHE1 gene. Ethylmalonic encephalopathy (EE) is caused by mutations in the ETHE1 gene, which codes a mitochondrial sulfur dioxygenase. Accumulation of hydrogen sulfide is attributable to loss-of-function mutations of ETHE1 gene. Therefore, elevated levels of hydrogen sulfide are responsible for the inhibition of cytochrome c oxidase and degradation of short-chain acyl CoA dehydrogenase subunits in the colonic mucosa, muscle, and brain. Vascular lesions in the skin and other organs are observed due to vasoactive and vasotoxic effects [1]. In the literature, multiple cavitations in relation to EE have been reported as rare. Pigeon et al. reported monochorionic twins diagnosed with EE who had neuroimaging changes affecting the white matter, corpus callosum, and basal ganglia as leukoencephalopathy and cavitation [2]. According to the MRI findings of leukoencephalopathy and multiple cavitations, differential diagnosis should consider diseases related to nuclear mitochondrial defects and the spectrum of white matter lesions in OXPHOS (oxidative phosphorylation)-related disorders, for example, mutations in NDUFS1 with isolated complex I deficiency associated with progressive cavitating leukoencephalopathy (PCL), mutations in LYRM7 with the defect of * Nihal Olgac Dundar nodundar@gmail.com

A De Novo Xp11.23 Duplication in a Girl with a Severe Phenotype: Expanding the Clinical Spectrum

The Xp11.22-p11.23 duplication syndrome was described in 2009 by Giorda et al and is characterized by intellectual disability, speech delay, and electroencephalography anomalies. We report a case of a 23-month-old girl who presented with epilepsy and global developmental delay and who had a small duplication at Xp11.23. The case we present here is the first case showing the clinical features of Xp11.22-p11.23 duplication syndrome only involving synovial sarcoma, X breakpoint ( SSX ) genes: SSX1 , SSX3 , SSX4 , and SSX9 . This case report contributes to an expanding clinical spectrum of Xp11.22-p11.23 duplication syndrome.

P237 Axonal excitability findings in type 1 diabetes mellitus – Median nerve versus tibial nerve comparison

Objective Length dependent peripheral neuropathy is the most common complication of diabetes mellitus (DM). As no curative treatment for diabetic polyneuropathy (DMP) is available, its prevention and early detection is very important. Axonal excitability is defined as the capability of nodal and paranodal pathological changes in DMP. The aim of present study was to determine alterations in axonal excitability findings in tibial nerve by comparing median nerve axonal excitability findings in Type 1 DMP. Methods The total 284 patients, who were followed up for Type 1 DM according to criteria of American Diabetes Association, were screened in this study. Six DMP patients, 10 random non-polyneuropathy cases and 14 healthy control subjects were examined by threshold tracking method (TROND protokol) from median and tibial nerve. Results Even if there is not prominent difference in median nerve axonal excitability studies in PNP and DM patients there was prominent pathological findings in tibial nerve. The strength–duration time constant was significantly longer in DPN Type 1 patients than in normal patients. Supernormality was significantly smaller in DPN patients. Threshold electrotonus studies showed abnormalities in patients with DPN that smaller threshold changes by long depolarizing and hyperpolarizing conditioning current named as “fanning-in”. Conclusion This study confirms that there was significantly alteration in axonal excitability findings in DMP in tibial nerve. Comparisons median and tibial nerve axonal excitability findings have potential to show the length dependent polyneuropathic pathological status in axonal excitability studies.