A Very Rare Etiology of Hypotonia and Seizures: Congenital Glutamine Synthetase Deficiency.

Mutations in the human GLUL gene, which encodes the enzyme glutamine synthetase (GS), may cause congenital glutamine synthetase deficiency. The disease was first described in 2005 and only three patients have been reported to date. We report a fourth patient suffering from congenital GS deficiency who was found to have some distinctive clinical findings. The patient was a 30-month-old girl who was referred to us due to developmental delay and seizures which began at 5 months of age. She was seizure free for 5 months with valproic acid and vigabatrin. At presentation, she was found to have microcephaly and hypotonia. Her plasma glutamine concentration was near normal and she had mild hyperammonemia. Cranial magnetic resonance imaging (MRI) showed mild changes. Whole exome sequencing (WES) revealed a homozygous c.121C > T (p.R41C) (p.Arg41Cys) pathogenic variant of the GLUL gene. The diagnosis of this patient underlines the importance of careful evaluation of patients with borderline low glutamine levels. Treatment was begun with L-glutamine and nicotinamide and biochemical improvements have been observed at 6 months of follow-up. The outcome of this patient may provide important data about the effectiveness of glutamine and nicotinamide treatment in patients with congenital GS deficiency.

Perceptions of patients and their relatives about schadenfreude towards doctors.

Background: Violence in healthcare is a global issue that healthcare professionals experience. The concerning increase in violent incidents in Turkiye particularly makes it a significant problem to explore by examining the underlying psychological factors. In this sense, this study focuses on the concept of Schadenfreude, the malicious joy of someone else's misfortune, towards doctors, which is an under-researched topic in healthcare violence. Particularly, there is a lack of research on patients' and relatives' perceptions of doctors. Objective: This study aims to determine the level of schadenfreude in Turkish society towards the violence experienced by doctors and to develop a model revealing the underlying causes. Methods: Using a convenience sampling method, we recruited 402 participants, who are not first-degree relatives of healthcare professionals, for this quantitative study. For data collection, we developed a survey instrument to measure the level of schadenfreude and six different psychological factors including empathy, sympathy, anger, aggression, and deservingness. For data analysis, we used structural equation modeling. Results: The results showed that the lower the levels of empathy and sympathy towards doctors were, the higher the levels of both schadenfreude and aggression were. Envy had no significant effect on either schadenfreude or aggression, while deservingness directly affected aggression. The perceptions of participants regarding doctors that they deserve violence increased their aggression levels. Schadenfreude had a positive and significant effect on anger and aggression. Implications: The examination of underlying factors of violence towards doctors points to a lack of mutual understanding between patients and doctors. The results of this study indicate a need for increasing empathy towards health professionals by creating societal awareness of their experiences. Local authorities and healthcare organizations can create environments that bring together the public and health professionals to share their experiences with each other or conduct campaigns to draw public attention to the issue. Moreover, training sessions on effective communication can be offered for health professionals to help improve patient-doctor relationships and healthcare outcomes.

Acquired epileptiform opercular syndrome: F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) findings and efficacy of levetiracetam therapy.

We report a five-year-old girl presenting with dysphagia, dysarthria, drooling, and generalized tonic convulsions in whom the final diagnosis was acquired epileptiform opercular syndrome. Levetiracetam monotherapy at a dosage of 40 mg/kg/day improved the clinical findings, and seizures were controlled at the end of the first month of treatment. Six months after the initial diagnosis, she presented with speech deterioration and dysarthria. At this time, although sleep and awake electroencephalography (EEG) were normal, FDG-PET showed hypometabolic and hypermetabolic regions in the anterior/inferior and anterior regions of the right frontal lobe, respectively. By increasing before levetiracetam dosage to 50 mg/kg/day, the clinical findings resolved and the patient is still seizure free. Acquired epileptiform opercular syndrome is a rare epileptic disorder in which the seizures are resistant to conventional antiepileptic drugs. Levetiracetam may be an effective antiepileptic drug in controlling seizures and other clinical findings in acquired opercular epileptiform syndrome. Hypometabolic and hypermetabolic regions in FDG-PET study may be due to ongoing seizure activity or impaired glucose metabolism in this disorder.

Osteopenia in children with cerebral palsy can be treated with oral alendronate.

PURPOSE: Cerebral palsy is one of the most common reasons of osteopenia in childhood. Patients have a significantly decreased bone mineral density, and painful fractures with minor traumas are common. Biphosphonates in the treatment of childhood osteoporosis are increasingly being used. This study aimed to evaluate the efficacy of oral alendronate treatment in children with cerebral palsy. METHODS: Twenty-six children (16 boys and 10 girls) aged 3 to 17 years who had quadriplegic cerebral palsy and osteopenia were included in the study. The patients received alendronate (1 mg/kg/week), calcium (600 mg/day), and vitamin D(3) (400 U/day) over a year. A complete blood count, kidney and liver functional tests, plasma calcium, phosphate and alkaline phosphatase levels, and lumbar vertebral bone mineral density were measured before and after treatment. RESULTS: Compared with pretreatment values, bone mineral density, serum calcium, and phosphate levels of the patients statistically increased and alkaline phosphatase levels decreased after treatment. No patient needed to interrupt treatment because of side effects. CONCLUSIONS: Oral alendronate at a dose of 1 mg/kg/week for the treatment of osteopenia in children with cerebral palsy was found to be safe and effective.

Frequency of Specific Genes in Different Types of Epilepsy.

OBJECTIVE: To determine the diagnostic importance of using an exome-based multigene panel in childhood epilepsy. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Department of Medical Genetics, Diskapi Yildirim Beyazid Training and Research Hospital, from January 2017 to May 2020. METHODOLOGY: The phenotype-genotype relationship was investigated in 35 pediatric patients (aged 18 years or younger) with epilepsy, using a large gene panel comprising 464 epilepsy-related genes. The exome-based panel was used to analyse secondary findings.   Results: The diagnostic yield of the targeted multi-gene panel used was 20% (7/35). The causative genes identified in seven patients (5 boys, 2 girls) were CACNA1E, RELN, PRRT2, TSC1, GABRG2, SCN2A, and SHH. Four of the detected disease-related variants were defined as the novel. Secondary findings in various genes were detected in 19 of the patients. Seven patients with causal genes and the remaining 28 patients were compared in terms of parameters such as gender, mental retardation, developmental retardation, autism, hypotonia, seizure phenotype (only), seizure phenotype (plus), magnetic resonance imaging, degree of kinship of their parents and number of relatives with epilepsy. In addition, patients were evaluated statistically in terms of the same parameters by grouping them according to their gender. There was no statistically significant difference in either study (p >0.05). CONCLUSION: Genetic testing is an important tool for clinicians in determining the diagnosis, management, and treatment strategies of epilepsy patients. Key Words: Epilepsy, Diagnostic yield, Exome-based multigene panel, Next-generation sequencing, Seconder findings.

Neuroleptic malignant syndrome due to risperidone treatment in a child with Joubert syndrome.

Joubert syndrome is a rare autosomal recessive disease characterized by hypotonia, ataxia, episodic hyperpnea, psychomotor retardation, abnormal ocular movements, cerebellar vermian hypoplasia, and molar tooth sign on magnetic resonance imaging. Neuroleptic malignant syndrome is an uncommon and potentially fatal idiosynchratic reaction of antipsychotic drugs, in which the clinical scenario encompass muscular rigidity, hyperthermia, autonomic dysfunction, altered consciousness, high creatinine phosphokinase levels, and leukocytosis. This report describes a case of neuroleptic malignant syndrome due to risperidone in a child with Joubert syndrome.

Benign recurrent abducens (sixth) nerve palsy.

Benign recurrent abducens nerve palsy is rare. Twenty-three cases in children have been reported in the literature and many of these cases followed immunization or were associated with viral illness. Most of the reported patients share the following features: spontaneous recovery within 6 months, ipsilateral recurrence, and painless palsy. The authors describe a Turkish child with recurrent abducens nerve palsy with no obvious etiology.

Evaluation of the relationship between C677T variants of methylenetetrahydrofolate reductase gene and hyperhomocysteinemia in children receiving antiepileptic drug therapy.

Homocysteine (Hcy) is a sulfur-containing amino acid involved in methionine metabolism. Elevated plasma Hcy concentration is a possible risk factor for vascular disease. Folate and vitamin B-12 are vitamins that are necessary for remethylization of Hcy to methionine. The methylenetetrahydrofolate reductase (MTHFR) is the key enzyme in remethylation of Hcy to methionine and supplies the required 5-methyltetrahydrofolate as the methyl donor for this reaction. It is well known that some antiepileptic drugs (AED) can lead to hyperhomocysteinemia by affecting the levels of folate and vitamin B-12. The C677T variant of MTHFR gene can also lead to hyperhomocysteinemia particularly when serum folate level is decreased. In this study, we investigated the levels of serum folate, vitamin B-12 and Hcy in epileptic patients receiving carbamazepine (CBZ) or valproic acid (VPA) as monotherapy, and we also evaluated the probable contribution of the C677T variant of MTHFR gene in hyperhomocysteinemia. A total of 93 patients with idiopathic epilepsy receiving CBZ or VPA as monotherapy were included in this study. CBZ and VPA groups consisted of 29 and 64 patients, respectively. The control group comprised 62 healthy children. We measured serum folate, vitamin B-12 and Hcy levels in each group. We found that mean serum folate level was statistically lower and mean Hcy level was higher in epileptic patients receiving CBZ or VPA when compared with those of controls'. We also determined the C677T variants of MTHFR gene (as normal, heterozygote or homozygote) in epileptic patients. We compared the variant groups for serum folate, vitamin B-12 and Hcy levels and found no significant differences among them. In conclusion, C677T variants of MTHFR gene have no contribution in hyperhomocysteinemia in epileptic patients receiving CBZ or VPA.

Visual and brainstem auditory evoked potentials in children with headache.

BACKGROUND: Headache is a common problem in the pediatric population. The purpose of the present study was to evaluate visual evoked potentials (VEP) and brainstem auditory evoked potentials (BAEP) in children with headache. METHODS: Thirty-seven children fulfilling the International Headache Society Criteria for a diagnosis of migraine, 35 children with tension-type headache and 40 healthy children (control group) were enrolled in the study. RESULTS: The mean age of patients and controls was 10.4 years. P100 latency and amplitudes of migraine patients were significantly higher than children with tension-type headache and control subjects. Children with tension-type headache also had higher P100 latency and amplitude values than control subjects but there was no statistical difference. BAEP responses were similar between all groups. CONCLUSION: Measurement of VEP latency and amplitude is a valuable and reliable test for the diagnosis of migraine and can be used safely in childhood.

Aicardi syndrome: an unusual case associated with pineal gland cyst and ventricular septal defect.

Aicardi syndrome is a cerebroretinal disorder consisting of a heterogeneous spectrum of clinical findings that includes the triad of infantile spasms, agenesis of the corpus callosum, and chorioretinal lacunae. This report describes a 6-month-old girl who has all of the essential features suggestive of Aicardi syndrome, as well as a pineal gland cyst and ventricular septal defect. Although the characteristic features of Aicardi syndrome have been described, its association with pineal gland cyst and ventricular septal defect has not been reported in the literature.

Serum and liver tissue biotinidase enzyme activity in rats which were administrated to valproic acid.

Valproic acid (VPA) is an antiepileptic drug widely used and well-tolerated by most of patients. Its non-dose-dependent side effects seen mostly are the temporary gastrointestinal disturbances including anorexia and nausea, and hepatoxicity. As to its dose-dependent side effects are the weight loss, tremor, skin eruption and the alopecia. In this study we aimed to put forward the biotinidase deficiency considered as a possible cause of alopecia in the rats administered with valproic acid, and the correlation between liver and serum biotinidase enzyme activities (BEA) and transaminases, albumin and serum valproic acid levels. In our study, 4 groups of which one of them was a control group, each consisting of 15 male Wistar rats was organized. 200, 400, and 600 mg/kg/day of VPA, and distilled water, two divided doses per day, were administered per orally to VPA-1, VPA-2, VPA-3, and control group, respectively, in 60 days. Their serum and liver biotinidase enzyme activities, serum AST, ALT, albumin, and valproic acid levels were measured. Alopecia was seen in the subjects of 6.6% of VPA-1, 13.3% of VPA-2, and 26.6% of VPA-3. Significant difference in the liver tissues BEA was noted only between VPA-3 and the control group. Reductions were observed both in the liver tissues BEA and the serum BEA levels, which are inversely proportional to the VPA doses. A positive correlation between the liver biotinidase enzyme activities and the serum valproic acid levels, and the negative correlation between the liver tissues biotinidase activities and the serum valproic acid levels were noted, respectively. As a conclusion, the partial alopecia which is an initial symptom of reduced biotinidase activity may also be created depending on the reduction of biotinidase activity during valproic acid therapy. The alopecia which may further be observed in the patients receiving valproic acid therapy may be prevented by means of administration of biotin in a dose of 10 mg/day.

Stroke associated with pseudoephedrine in a child with rhabdomyosarcoma.

Pseudoephedrine is a nasal vasoconstrictor and is contained in many cough and cold medications. It is generally harmless when used in recommended doses. Hypertensive crisis, psychosis, hemorrhagic stroke, and intracranial hemorrhage have been reported as severe complications. We report a 4-year-old girl with nasopharyngeal rhabdomyosarcoma who developed stroke while on pseudoephedrine therapy for 3 days and had no hematological abnormalities.

Effects of iron deficiency versus iron deficiency anemia on brainstem auditory evoked potentials in infancy.

There has been little or no evidence of brainstem auditory evoked potentials (BAEPs) among infants with iron deficiency (ID) that is not severe enough to cause anemia. To our knowledge, the effect of ID on auditory functions and/or potentials has not been investigated previously, though it seems reasonable that it should be associated with BAEP measures intermediate between those observed in iron deficiency anemia (IDA) and in iron sufficiency, considering the role of iron in myelin formation and maintenance. We therefore aimed in this study to investigate the effect of ID on BAEPs by comparing three groups of infants with ID, IDA and iron sufficiency (control) both before and after iron treatment (in iron-deficient groups). Three groups of infants (IDA, n = 25; ID, n = 24; Control, n = 44) were compared on the basis of hematological laboratory parameters and BAEP measurements both at entry into and after (12 weeks treatment with oral iron in IDA and ID groups) the study. BAEP measurements recorded at 85 dB both at entry into and after the study were not significantly different among the groups, although a sufficient response to iron treatment was achieved in iron-deficient groups (Group I and Group II). The only positive finding determined in our study was a slight decrease in latencies obtained at the end of the study when compared to the pre-study values in all three groups of the study in accordance with the expected age-dependent developmental changes. Although no negative electrophysiological effect of ID on brainstem auditory functions was found in the present study, further longer term (late childhood or adult) studies are necessary to elucidate the relationships among anemia (maybe other than IDA), ID and auditory functions, and clinical implications of hearing loss (if any) should be questioned.

Caudothalamic groove cysts in Zellweger syndrome.

The cerebro-hepato-renal syndrome of Zellweger is the most severe peroxisome biogenesis disorder. Zellweger syndrome is caused by a disturbance in the peroxisomal protein import machinery and leads to multiple organ defects and death usually within the first year of life. Here we report a 3-month-old girl with Zellweger syndrome who was found to have cysts in the caudothalamic groove on cranial magnetic resonance imaging.

Evaluation of visual evoked potentials in children with headache.

Headache is a common problem in childhood. Visual evoked potential (VEP) P100 latencies were recorded in children with headache. Sixty-four patients, aged 10.7 +/- 1.2 years, met the criteria of the International Headache Society for the diagnosis of migraine. Fifty-eight patients, aged 10.2 +/- 1.3 years, with tension headache and 56 healthy subjects, aged 10.3 +/- 1.3 years, as the control group were also studied. Patients with migraine had slightly longer P100 latencies than the other two groups. We conclude that VEP latency recording is a valuable test in the diagnosis of migraine, and can be safely used in children.

Unilateral split foot, torticollis, congenital heart defect and hydrocephaly: a new syndrome?

We report a patient showing unilateral split foot together with unusual malformations.

Acrocallosal syndrome: report of five Turkish patients.

Acrocallosal syndrome is characterized by agenesis of the corpus callosum, craniofacial anomalies, psychomotor retardation, and polydactyly. The clinical spectrum of this syndrome is broader than previous reports suggest. Five Turkish patients including dizygotic twins are reported.

Evaluation of bone mineral density in children with cerebral palsy.

In the present study, bone mineral density of 40 children with cerebral palsy (study group) and the effects of various risk factors on bone mineralization in these children were investigated by comparing with 40 age-matched healthy children (control group). Weight, height, skinfold thickness, body-mass index measurements, and serum levels of calcium, phosphorus, alkaline phosphatase and 25 OH vitamin D were not significantly different between the study and control groups (p>0.05). The mean bone mineral density value of the study group measured by dual-energy X-ray absorptiometry method at L2-L4 levels of lumbar vertebrae was significantly lower than that of the control group (p<0.05). When the patients in the study group were assessed with respect to ambulation status, pattern of involvement, calcium and energy intakes, and whether or not they had taken and/or were taking a regular physical therapy program, there was a significant difference only between the hemiplegic and tetraplegic patients (p<0.05), while there were no significant differences among the patients who were ambulant versus non-ambulant, who had sufficient versus insufficient calcium and energy intakes, and who did and did not take a regular physical therapy (p>0.05). Although the ambulatory status, quantity of calcium and energy intakes, and the presence or absence of a physical therapy program had no effects on bone mineral density values of the children with cerebral palsy in this study, the exact factors and mechanisms responsible for the reduced bone mineral density in children with cerebral palsy should be investigated in further large-scale studies considering the increased risk of pathological fractures in these patients.

Breath-holding spells may be associated with maturational delay in myelination of brain stem.

PURPOSE: To evaluate possible contribution of maturational delay of brain stem in the etiology of breath-holding spells in children using brain stem auditory evoked potentials. METHODS: The study group included children who experienced breath-holding spells. The control group consisted of healthy age- and sex-matched children. Age, gender, type and frequency of spell, hemoglobin, and ferritin levels in study group and brain stem auditory evoked potentials results in both groups were recorded. Study group was statistically compared with control group for brain stem auditory evoked potentials. RESULTS: The mean age of study and control groups was 26.3 ± 14.6 and 28.9 ± 13.9 months, respectively. The III-V and I-V interpeak latencies were significantly prolonged in the study group compared with the control group (2.07 ± 0.2 milliseconds; 1.92 ± 0.13 milliseconds and 4.00 ± 0.27 milliseconds; 3.83 ± 0.19 milliseconds; P = 0.009 and P = 0.03, respectively). At the same time, III-V and I-V interpeak latencies of patients without anemia in the study group compared with those of control group were significantly prolonged (2.09 ± 0.24 milliseconds; 1.92 ± 0.13 milliseconds and 4.04 ± 0.28 milliseconds; 3.83 ± 0.19 milliseconds; P = 0.007 and P = 0.01, respectively). CONCLUSIONS: Our results consider that maturational delay in myelination of brain stem may have a role in the etiology of breath-holding spells in children.