Effectiveness of Valproic Acid in the Treatment of Sydenham's Chorea and a Literature Review.

There is still no evidence-based guideline and consensus on the treatment Sydenham's Chorea (SC). The first-line medication preference of specialists depends on personal experience and is variable. In this study, we evaluate the treatment results of pediatric patients who were treated with valproic acid (VPA). The medical records of 17 patients diagnosed with SC were reviewed retrospectively. The mean time to clinical improvement was found as approximately 5 days, the mean duration of remission as 13.60 ± 3.94 weeks and the mean duration of medication use was found as 17.96 ± 3.81 weeks. No side effects were observed in any of the patients and relapse occurred in 2 patients. A positive correlation was found between the initial C-reactive protein (CRP) level and the duration of medication use. Until evidence-based guidelines are established, VPA can be used as an effective, safe, and inexpensive first-line treatment option, especially in pediatric patients.

Clinical and Genetic Spectrum of Myotonia Congenita in Turkish Children.

BACKGROUND: Myotonia congenita is the most common form of nondystrophic myotonia and is caused by Mendelian inherited mutations in the CLCN1 gene encoding the voltage-gated chloride channel of skeletal muscle. OBJECTIVE: The study aimed to describe the clinical and genetic spectrum of Myotonia congenita in a large pediatric cohort. METHODS: Demographic, genetic, and clinical data of the patients aged under 18 years at time of first clinical attendance from 11 centers in different geographical regions of Türkiye were retrospectively investigated. RESULTS: Fifty-four patients (mean age:15.2 years (±5.5), 76% males, with 85% Becker, 15% Thomsen form) from 40 families were included. Consanguineous marriage rate was 67%. 70.5% of patients had a family member with Myotonia congenita. The mean age of disease onset was 5.7 (±4.9) years. Overall 23 different mutations (2/23 were novel) were detected in 52 patients, and large exon deletions were identified in two siblings. Thomsen and Becker forms were observed concomitantly in one family. Carbamazepine (46.3%), mexiletine (27.8%), phenytoin (9.3%) were preferred for treatment. CONCLUSIONS: The clinical and genetic heterogeneity, as well as the limited response to current treatment options, constitutes an ongoing challenge. In our cohort, recessive Myotonia congenita was more frequent and novel mutations will contribute to the literature.

A case with congenital disorder of glycosylation with defective fucosylation 2 and new mutation in FUK gene.

INTRODUCTION: Congenital disorders of glycosylation (CDG) is a group of rare, hereditary, multisystem disorders, predominantly affecting nervous system. There are N- and O- types of glycosylation. Fucosylation, a form of N-glycosylation, involves many enzymes. Until today, type 1 and type 2 fucosylation defects were identified, having pathogenic variants in genes encoding α-1,6-fucosyltransferase and fucokinase enzymes, respectively. In this article, a patient with type 2 fucosylation defect will be presented, with hypotonia, developmental delay and blindness and a pathogenic variant that was previously described in two patients. METHOD: Whole exome sequencing (WES) was performed, since the patient had no time to implement diagnostic algorithm for hypotonia etiology. RESULTS: WES revealed a new pathogenic variant of homozygous c.993_1011del (p.Glu335Hisfs*55) frameshift variant of the FUK gene NM_145059 transcript. She had milder clinical manifestation than reported two patients. CONCLUSION: Congenital Defect of Glycosylation should be considered when the clinical findings cannot be explained by other known diseases, particularly in patients with multisystemic, predominantly neurological involvement.

The Importance of Neurological Examination for the Indication of Computed Tomography of the Brain in Pediatric Emergency Room.

OBJECTIVES: In this study, records of the children who underwent Computed Tomography of the Brain (CTB) were reviewed to increase the awareness of pediatricians to protect patients from radiation, whether CTB was used with right indications or if it was determinative for diagnosis. METHODS: In total, in this study, 342 cases applied to our Pediatric Emergency Polyclinic between January 2005-December 2010 were retrospectively evaluated regarding complaints at admission, neurological examination and CTB results. The sensitivity and specificity of the neurological examination in detecting the CTB pathology was determined. RESULTS: The results were normal in 319 of the 342 cases with CBT and abnormal in 23, out of which abnormal CTB results were only in three (0.99%) of the 301 patients with normal neurological examination results and in 20 (48.8%) of 41 patients with abnormal neurological examination results. The difference between the two groups was statistically significant (p=0.001). The sensitivity and specificity of the neurological examination in detecting CTB pathology were 87% and 94%, respectively. CONCLUSION: Detailed neurological examination of the patients in the pediatric emergency department has a key role in determining the indications for CTB. Clinical follow-up should guide neuroradiological imaging in children with normal results of the neurological examination.

Congenital myotonia: a review of twenty cases and a new splice-site mutation in the CLCN1 gene.

BACKGROUND AND OBJECTIVES: Congenital Myotonia (CM) is a disease caused by mutations in the skeletal muscle chloride channel gene (CLCN1). Mutations can be transmitted as autosomal dominant (Thomsen's disease) or recessive (Becker's disease). CM is more common in men and Becker myotonia may be 10 times more common than Thomsen myotonia. Genotypic and phenotypic characteristics of CM may vary according to geographical region and ethnicity. METHOD: In this study, we present the genotypic and phenotypic characteristics of 20 Turkish CM patients all diagnosed by molecular genetic testing. The clinical and laboratory features of the patients with mutation in CLCN1 gene were retrospectively analyzed. RESULTS: Eleven of the patients were female. c.1064+1G > A splice-site change, p.Arg338X (c.1012 C > T) stop codon, p.Gly190Ser (c.568_569delinsTC) missense mutations were detected. Eight of the 20 patients were found to be compatible with Becker type and 12 with Thomsen type, based on mode of inheritance, neurological examination findings and genetic test results. CONCLUSION: The c.1064+1G > A splice-site change mutation, defined for the first time in this study, expands the spectrum of mutations in the CLCN1 gene. Thomsen type and female gender were observed to be more frequent in this series of patients from Turkey.

A rare cause of epileptic encephalopathy: a beta-propeller protein associated neurodegeneration case with a new mutation and literature review.

In this report, detailed clinical features of a female patient and a new mutation that was not previously identified in the WD repeat-containing protein 45 (WDR45) gene are presented in order to contribute to the information in the literature on the phenotype as well as genotype of Beta-Propeller Protein Associated Neurodegeneration. Whole Exome Sequencing (WES) analysis was done since etiology could not be determined. Our case was admitted to the hospital due to epilepsy, growth retardation and autism. Her family history was unremarkable except consanguineous marriage. She had tonic seizures twice at the age of 7 and 12 months and had continual seizures after 16 months. At the time, electroencephalography and brain MRI were performed twice were determined to be normal. Brain MRI Spectroscopy was also found to be normal at 35 months of age. Metabolic screening tests (acyl carnitine profile, urine organic acids, plasma amino acids, a very long chain fatty acid profile, etc.) were also normal. Genetic screening of the epilepsy panel for epileptic encephalopathies was negative. WES analysis revealed heterozygous previously unreported variant in intron 6 of the WDR45 gene, c.344+5G > A. In conclusion; Beta-Propeller Protein Associated Neurodegeneration should be considered as an option in the diagnosis of female patients with clinical findings of epilepsy, growth retardation and autism, with unspecified etiology.

A rare cause of epileptic encephalopathy: a beta-propeller protein associated neurodegeneration case with a new mutation and literature review.

In this report, detailed clinical features of a female patient and a new mutation that was not previously identified in the WD repeat-containing protein 45 (WDR45) gene are presented in order to contribute to the information in the literature on the phenotype as well as genotype of Beta-Propeller Protein Associated Neurodegeneration. Whole Exome Sequencing (WES) analysis was done since etiology could not be determined. Our case was admitted to the hospital due to epilepsy, growth retardation and autism. Her family history was unremarkable except consanguineous marriage. She had tonic seizures twice at the age of 7 and 12 months and had continual seizures after 16 months. At the time, electroencephalography and brain MRI were performed twice were determined to be normal. Brain MRI Spectroscopy was also found to be normal at 35 months of age. Metabolic screening tests (acyl carnitine profile, urine organic acids, plasma amino acids, a very long chain fatty acid profile, etc.) were also normal. Genetic screening of the epilepsy panel for epileptic encephalopathies was negative. WES analysis revealed heterozygous previously unreported variant in intron 6 of the WDR45 gene, c.344+5G > A. In conclusion; Beta-Propeller Protein Associated Neurodegeneration should be considered as an option in the diagnosis of female patients with clinical findings of epilepsy, growth retardation and autism, with unspecified etiology.

Cardiac evaluation in children with malnutrition.

AIM: The main purpose of this study was to identify myocardial changes in malnourished children. MATERIAL AND METHODS: This prospective study included 47 patients with malnutrition and 44 healthy controls. The subjects who had malnutrition were classified according to the method of Gomez and Waterlow. Electrocardiographic and echocardiographic examinations, 24-h Holter monitoring, and biochemical assessments were performed in all subjects. RESULTS: The malnutrition group included 20 (42.5%) males, and the control group included 19 (43.1%) males (p<0.05). There was no difference between the malnutrition and control groups with regard to mean age (69.4±57.3 months and 68.9±48.2 months, respectively, p=0.5). Although the left ventricular mass was lower in the patient group compared with the control group, the left ventricular mass index was not different (42.3±24.5 g, 53.4±23.9 g, p=0.049 and 60.7±13.3 g/m2, 61.9±12.1 g/m2, p=0.67, respectively). The left ventricular ejection fraction and fractional shortening were lower in the patient group compared with the control group (66.2±5.3%, 69.2±4.07%, p=0.04 and 35.4±4.2%, 37.9±3.4%, p=0.03, respectively). The myocardial performance index was higher in the patient group (0.45±0.09, 0.36±0.05, respectively, p=0.001). The deterioration of cardiac functions was associated with the severity and duration of malnutrition. Troponin concentrations were not elevated in any patients. The corrected QT dispersion was significantly higher in patients with malnutrition (47.9±16.8, 32.9±10.6, respectively, p=0.001). Complex ventricular arrhythmias were not noted in any patients. CONCLUSION: The malnourished children in this study exhibited impairment in the functions of cardiac contraction including mainly systolic functions and in cardiac conduction system. Cardiac morbidity and mortality can be prevented by early detection and treatment of malnutrition in these patients.

Early neurological complications in children with classical galactosemia and p.gln188arg mutation.

BACKGROUND: Despite implementation of a controlled diet, children with classical galactosemia (CG) may develop a variety of developmental and cognitive problems. In this study, we examined the early developmental status of, as well as the neurological and neuroradiological findings for, children with CG. METHODS: We retrospectively evaluated 46 galactosemia patients who were followed between 2003 and 2017. We included those who exhibited CG and p.gln188arg homozygous mutation without concomitant disease and who had undergone detailed neurological examination, brain magnetic resonance imaging (MRI), and Denver II developmental testing. RESULTS: The mean ages at the time of the most recent neurological examination and Denver II testing were 48.5 ±â€¯28.5 months and 34.4 ±â€¯18.2 months, respectively. Developmental delay was defined as developmental age ≥ 20% lower than chronological age. The results were normal in 25 patients and delayed ≥ 20% in least in one domain, primarily in language development, in 21 patients. Brain MRI was abnormal in 22 patients. CONCLUSIONS: This analysis of the youngest children with the same genetic mutation reported thus far showed that, despite treatment, developmental delays and abnormalities on brain MRI may begin at an early age.

Short-term results of continuous venovenous haemodiafiltration versus peritoneal dialysis in 40 neonates with inborn errors of metabolism.

Several recent studies have reported that toxic metabolites accumulated in the body as a product of inborn errors of metabolism (IEM) are eliminated more rapidly with continuous venovenous hemodiafiltration (CVVHDF) than with peritoneal dialysis (PD). However, there is still uncertainty about the impacts of dialysis modalities on the short-term outcome. Here, it was aimed to investigate the effects of dialysis modalities on the short-term outcome. This retrospective study included 40 newborn infants who underwent PD (29 patients) or CVVHDF (11 patients) due to inborn errors of metabolism at a tertiary centre, between June 2013 and March 2018. The outcomes and the potential effects of the dialysis modality were evaluated. Of 40 patients, 21 were urea cycle defect, 14 were organic academia, and 5 were maple syrup urine disease. The median 50% reduction time of toxic metabolites were shorter in patients treated with CVVHDF (p < 0.05). Catheter blockage was the most common complication observed in PD group (24.1%), whereas in CVVHDF group hypotension and filter blockage were more common. There was no significant difference in mortality between dialysis groups (38% vs. 45.4%, p > 0.05). In patients with hyperammonaemia, duration of plasma ammonia > 200 µg/dL was the most important factor influencing mortality (OR 1.05, CI 1.01-1.09, p = 0.007).Conclusion: This study showed that CVVHDF is more efficient than PD to rapidly eliminate toxic metabolites caused by IEM in newborn infants, but not in improving survival. What is Known: •Toxic metabolites are eliminated more rapidly with CVVHDF than with PD. •Higher complication rates were reported with rigid peritoneal catheters in PD and catheter blockage in CVVHDF. What is New: •Prolonged duration of plasma ammonia levels above a safe limit (200 µg/dL) was associated with increased mortality. •Lower catheter-related complication rates may have been associated with the use of Tenckhoff catheters in PD and the use of right internal jugular vein in CVVHDF.

Efficacy of peritoneal dialysis in neonates presenting with hyperammonaemia due to urea cycle defects and organic acidaemia.

AIM: Newborns with inborn errors of metabolism can present with hyperammonaemic coma. In this study, we evaluated the effect of peritoneal dialysis on plasma ammonium levels and on the short-term outcome in neonatal patients with urea cycle defects and organic acidaemia. METHODS: Data from infants with hyperammonaemia due to urea cycle defects or organic acidaemia treated with dialysis were collected and retrospectively analyzed. The results of patient groups (group I, survived; and group II, died) were compared. RESULTS: Fourteen neonates were enrolled in this study. In group I, plasma ammonium levels before dialysis were median (IQR) 1652 µg/dL (1165-2098 µg/dL); in group II, they were 1289 µg/dL (1070-5550 µg/dL). There was no statistically significant difference. Urea cycle defects were diagnosed in eight, and organic acidaemia in six patients. The duration of a blood ammonia level >200 µg/dL was longer in group II (P = 0.04). A <60.8% decline in the ammonia level from the beginning of dialysis to the 12th hour of dialysis carried a 3.33-fold higher risk of mortality, when compared with a greater decline. Five patients with urea cycle defects, and one with organic acidaemia, died. The mortality risk was 8.33-fold (95% CI = 0.63-90.86) higher for patients with urea cycle defects than for those with organic acidaemia. CONCLUSION: In patients with hyperammonaemia treated with peritoneal dialysis, the rate of ammonia removal and the underlying aetiology appear to be important prognostic factors. Neonates with organic acidaemia who are admitted to centres without continuous renal replacement therapy facilities can be effectively treated with peritoneal dialysis.

A Case of Wernicke Encephalopathy Developing After Ileal Bypass Surgery.

Wernicke encephalopathy is an acute neurological problem resulting from thiamine deficiency and manifesting with mental confusion, oculomotor dysfunction, and ataxia. It is associated with alcohol dependence in adults. Preparatory factors include hyperemesis gravidarum, prolonged diarrhea, prolonged parental nutrition without vitamin support, absorption disorders, anorexia, cancer, and chemotherapy. Failure to consider the clinical findings and preparatory factors of this disease, which is rare in children, can delay diagnosis. This report describes a case of Wernicke encephalopathy developing in a patient with brid ileus and receiving total parenteral nutrition after partial ileal bypass surgery. The patient's clinical and cranial magnetic resonance findings were compatible with Wernicke encephalopathy. Although these are not widespread, typical ocular findings for Wernicke encephalopathy were present. Dramatic improvements were observed in clinical, ocular, and cranial magnetic resonance findings after treatment.

Folate deficiency in patients with classical galactosemia: A novel finding that needs to be considered for dietary treatments.

Çelik M, Özgün N, Akdeniz O, Fidan M, Tüzün H, Ipek MS, Emecan M, Eminoglu FT. Folate deficiency in patients with classical galactosemia: A novel finding that needs to be considered for dietary treatments. Turk J Pediatr 2018; 60: 540-546. The objectives of the study were to assess folate deficiency in patients with classic galactosemia, and to determine whether folic acid supplementation has an effect on galactose-1-phosphate uridyltransferase enzyme activity. Sixty-one newborn infants diagnosed with classic galactosemia between 2010 and 2017 were retrospectively evaluated. Within this group, 48 patients with Q188R homozygous mutation alone were enrolled into the study. Serum folate concentration was studied using chemiluminescence; and in folate deficient patients, galactose-1-phosphate uridyltransferase measurements before and after folic acid supplementation (100 mg/day folic acid for 30 days) were performed using an enzymatic calorimetric measurement technique based on kinetics. The serum folate level was low ( < 4 ng/ml) in 12 patients (25%). The galactose-1-phosphate uridyltransferase enzyme activity after folic acid supplementation was significantly higher than the values before folic acid supplementation (1.00±0.19 U/g Hb vs. 0.74±0.23 U/g Hb, p < 0.05); but was still less than the normal levels. Folate deficiency, most likely due to poor dietary intake, may develop in pediatric patients with classical galactosemia, and folic acid should be supplemented. Folic acid supplementation appears to have a low, but statistically significant, effect on galactose-1-phosphate uridyltransferase enzyme activity, but comprehensive research is needed to clarify whether there is any clinical significance.