Hypophosphatasia Presenting with Pyridoxine-Responsive Seizures, Hypercalcemia, and Pseudotumor Cerebri: Case Report

Hypophosphatasia (HPP) is an inborn error of metabolism characterized by defective bone mineralization caused by a deficiency in alkaline phosphatase (ALP) activity due to mutations in the tissue-nonspecific ALP (TNALP) gene. The clinical expression of the disease is variable. Six forms of HPP are identified according to age at presentation and clinical features. Patients with the infantile form are normal at birth. First symptoms appear within the first 6 months of life. Along with skeletal findings, HPP patients may present with hypercalcemia, seizures, pseudotumor cerebri, and pulmonary insufficiency. Seizures in HPP are refractory to conventional antiepileptic drugs, but are responsive to pyridoxine. Herein, we report a case of HPP who presented with pyridoxine-responsive seizures in the early neonatal period and was found to have hypercalcemia, skeletal demineralization and increased intracranial pressure. Key words: Hypophosphatasia, pyridoxine-responsive seizures, bisphosphonates, alkaline phosphatase, bone resorption, hypercalcemi

Prenatal Diagnosis of Zellweger Syndrome: Case Report

Zellweger syndrome (ZS) (Cerebro-Hepato-Renal syndrome) is a rare autosomal recessive disorder characterized by an absence or marked decrease in peroxisomes, resulting in profound muscular hypotonia and death in the neonatal period. The clinical presentation of ZS is dominated by craniofacial dysmorphic features, neurological abnormalities, hepatomegaly, and chondrodysplasia punctata. Prenatal diagnosis is possible by analysis of dihydroxyacetone-phosphate acyltransferase (DHAPAT) activity, which catalyzes the first step in the biosynthesis of ether-phospholipids, in chorionic villi or amniotic fluid cells. We report the prenatal diagnosis of three pregnancies of a mother who had lost two children previously due to ZS

Prenatal Diagnosis Of Tay-Sachs Disease

OBJECTIVE: To emphasize the efficacy and safety of the prenatal invasive procedures for prenatal diagnosis of Tay-Sachs disease. STUDY DESIGN: In this case series, the results of the prenatal invasive procedures that were performed for diagnosing Tay-Sachs disease in 8 patients between 2000 and 2008 are reported. The samples were obtained by chorionic villus sampling or by cordocentesis. Total hexosaminidase level and the percentage of isoenzyme ß-Hexosaminidase A were measured in fetal samples. RESULTS: There were 8 patients in diagnosed prenatatlly between 2000-2008. Sufficient material for enzyme analysis was obtained without any complications. Total hexosaminidase levels and the percentage of hexosaminidase were in normal limits in all fetal samples. All pregnancies ended up with uneventful term births. CONCLUSION: Tay-Sachs disease can be diagnosed prenatally by measuring hexosaminidase enzyme activity in fetal tissue samples with an acceptable complication rate. Prenatal diagnosis should be offered to families who have affected siblings with Tay-Sachs disease

Prenatal Diagnosis of Sandhoff Disease by Enzyme Analysis of Chorionic Villus Sample

OBJECTIVE AND STUDY DESIGN: The prenatal diagnosis of Sandhoff disease (SD) was performed in 14 fetuses of families by the analysis of chorionic villus sample obtained at 11-14 weeks of gestation. The diagnosis was based on the absence or near-absence of total hexosaminidase activity using fluorogenic synthetic substrate 4-methylumbelliferyl beta-D-glucosaminide. RESULTS: 7 fetuses were found to be affected and the pregnancies were terminated. The remaining seven fetuses were found to be normal. The diagnosis were confirmed after delivery by enzyme analysis of leucocytes isolated from peripheric blood. CONCLUSION: Chorionic villus sampling (CVS) is a safe and accurate method for the first trimester prenatal diagnosis of various genetical disorders if the amount of the chorionic villi taken is sufficient for enzyme analysis and if it is well separated from maternal blood or decidua. Hexosaminidase (Hex) assay using fluorogenic substrate is useful for specific prenatal diagnosis of SD

Vacuoliting Megalencephalic Leukoencephalopathy with Subcortical Cysts, Mapped to Chromosome 22q(tel)

The leukodystrophies form a complex group of orphan genetic disorders that primarily affect myelin, the main constituent of the brain white matter. Among the leukodystrophies of undetermined etiology, a new clinical entity called “vacuoliting megalencephalic leukoencephalopathy” (VL) was recently recognized. VL is characterized by diffuse swelling of the white matter, large subcortical cysts, and megalencephaly with infantile onset. Family studies in several ethnic groups have suggested an autosomal recessive mode of inheritance. We mapped the VL gene to chromosome 22q(tel), within a 3-cM linkage interval between markers D22S1161 and n66c4 (maximum LOD score 10.12 at recombination fraction .0, for marker n66c4; maximum multipoint LOD score 17 for this interval) by genome scan of 13 Turkish families. Linkage analysis under the genetic-heterogeneity hypothesis showed no genetic heterogeneity. No abnormalities were found in three tested candidate genes (fibulin-1 and glutathione S-transferases 1 and 2)

Semiological seizure classification of epileptic seizures in children admitted to video-EEG monitoring unit

WOS: 000378167800001PubMed ID: 27186692We aimed to determine seizure characteristics of pediatric patients with epilepsy, and evaluate if Semiological Seizure Classification (SSC) system is applicable in this cohort. We retrospectively studied 183 patients, aged between 3 months-18 years, admitted to the video-EEG monitoring unit (VEMU). Most patients suffered from intractable epilepsy with comorbidities, and had structural lesions. Seizures were classified based on ictal video-EEG recordings by using SSC system; 157 patients had only one seizure type, 26 had more than one seizure types. Overall 211 seizures and 373 semiologies were analyzed; 114 seizures (54%) had more than one semiological subtype. The most frequent semiology was motor seizures (78%), followed by dialeptic seizures (12%). The most common subtypes were simple motor seizures (49%); tonic seizures constituted (28.4%) of all semiologies. We conclude that SSC system is applicable for children with epilepsy admitted to VEMU; complementary EEG and imaging data are required for evaluation of patients with epilepsy

Long-term effects of vagus nerve stimulation in refractory pediatric epilepsy: A single-center experience

Introduction: Vagus nerve stimulation (VNS) has been used as an adjunctive therapy for both children and adults with refractory epilepsy, over the last two decades. In this study, we aimed to evaluate the long-term effects and tolerability of VNS in the pediatric drug-resistant epilepsy (DRE) and to identify the predictive factors for responsiveness to VNS.Methods: We retrospectively reviewed the medical records of pediatric patients who underwent VNS implantation between 1997 and 2018. Patients with >= 50% reduction of seizure frequency compared with the baseline were defined as "responders". The clinical characteristics of responders and nonresponders were compared.Results: A total of 58 children (male/female: 40/18) with a mean follow-up duration of 5.7 years (3 months to 20 years) were included. The mean age at implantation was 12.4 years (4.5 to 18.5 years). Approximately half (45%) of our patients were responders, including 3 patients (5.8%) who achieved seizure freedom during follow-up. The age of seizure-onset, duration of epilepsy, age at implantation, and etiologies of epilepsy showed no significant difference between responders and nonresponders. Responders were more likely to have focal or multifocal epileptiform discharges (63%) on interictal electroencephalogram (EEG), when compared to nonresponders (36%) (p = .07). Vocal disturbances and paresthesias were the most common side effects, and in two patients, VNS was removed because of local reaction.Conclusion: Our series had a diverse etiological profile and patients with transition to adult care. Long-term follow-up showed that VNS is an effective and well-tolerated treatment modality for refractory childhood onset epilepsy. Age at implantation, duration of epilepsy and underlying etiology are not found to be predictors of responsiveness to VNS. Higher response rates were observed for a subset of patients with focal epileptiform discharges