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Six genes including POMT1, POMT2, POMGNTI, FKRP, Fukutin (FKTN) and LARGE encode proteins involved in the glycosylation of alpha-dystroglycan (alpha-DG). Abnormal glycosylation of alpha-DG is a common finding in Walker-Warburg syndrome (WWS), muscle-eye brain disease (MEB), Fukuyama congenital muscular dystrophy (FCMD), congenital muscular dystrophy types 1C and ID and some forms of autosomal recessive limb-girdle muscular dystrophy (LGMD2I, LGMD2K, LGMD2M), and is associated with mutations in the above genes. FCMD, caused by mutations in Fukutin (FKTN), is most frequent in Japan, but an increasing number of FKTN mutations are being reported outside of Japan. We describe four new patients with FKTN mutations and phenotypes ranging from: severe WWS in a Greek-Croatian patient, to congenital muscular dystrophy and cobblestone lissencephaly resembling MEB-FCMD in two Turkish patients, and limb-girdle muscular dystrophy and no mental retardation in a German patient. Four of the five different FKTN mutations have not been previously described. (C) 2010 Elsevier B.V. All rights reserved.

We prospectively examined the effects of valproic acid on the endocrine system and metabolic variables in epileptic children. Patients with newly diagnosed idiopathic epilepsy were included in the study. Laboratory and clinical variables were assessed before and after 6 and 12 months of treatment. In total, 30 patients (mean age, 8.6 +/- 4.4 years S.D.) were investigated. Body mass index and body mass index standard deviation scores of patients increased significantly during treatment. Although there was no statistical significance regarding fasting glucose, serum insulin, triglyceride, and high-density lipoprotein cholesterol levels and the insulin resistance index, a statistically significant increase in total and low-density lipoprotein cholesterol levels had occurred after 12 months of valproic acid treatment. At the end of the study period, four patients were obese, and six patients were overweight. There was a significant correlation between serum levels of valproic acid and body mass index at month 6 of treatment. There was no significant change in androgen hormone levels during treatment in the prepubertal group. Body mass index and body mass index standard deviation scores increased during the first 6 months of valproic acid treatment. Patients treated with valproic acid should be regularly followed for obesity. (C) 2009 by Elsevier Inc. All rights reserved.

The aim of this study is to evaluate the erythrocyte lipid peroxidation and antioxidant enzyme levels in patients with newly diagnosed idiopathic epilepsy before treatment and in patients treated with valproic acid for idiopathic epilepsy. Twenty-four patients with newly diagnosed idiopathic epilepsy, 24 patients treated with valproic acid for idiopathic epilepsy and 21 healthy children were included in the study. Malondialdehyde as an indicator of lipid peroxidation and antioxidants enzymes including superoxide dismutase and glutathione peroxidase were measured in the erythrocytes. The levels of malondialdehyde were significantly tower and activity of superoxide dismutase was insignificantly higher in patients with newly diagnosed epilepsy. Glutathione peroxidase levels did not differ between the groups. During treatment with valproic acid, lipid peroxidation increased but did not reach pathological levels. There was a positive correlation between superoxide dismutase activity and duration of valproic acid treatment. In conclusion, oxidant-antioxidant status is impaired in patients with primary idiopathic epilepsy and scavenger systems are activated to decrease lipid peroxidation. Valproic acid which is frequently used in childhood epilepsy may modify the balance between oxidant and antioxidant systems. (C) 2009 Elsevier B.V. All rights reserved.

Congenital myasthenic syndromes are a genetically and phenotypically heterogeneous group of hereditary disorders affecting neuromuscular junction. Mutations in the gene encoding choline acetyltransferase cause presynaptic defects. The missense mutation I336T has been identified in Turkish population, and most of the cases carrying this mutation present with exercise-induced fatigability and ptosis. Although apneic attacks occur in these cases during febrile illness in childhood, the number of reported respiratory distress episodes during infancy is scarce. Another important feature of these cases is that response to esterase inhibitors is satisfactory. We present a case of congenital myasthenic syndrome with I336T choline acetyltransferase mutation who presented with numerous attacks of respiratory distress in the infancy period. Interestingly, the patient had myopathic findings on electromyography and diazepam decreased severity of apneic attacks. There was also no improvement with esterase inhibitors.

Acute transverse myelitis is a rare but severe inflammatory demyelinating disorder that usually involves both sensory and motor tracts of the spinal cord [1]. It is characterized by rapid onset of paraplegia or tetraplegia, loss of sensation and sphincter disturbance, and in rare cases it can cause respiratory insufficiency. This disease occurs commonly among adults and rarely in the paediatric population, especially children under 2 years of age [2,3]. The exact pathophysiological mechanisms and trigger factors that result in neural injury are not well understood. However, recent studies point to a variety of humoral and cellular immune derangements that potentially result in neuronal injury and demyelination [4,5]. We report a case of a 9-month-old boy who presented with a 1 month evolving history of progressive generalized weakness.

Mycoplasma pneumoniae is an important pathogen which causes nervous system disorders during or after the course of a respiratory tract infection. The exact pathogenic mechanism which causes neurological disorders still remains unknown. Although meningoencephalitis and acute disseminated encephalomyelitis are common complications, there are few cases of acute transverse myelitis and isolated abducens nerve palsy associated with M. pneumoniae infection in childhood. The association between ocular myasthenia gravis and M. pneumoniae infection has not been described before. Here, we describe five patients with different nervous system complications associated with M. pneumoniae infection and discuss the pathological features of central nervous system involvement.

Background The aim of the study was to investigate safety, efficacy and tolerability of risperidone in comparison with haloperidol in the long-term treatment of autistic disorder. Methods This was an open-label continuation study of the randomized, double-blind, controlled trial of risperidone and haloperidol study for 12 week in autistic children and adolescents. A total of 28 subjects between 8 and 18 ages with autistic disorder were enrolled to the open label phase of the study. Behavioral rating scales (Clinical Global Impression Scale [CGI-I], Ritvo-Freeman Real Life Rating Scale [RF-RLRS]), Aberrant Behavior Checklist [ABC], Turgay DSM-IV Pervasive Developmental Disorder Rating Scale [TPDDRS]) and safety assessment scales (Extrapyramidal Symptoms Rating Scale [ESRS], UKU-Side Effect Rating Scale) were performed at 12, 16, 20 and 24 weeks, following the 12 week double-blind phase. Risperidone and haloperidol treatments were applied with a once daily dosage regimen as 0.01-0.08 mg/kg/day. Results Risperidone led to a significant greater reduction on CGI scale. There was significant improvement on RF-RLRS sensory motor and language subscale and ABC scores in risperidone group. Weight gain was observed more frequently in the haloperidol group at week 24. Conclusions These results demonstrate that risperidone is more efficacious and well tolerated than haloperidol in the long-term maintenance treatment of autistic disorder.

Autosomal dominant spinocerebellar ataxias are neurodegenerative disorders that generally present in adulthood. Due to extreme expansion of the repeat size during spermatogenesis, they can also be observed in childhood. The diagnosis in childhood is very difficult in the absence of family history. Here we describe an 8-year-old girl with spinocerebellar ataxia type 2 who presented with progressive ataxia, cognitive deficits, and dysarthria. A detailed family history exhibited similarly affected cases on the paternal side. Molecular testing for spinocerebellar ataxia type 2 revealed abnormal “cytosineadenine-guanosine” expansion in all affected family members. The number of cytosine-adenine-guanosine repeats in the index case was 70. The mean size of expansion in the relatives of the patient was 42 (39—46). This finding explains the early onset of symptoms in the index case.

Glutaric aciduria type 1 is an inborn error of lysine, hydroxylysine, and tryptophan metabolism caused by deficiency of glutaryl-coenzyme A dehydrogenase. The disease often appears in infancy with an encephalopathic episode that results in acute basal ganglia and white matter degeneration. The neuroimaging findings in glutaric aciduria type I have been well defined. However, the changes in magnetic resonance spectroscopy, a noninvasive tool for identifying the biochemical state of the brain, are scarce in glutaric aciduria type 1. This report presents the magnetic resonance spectroscopy findings in a 19-month-old male with glutaric aciduria type 1. Magnetic resonance spectroscopy of right frontal white matter and right lentiform nuclei revealed decreased N-acetylaspartate/creatine ratio, slightly increased choline/creatine ratio, and increased myoinositol/creatine ratio, compared with the age-matched control patients. We thought that these changes were in accordance with neuroaxonal damage, demyelination, and astrocytosis in these areas. In conclusion, proton magnetic resonance spectroscopy provides a tool for assessing metabolic disturbances and the extent of brain damage noninvasively in glutaric aciduria type 1. (C) 2004 by Elsevier Inc. All rights reserved.

Purpose: Neuronal ceroid lipofuscinoses (NCL) are among the progressive encephalopathies of childhood that are inherited in an autosomal recessive manner. In this study we specifically aimed to investigate any white-matter changes in the carriers (parents) and the healthy siblings of individuals with neuronal ceroid lipofuscinosis disease and whether we may be able to predict the occurrence of any neurological symptoms in healthy children in the future thus enabling early management.Materials and Methods: Since the NCLs are genetically determined diseases, we investigated fifteen individuals in three families that had diseased children of the juvenile type, with brain perfusion SPECT and MRI. Brain perfusion SPECT was performed after administering 222–555 MBq (6–15 mCi) Tc-99m HMPAO intravenously in a dimmed and quiet room. Imaging was performed at least one hour after injection, with a three headed gamma camera equipped with high resolution collimators. A Metz filter (FWHM: 11 mm) was used for processing. Cranial MRI was performed with an imager operating at 1.5 Tesla. Spin-echo TI- and T2-weighted and FLAIR slices were obtained for each individual.Results: In all of the five diseased children we observed pathologic findings both on MRI and Tc-99m HMPAO SPECT. The findings on MRI were mainly features of cerebral and cerebellar atrophy and the observations on Tc-99m HMPAO SPECT were regional perfusion abnormalities. We observed some structural abnormalities on MRI in four of the parents and two of the four healthy siblings. We also noted perfusion abnormalities on Tc-99m HMPAO SPECT in two of the parents and two of the healthy siblings.Conclusion: Because the disease is inherited in an autosomal recessive manner, the parents and the healthy siblings were not supposed to exhibit any demonstrable brain lesions, but the brain perfusion SPECT and MRI examinations clearly revealed multiple lesions in some of the parents and healthy siblings. Detailed neurological examinations of these individuals were normal except for one apparently healthy sibling (EY). Follow-up imaging of these families is being undertaken and further studies are essential in understanding the pathogenesis and genetics of neuronal ceroid-lipofuscinoses.

Marinesco-Sjogren syndrome is an autosomal recessive, multiorgan disorder with cardinal features of cerebellar ataxia, congenital or early childhood cataracts, psychomotor retardation, myopathy, and short stature. Mutations in the SIL1 gene on chromosome 5q31 were demonstrated to cause Marinesco-Sjogren syndrome. We describe two Turkish patients with clinical characteristics of Marinesco-Sj6gren syndrome, but without mutations in SIL1 These two patients also manifested cerebral white matter involvement in cranial imaging, which was previously described in Marinesco-Sjogren syndrome. Marinesco-Sjogren syndrome is genetically heterogeneous, and mutations of SIL1 are often not evident. Consequently, we presume that new genes for Marinesco-Sjogren syndrome await discovery. New genes hold the promise of furthering the mechanistic understanding of the condition, enabling clinically meaningful genetic classification schemes to be designed. (C) 2011 Elsevier Inc. All rights reserved.

To evaluate oxidant status in children after febrile seizures, 61 children were studied: 31 with and 30 without a febrile seizure. Erythrocyte malondialdehyde, glutathione peroxidase, and superoxide dismutase levels were assessed in all patients. Erythrocyte malondialdehyde and glutathione peroxidase levels were significantly higher and superoxide dismutase levels were significantly lower in the febrile seizure group. Febrile seizures may cause significant oxidative stress, and these changes in oxidant status may be a step along the way to cell damage subsequent to febrile seizures. (C) 2009 by Elsevier Inc. All rights reserved.

Although cerebellitis is common in childhood but cerebellitis with cerebellar swelling is rarely reported. Pulsed high dose methylprednisolone treatment is the choice of treatment for cases who have non-progressive symptoms. An 8-year-old girl presented acutely with vertigo, headache, and vomiting. Brain magnetic resonance imaging showed marked bilateral cerebellar swelling with increased signal on T2-weighted imaging. Following treatment with standard dexamethasone dose, the clinical and radiological signs resolved in 1 week. We conclude that standard dexamethasone treatment should be used in mild cases of acute cerebellitis in order to avoid adverse reactions of pulsed high dose methylprednisolone treatment.

The aim of this study was to investigate the effect of family structure and the attitude of mothers on the development of breath-holding spells. The data of the Sociodemographic and Parental Attitude Research Instruments of 30 mothers of children with breathholding spells and of 30 mothers of healthy children were compared. The subjects were also evaluated for iron deficiency anemia and by age-related developmental test. No significant difference was observed between the two groups in the results of the Sociodemographic and Parental Attitude Research Instruments. Iron deficiency anemia was found to be significantly higher in the group of mothers of children with breathholding spells compared with the control group. This study suggests that iron deficiency anemia rather than behavioral or psychosocial problems of mothers plays a role in the development of breath-holding spells. (c) 2006 by Elsevier Inc. All rights reserved.

Most vascular diseases have a tendency to affect both heart and the brain. Intracranial aneurysms are more often found in patients with aorta coarctation than in general population, and aneurysm rupture occurs much earlier in these patients. Here, we report a case of aorta coarctation which was diagnosed with its cerebrovascular complications. Before presenting with cerebrovascular complications, the disease can easily be diagnosed with physical examination and non-invasive radiological investigations like echocardiography or cardiac magnetic resonance imaging.

Summary Neuronal ceroid lipofuscinoses are the most common neurodegenerative childhood onset disorders characterized by autosomal recessive inheritance epileptic seizures progressive psychomotor deterioration visual failure and premature death At least seven subtypes of childhood onset neuronal ceroid lipofuscinoses have been identified of which the late infantile onset forms are genetically the most heterogeneous We present a five year old girl with late infantile neuronal ceroid lipofuscinosis who presented with progressive psychomotor retardation ataxia and epilepsia Palmitoyl protein thioesterase activity was very low and a homozygous mutation was identified in CLN2 gene Turk Arch Ped 2010; 45: 155 7 Key words: CLN2 gene electron microscopy neuronal ceroid lipofuscinosis, Özet Nöronal seroid lipofusinozlar otozomal çekinik kalıtım epileptik nöbetler ilerleyici psikomotor bozulma görme kaybı ve erken ölüm ile belirgin çocukluk çağında en sık görülen nörodejeneratif hastalıklardır Çocukluk çağında nöronal seroid lipofusinozların en az yedi alt tipi tanımlanmış olup bunların içinde geç infantil nöronal seroid lipofusinoz genetik olarak en heterojen tipidir Bu yazıda ilerleyici psikomotor gerilik ataksi ve epilepsi ile getirilen ve geç infantil nöronal seroid lipofusinoz tanısı alan bir olgu sunulmaktadır Palmitoyil protein tiyoesteraz aktivitesi çok düşük olup CLN2 geninde homozigot mutasyon saptanmıştır Türk Ped Arş 2010; 45: 155 7 Anahtar sözcükler: CLN2 geni elektron mikroskopi nöronal seroid lipofusinoz

The aim of this study is to evaluate the clinical, electroencephalographic and polysomnographic features of patients presenting with parasomnias. Cases who were admitted for differentiating parasomnias from epilepsy were included in the study. Clinical features of cases were recorded and routine sleep electroencephalography was obtained from all cases. Cases whose symptoms strongly suggested nocturnal seizure underwent all night video electroencephalography monitoring. Polysomnography was obtained to evaluate the quality of breathing from patients whose symptoms suggested obstructive sleep apnea. Twenty-three patients with no neurological disorder were included in the study. The mean age of the patients was 11.7 ± 2.8 [7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17] years. Twelve patients (52 %) presented with sleep terrors and 11 patients (48 %) presented with sleep walking. All of the patients underwent a routine sleep electroencephalographic study and 15 patients (65 %) whose symptoms strongly suggested nocturnal epilepsy underwent long-term video electroencephalographic evaluation. Ten patients (43 %) underwent polysomnographic study. Three patients (20 %) who underwent long-term video electroencephalographic evaluation were diagnosed to have nocturnal frontal lobe epilepsy and two patients (20 %) who underwent polysomnography had pathological sleep apnea. Eleven patients (48 %) had a psychiatric disorder like major depression, anxiety disorder, hyperactivity disorder and obsessive–compulsive disorder. Childhood cases presenting with parasomnias should be searched for nocturnal epileptic disorders, sleep disordered breathing and psychiatric disorders.

A 12-year-old girl was admitted for the evaluation of epilepsy and psychomotor retardation. She was born at term after an uneventful pregnancy. There was no consanguinity. Developmental milestones were delayed and she had been treated for epilepsy since 3months of age. Shewas walking with support and was able to say a few words like “mama” and “dada.” She had dysmorphologic findings including broad nasal tip, frontal bossing, hypertelorism, tongue hamartomas, notching of the teeth (Fig 1), high arched palate, low set ears, and bilateral preaxial polysyndactyly of bilateral feet with bifid hallux. Deep tendon reflexes were hyperactive. Echocardiography, abdominopelvic ultrasonography, and ophthalmologic examinations were normal. Brain magnetic resonance imaging revealed molar tooth sign and vermian agenesis (Fig 2). A diagnosis of Varadi-Papp syndrome (orofaciodigital syndrome type VI) was made based on her clinical and radiologic findings. Genetic analysis of INPP5 E and TMEM216 genes revealed no mutation.

Friedreich ataksi otozomal resesif geçişli nörodejeneratif bir hastalık olup kalıtsal ataksilerin en sık nedenidir. Hastaların %95’inde kromozom 9q13 üzerinde bulunan FRDA geninin birinci intronunda GAA trinukleotid tekrar artışı mevcuttur. Bu durum demir homeostazında önemli bir role sahip olan frataksin proteininin düzeyinde azalışa yol açar. Friedreich ataksi hastalığının patogenezinden mitokondrilerde demir birikimi ve bunun neden olduğu spesifik mitokondriyal enzim eksiklikleri, oksidatif strese artmış duyarlılık ve serbest radikal aracılı hücre ölümü sorumludur. Günümüzde hastalığın etkin bir tedavisi yoktur, ancak antioksidan tedaviler özellikle kardiyak tutulumda umut vaat etmektedir. Friedreich ataksili olguların erken tanınması ve işlevsel kısıtlılıkların zamanında belirlenmesi rehabilitasyon, semptomatik tedavi ve genetik danışma açısından önemlidir. Bu yazıda homozigot GAA artışına sahip beş hastanın klinik özellikleri sunulmakta ve ilerleyici ataksi ile başvuran hastalarda ayırıcı tanıda Friedreich ataksinin düşünülmesinin gerekliliğini vurgulamaktır. Friedreich ataxia is an autosomal recessive neurodegenerative disease, which is the most common cause of inherited ataxias. About 95% of the patients demonstrate an expansion of a GAA trinucleotide repeat in intron 1 of the FRDA gene on chromosome 9q13. This leads to reduced levels of frataxin which has an important role in iron homeostasis. Friedreich ataxia is the result of accumulation of iron in mitochondria leading to excess production of free radicals, defects in specific mitochondrial enzymes, enhanced sensitivity to oxidative stress, and eventually free- radical mediated cell death. Currently there is no effective therapy for the disease, but antioxidant therapy has shown promise especially in cardiac involvement. Early identification of individuals with Friedreich ataxia and precise characterization of impairments and functional limitations gain importance as symptomatic treatment, rehabilitation and genetic counseling are considered. Here, we present the clinical findings of five cases with Friedreich ataxia who had homozygous GAA trinucleotide expansion and emphasize that Friedreich ataxia should be considered in the differential diagnosis of cases who present with progressive ataxia.

Fibromuscular dysplasia is a rare, idiopathic and nonatheromatous disease. It is rarely encountered as a cause of stroke in children. We report a nine-year-old girl with stroke in whom extensive fibromuscular dysplasia of intracranial vessels was established. She also had familial combined hyperlipidemia as an additional risk factor. This case suggests that additional risk factors like hyperlipidemia in cases with fibromuscular dystrophy may facilitate the occurrence of stroke at early ages.

Centronuclear myopathies (CNM) describe a group of rare muscle diseases typically presenting an abnormal positioning of nuclei in muscle fibers. To date, three genes are known to be associated to a classical CNM phenotype. The X-linked neonatal form (XLCNM) is due to mutations in MTM1 and involves a severe and generalized muscle weakness at birth. The autosomal dominant form results from DNM2 mutations and has been described with early childhood and adult onset (ADCNM). Autosomal recessive centronuclear myopathy (ARCNM) is less characterized and has recently been associated to mutations in BIN1, encoding amphiphysin 2. Here we present the first clinical description of intrafamilal variability in two first-degree cousins with a novel BIN1 stop mutation. In addition to skeletal muscle defects, both patients have mild mental retardation and the more severely affected male also displays abnormal ventilation and cardiac arrhythmia, thus expanding the phenotypic spectrum of BIN1-related CNM to non skeletal muscle defects. We provide an up-to-date review of all previous cases with ARCNM and BIN1 mutations.

Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by near total absence of body fat since birth with predisposition to insulin resistance, diabetes, hypertriglyceridemia, and hepatic steatosis. Three CGL loci, AGPAT2, BSCL2, and CAV1, have been identified previously. Recently, mutations in polymerase I and transcript release factor (PTRF) were reported in five Japanese patients presenting with myopathy and CGL (CGL4). We report novel PTRF mutations and detailed phenotypes of two male and three female patients with CGL4 belonging to two pedigrees of Mexican origin (CGL7100 and CGL178) and one pedigree of Turkish origin (CGL180). All patients had near total loss of body fat and congenital myopathy manifesting as weakness, percussion-induced muscle mounding, and high serum creatine kinase levels. Four of them had hypertriglyceridemia. Three of them had atlantoaxial instability. Two patients belonging to CGL178 pedigree required surgery for pyloric stenosis in the first month of life. None of them had prolonged QT interval on electrocardiography but both siblings belonging to CGL7100 had exercise-induced ventricular arrhythmias. Three of them had mild acanthosis nigricans but had normal glucose tolerance. Two of them had hepatic steatosis. All patients had novel null mutations in PTRF gene. In conclusion, mutations in PTRF result in a novel phenotype that includes generalized lipodystrophy with mild metabolic derangements, myopathy, cardiac arrhythmias, atlantoaxial instability, and pyloric stenosis. It is unclear how mutations in PTRF, which plays an essential role in formation of caveolae, affect a wide variety of tissues resulting in a variable phenotype. (C) 2010 Wiley-Liss, Inc.

Megalencephalic leukoencephalopathy with subcortical cysts is a rare leukodystrophy that is characterized by macrocephaly and a slowly progressive clinical course. It is one of the most commonly reported leukoencephalopathies in Turkey. Mutations in the MLC1 gene are the main cause of the disease. We report two patients with megalencephalic leukoencephalopathy with subcortical cysts with confirmed mutations in the MLC1 gene. The mutation in the second patient was novel. We also review identified mutations in the Turkish population.

Dentatorubral pallidoluysian atrophy is a neurodegenerative disease that generally presents in adulthood. Although rare, it can be observed in childhood due to extreme expansion of the triplet repeat size during spermatogenesis. The diagnosis in childhood is very difficult in the absence of family history. Here we describe a 12-year-old girl with dentatorubral pallidoluysian atrophy who presented with progressive myoclonic epilepsy and ataxia. Family history exhibited similarly affected cases on the paternal side. Molecular testing for dentatorubral pallidoluysian atrophy revealed abnormal "cytosine-adenine-guanosine" expansion in the atrophin-1 gene.

The aim of this study is to evaluate the carotid artery intima media thickness and serum lipids in pediatric patients with epilepsy treated with valproic acid. The study included 44 pediatric epileptic and 40 healthy children. Intima media thickness of left common carotid artery and fasting lipid profile (total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol) were assessed. Although we did not observe any differences regarding serum lipid profiles, intima media thickness of common carotid artery was significantly higher in epileptic patients treated with valproic acid. We suggest that this increase in intima media thickness of common carotid artery may be due to epilepsy and/or valproic acid treatment. (C) 2008 Elsevier B.V. All rights reserved.

Spinocerebellar ataxia type 2 is a neurodegenerative disease caused by a CAG repeat expansion in the ataxin-2 gene. Gain-of-toxic effects caused by expanded polyglutamine tracts are important for the disease pathogenesis and there is an inverse relationship between the number of CAG repeats and the age of onset and clinical severity. Previously, we reported an extended Turkish family with spinocerebellar ataxia type 2 with several affected members in three generations. Two sisters in this generation showed an earlier age of onset (5 and 7 years, respectively) than their father (30 years). In this paper, we present a further interesting finding regarding the disease onset and manifestation in the two sisters. Interestingly, the age of onset was delayed and the clinical severity of the disease was milder in the child who had more CAG repeats (84 vs. 70). This finding suggests that there are other factors contributing to the age of onset and clinical severity in spinocerebellar ataxia type 2 other than the increased CAG repeat.

Nonketotic hyperglycinemia is an autosomal recessive disorder of glycine metabolism. Patients generally present in the neonatal period with lethargy, feeding difficulty, hypotonia, apnea, poorly controlled convulsions, and coma. Myoclonic seizures and burst suppression pattern on electroencephalography are major findings of disease, but development of hydrocephalus is not an expected finding. The present case is that of an infant with acquired hydrocephalus, psychomotor retardation, and myoclonic seizures in whom the final diagnosis was nonketotic hyperglycinemia. (C) 2009 by Elsevier Inc. All rights reserved.

It has long been known that the anti-epileptic, valproate (VPA), which is used widely in the treatments of generalized and focal seizures, may cause subclinical alterations in both intrinsic and extrinsic coagulation pathways. These changes include thrombocyte dysfunction, thrombocytopenia, von Willebrand disease type I, deficiency of vitamin K-dependent coagulation factors 11, VII, IX, and X and reduction in serum fibrinogen, protein C and protein S concentrations. In addition macrocytosis, erythrocytopenia, neutropenia, reduction in hemoglobin and hematocrit counts and bone marrow suppression are reported to accompany VPA treatment. The incidence of these disturbances is higher in children than in adults.(1) These side-effects of VPA may either be dose related, or idiosyncratic, but life-threatening hemorrhage in such cases is rare. The aforementioned hernatological disturbances are generally identified following chronic VPA treatment and when VPA blood concentrations are >100 mu/mL;(2) they can be recurring, temporary or permanent.

An 8-month-old girl and a 20-month-old boy who presented with motor and developmental delay and long-standing fever are presented. The patients were diagnosed as Angelman syndrome with fluorescence in situ hybridization (FISH) analysis. Despite extensive clinical and laboratory examinations, no inflammatory or infectious origin for the fever was found. It was considered that the long-standing fever observed in these cases was due to hypothalamic dysfunction for thermoregulation.

Multiple sulfatase deficiency (MSD) is an inherited lysosomal storage disease that affects post-translational activation of all of the sulfatases. Since biochemical and clinical findings are variable, the diagnosis is difficult in most of the cases. Missense, nonsense, microdeletion and splicing mutations in SUMF1 gene were found in all of the MSD patients analyzed. Here, we present clinical findings of two consanguineous patients with multiple sulfatase deficiency. They were found to be homozygous for a novel missense mutation c.739G > C causing a p.G247R amino acid substitution in the SUMF1 protein. (c) 2007 Elsevier B.V. All rights reserved.

The pathological nature of Leigh syndrome is highly variable and depends on the underlying mitochondrial or nuclear genome defect. Mitochondrial m.8993T>G and m.8993T>C mutations are responsible for both NARP (neurogenic weakness, ataxia and retinitis pigmentosa) and Leigh syndrome depending on the amount of mutant mtDNA. The clinical findings of Leigh syndrome caused by the m.8993T>C mutation are less severe than those associated with the m.8993T>G mutation, and ragged red fibers, oligoclonal bands in cerebrospinal fluid, and additional deficiencies of respiratory enzyme complexes are usually not found. This report presents a two year old girl with Leigh syndrome caused by a m.8993T>C mutation. Interestingly she had ragged red fibers in muscle tissue, oligoclonal bands in CSF and focal deficient histochemical staining for complexes I and IV. (C) 2008 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

The kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VI) (OMIM 225400) is an inherited connective tissue disorder characterized by hypotonia and kyphoscoliosis at birth, joint hypermobility, and skin hyperelasticity and fragility. Biochemically, it is characterized by a deficiency of collagen lysyl hydroxylase (EC 1.14.11.4) due to mutations in PLOD1. This deficiency results in underhydroxylation of collagen lysyl residues and, hence, an abnormal pattern of lysyl pyridinoline (LP) and hydroxylysyl pyridinoline (HP) crosslinks excreted in the urine. Because of hypotonia and delay in gross motor development, a neuromuscular disease is usually suspected, and in most cases the diagnosis is considered only very late, after performing an invasive neuromuscular work-up with normal results. We report a 12-month-old boy with kyphoscoliosis and delayed gross motor development, in whom the differential diagnosis of kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VI) was initially suspected and successively confirmed by the abnormal urinary ratio of total pyridinolines (LP to HP), and by mutation analysis. We advocate the analysis of urinary pyridinolines in all infants with severe hypotonia which is highly specific and sensitive, quick and inexpensive.

The aim of the study was to compare safety, efficacy and tolerability of risperidone with haloperidol in the treatment of Autistic Disorder (AD). Method This study was designed as a double-blind, prospective, for a 12-week period. A total of 30 subjects, between the ages of 8 and 18 with AD based on DSM IV criteria, were included in the study. Behavioral Rating Scales were performed by the investigators and the parents. Safety assessment included vital signs, electrocardiogram, electroencephalogram, adverse events, laboratory tests, extrapyramidal symptoms and the side effects. Both treatments were applied in a once daily dosage regimen of 0.01-0.08 mg/kg/day. Results The reduction from baseline in Ritvo-Freeman Real Life Rating Scale (RF-RLRS), sensory motor (subscale I) and language (subscale V) scores were significant in risperidone group (P < 0.05). Compared to haloperidol, risperidone led to a significantly greater reduction in the Aberrant Behavior Checklist (ABC) and Turgay DSM-IV Pervasive Developmental Disorder (PDD) scale scores (P < 0.05 and P < 0.01). There was a greater increase of prolactin in the risperidone group, while alanine amino transferase (ALT) had further increased in the haloperidol group. Sensory motor behaviors (subscale I) and language at the end of the 12th week, RF-RLRS sensory motor and language subscale scores decreased in the risperidone group further than the other group (P < 0.05). Conclusions Risperidone was found to be more effective than haloperidol in the treatment of behavioral symptoms, impulsivity, language skills, and impaired social relations in children with AD. These results demonstrated that both drugs were safe and well tolerated in the treatment of AD.

A patient with isolated 3-methylcrotonyl-CoA carboxylase (MCC) deficiency with an unusual clinical presentation is described. The patient presented with clusters of seizures with two or three months disease free interval in the first year of life which then evolved into attacks of status epilepticus after the age of 12 months. MCC deficiency was suspected because of elevated C5-OH-carnitine in tandem mass spectrometry and elevated 3-hydroxy-isovaleric acid in urine organic acid analysis. Deficiency of MCC was confirmed in cultured fibroblasts and mutation analysis revealed a novel mutation in MCCB, p.S39F. Attacks of status epilepticus as a predominant symptom have not been described before in isolated MCC deficiency. (c) 2007 Elsevier B.V. All rights reserved.

Background: The majority of previous studies on headache in children and adolescents have focused mainly on migraine. There is a paucity of population-based studies investigating the prevalence of tension-type headache (TTH). The objectives of the present study were to estimate the prevalence of migraine and TTH in adolescents using the 2004 International Headache Society (IHS) criteria and to determine the sociodemographic and clinical differences between the migraine and TTH. Methods: Stratified group sampling was used in the present analytic, school-based, cross-sectional study. From the city of Izmir, 2384 students aged 14–18 years were invited to complete a questionnaire. Results: Migraine was found to be more common than TTH (21.3% vs 5.1%). The prevalence increased considerably to 29.9 and 15%, respectively, when the criteria defining the number and duration of headaches were excluded. All types of headaches were more frequent in female subjects but no significant difference was found in gender between the headache groups (P= 0.073). Headache in temples, number of siblings (more than one sibling), mother’s and father’s education (at least high school graduation) were more commonly seen in students with TTH. Absenteeism rate due to the headache was found to be higher in the migraine group than in the TTH group (P= 0.000). Conclusions: Migraine and TTH were found to be common types of headaches in adolescents. It was thought that, with the use of modified IHS criteria, the number of undiagnosed patients with headache will decrease.

Prothrombin G20210A mutation is an important prothrombotic condition for venous thrombosis. Recently, some studies have also considered it to be a risk factor for arterial ischemic stroke in children. A 10-year-old boy with basilar artery thrombosis who was heterozygous for prothrombin G20210A mutation is described. In concordance with the previous literature, the present case suggests that prothrombin G20210A mutation may be a risk factor for arterial ischemic stroke in childhood.

Cerebral volumetric measurements based on magnetic resonance imaging have been established as advanced morphometric techniques with anatomic and clinical utility in adults and children with epilepsy. This study investigated the cerebral and hippocampal volumes in children with idiopathic partial epilepsy to detect the factors correlated with volume reduction. Magnetic resonance imaging volumetric measurements were performed of the total cerebral and hippocampal formation volumes in 30 patients with idiopathic partial epilepsy between 3 to 18 years old. The cerebral and the total, right, and left hippocampal volumes of the study and control patients were detected using volumetric magnetic resonance imaging, and the volumes were compared between the 2 groups. In study patients, the correlation between volumetric findings and seizure characteristics was evaluated. The results suggested that children with idiopathic partial epilepsy had significant hippocampal volume reduction that was not influenced by the age of onset and the duration of epilepsy.

Walker-Warburg syndrome (WWS), the most severe alpha-dystroglycanopathy, is characterized by brain and eye anomalies, and congenital muscular dystrophy (CMD). So far at least four genes (POMT1, POMT2, Fukutin, and FKRP gene) have been implicated in WWS, accounting for about 30% of all cases. We report a male patient with WWS resulting from a homozygous nonsense mutation (R514X) in the POMT1 gene. The patient had congenital hydrocephalus which was detected at 29 weeks of gestation. A brain MRI obtained after birth revealed type II lissencephaly, hydrocephalus, and pontocerebellar hypoplasia. The case also exhibited severe ocular malformations and muscular hypotonia due to CMD. (c) 2006 Published by Elsevier Ltd. on behalf of European Paediatric Neurology Society.

The aim of this study is to determine the frequency of changes in biochemical markers of bone metabolism in children who are receiving valproic acid, carbamazepine, and oxcarbazepine. Thirty healthy children and 68 children with idiopathic epilepsy treated with either carbamazepine (n = 23), valproic acid (n = 31), or oxcarbazepine (n = 14) for more than 1 year were enrolled into the study. Blood samples were obtained in order to determine biochemical parameters (calcium, phosphorus, alkaline phosphates, parathormone, and 25-hydroxyvitamin D). Bone mineral density was measured with the dual-energy x-ray absorptiometry method. There were no significant differences in the serum concentrations of calcium, phosphorus, aspartate aminotransferase, alanine aminotransferase, and albumin levels between the four groups. However, serum alkaline phosphatase concentrations were higher in the patient group as compared with the control subjects. In patients receiving antiepileptic drugs, bone mineral density values were significantly lower than the healthy control group. In conclusion, long-term antiepileptic drug treatment either with valproic acid, carbamazepine, or with oxcarbazepine which has unknown effects on skeletal mineralization, induces a state of decreased bone mineral density. (c) 2006 by Elsevier Inc. All rights reserved.