CAMLG-CDG: a novel congenital disorder of glycosylation linked to defective membrane trafficking.

The transmembrane domain recognition complex (TRC) pathway is required for the insertion of C-terminal tail-anchored (TA) proteins into the lipid bilayer of specific intracellular organelles such as the endoplasmic reticulum (ER) membrane. In order to facilitate correct insertion, the recognition complex (consisting of BAG6, GET4 and UBL4A) must first bind to TA proteins and then to GET3 (TRC40, ASNA1), which chaperones the protein to the ER membrane. Subsequently, GET1 (WRB) and CAML form a receptor that enables integration of the TA protein within the lipid bilayer. We report an individual with the homozygous c.633 + 4A>G splice variant in CAMLG, encoding CAML. This variant leads to aberrant splicing and lack of functional protein in patient-derived fibroblasts. The patient displays a predominantly neurological phenotype with psychomotor disability, hypotonia, epilepsy and structural brain abnormalities. Biochemically, a combined O-linked and type II N-linked glycosylation defect was found. Mislocalization of syntaxin-5 in patient fibroblasts and in siCAMLG deleted Hela cells confirms this as a consistent cellular marker of TRC dysfunction. Interestingly, the level of the v-SNARE Bet1L is also drastically reduced in both of these models, indicating a fundamental role of the TRC complex in the assembly of Golgi SNARE complexes. It also points towards a possible mechanism behind the hyposialylation of N and O-glycans. This is the first reported patient with pathogenic variants in CAMLG. CAMLG-CDG is the third disorder, after GET4 and GET3 deficiencies, caused by pathogenic variants in a member of the TRC pathway, further expanding this novel group of disorders.

Coats plus syndrome: a rare cause of severe gastrointestinal tract bleeding in children - a case report.

BACKGROUND: Coats plus syndrome, cerebroretinal microangiopathy with calcifications and cysts, is a rare disease with autosomal recessive pattern occurring due to a mutation in CTC1, encoding conserved telomere maintenance component 1, gene. Besides retinal involvement, abnormalities in brain and osteopenia, serious life-threatening bleeding in gastrointestinal tract and portal hypertension can be observed. CASE PRESENTATION: A 6-year-old girl with Coats plus syndrome presented to the pediatric emergency department with vomiting blood and blood in stool. An upper and lower gastrointestinal endoscopy revealed esophageal varices and vascular telangiectasia in the pyloric antrum, duodenum, and colon. She received palliative care and the bleeding was stopped after receiving intravenous octreotide. She then was followed in the pediatric gastroenterology, neurology, and ophthalmology clinics. She was later hospitalized and admitted to the intensive care unit as she continued to have intermittent gastrointestinal system bleeding. She eventually died due to severe gastrointestinal system bleeding. CONCLUSIONS: Coats plus syndrome can lead to life-threatening gastrointestinal bleeding and portal hypertension. As Coats plus syndrome is quite rare, there is little published data on this syndrome. This report presents a case of Coats plus syndrome as a rare cause of gastrointestinal bleeding and portal hypertension.

Guillain-Barré syndrome in children: subtypes and outcome.

OBJECTIVE: This study reviews the clinical features, subtypes, and outcomes of childhood Guillain-Barré syndrome (GBS). METHODS: Fifty-four children who attended a tertiary care training and research hospital in Turkey were enrolled in the study. RESULTS: The mean age was 6.5 ± 4.2 years and 32 patients (59.5%) were male. The most common subtype of GBS was acute inflammatory demyelinating polyneuropathy (AIDP), which was seen in 27 patients (50%). Having antecedent history, especially upper respiratory tract infection was significantly more common in AIDP (P = 0.028). Sensorial symptoms were significantly more frequent in axonal type GBS (P = 0.001). When we compare the demyelinating and axonal forms, all of the groups had favorable outcome. CONCLUSION: The diagnosis of pediatric GBS can be delayed because of its variable presentation. Early admission to hospital and early treatment are important for decreasing the need for respiratory support and improving the outcome.

A Multinational Survey on Actual Diagnostics and Treatment of Subacute Sclerosing Panencephalitis.

Subacute sclerosing panencephalitis (SSPE) is a chronic infection of the central nervous system caused by the measles virus (MV). Its prevalence remains high in resource poor countries and is likely to increase in the Northern Europe as vaccination rates decrease. Clinical knowledge of this devastating condition, however, is limited. We therefore conducted this multinational survey summarizing experience obtained from more than 500 patients treated by 24 physicians in seven countries. SSPE should be considered in all patients presenting with otherwise unexplained acquired neurological symptoms. In most patients, the diagnosis will be established by the combination of typical clinical symptoms (characteristic repetitive myoclonic jerks), a strong intrathecal synthesis of antibodies to MV and typical electroencephalogram findings (Radermecker complexes). Whereas the therapeutic use of different antiviral (amantadine, ribavirin) and immunomodulatory drugs (isoprinosine, interferons) and of immunoglobulins has been reported repeatedly, optimum application regimen of these drugs has not been established. This is partly due to the absence of common diagnostic and clinical standards focusing on neurological and psychosocial aspects. Carbamazepine, levetiracetam, and clobazam are the drugs most frequently used to control myoclonic jerks. We have established a consensus on essential laboratory and clinical parameters that should facilitate collaborative studies. Those are urgently needed to improve outcome.

Pediatric syncope: is detailed medical history the key point for differential diagnosis?

Syncope is a transient loss of consciousness as a result of global cerebral hypoperfusion. It is generally benign but may be a sign of pathology. The purpose of this study was to analyze the frequency of syncope due to cardiac, neurocardiogenic, neurologic, situational, psychiatric, and other causes and make a differential diagnosis of syncope types according to detailed medical history and further investigations. We examined prospectively 268 children presented to pediatric polyclinics as well as cardiology and neurology departments (age range, 1-18 years) with a primary complaint of syncope for the study. Cardiac syncope was diagnosed in 12 patients, neurocardiogenic syncope in 232, neurologic syncope in 9, psychiatric syncope in 9, situational in 4, and benign paroxysmal positional vertigo in 2. The neurologic syncope group consists of patients diagnosed with epilepsy after evaluation. Eight patients in the cardiac syncope group were found to have diseases such as long QT syndrome, and the remaining patients had hypertrophic cardiomyopathy, atrioventricular nodal reentry tachycardia, ventricular tachycardia, and a second-degree heart block that can cause sudden death. In conclusion, syncope is a common problem in childhood that requires hospitalization. Because it may be the first finding of an underlying malignant cardiac or neurologic disease, clinicians must be very careful during medical evaluation. An electrocardiogram and a medical history including the details of the event, chronic diseases, and familial diseases are among the most important steps for the right diagnosis and prognosis. Instead of a routine procedure, further diagnostic workup should be directed according to medical history for high yield. Convulsive movements may be defined in all types of syncope related with cerebral hypoxia, and this may lead to a misdiagnosis of seizure by the clinician.

A case of Bartonellosis mimicking systemic lupus erythematosus.

BACKGROUND AND AIM: Cat-scratch disease (CSD) is a systemic bacterial infection caused by Bartonella henselae. The disease is typically characterized by regional lymphadenopathy developing after scratches from domestic or feral cats. Rarely, systemic involvement may be observed. The co-occurrence with glomerulonephritis and positive antinuclear antibody (ANA) tests have been reported before. In these cases, the disease can be misdiagnosed as systemic lupus erythematosus. Ocular involvement occurs in 5%-10% of the cases with CSD, and neuroretinitis is among the common manifestations. Administration of corticosteroids (CSs) in addition to antibiotics has been shown to improve prognosis in neuroretinitis cases. However, the optimal dose and duration, remain ill-defined. CASE REPORT: In this article, we present an 11-year-old girl with CSD and neuroretinitis with a positive ANA test and hematuria, who benefited from high-dose methyl-prednisolone and antibiotics. CONCLUSION: Further research is warranted in order to determine the dose and duration of CSs in the treatment of Bartonella neuroretinitis.

Assessment of bone density in children with cerebral palsy by areal bone mineral density measurement.

The aim of this cross-sectional study was to investigate the frequency of decreased areal bone mineral density (aBMD) among patients with cerebral palsy (CP), as estimated by using various aBMD Z-score adjustment methods. In addition, this study examined factors related to decreased aBMD scores. One hundred and two children between the ages of 3.2 and 17.8 years were examined. In patients with severe CP, the incidences of decreased aBMD according to various adjusting methods based on decimal age, bone age, height age, and height-for-age Z-score (HAZ) were 79.5%, 69.5%, 51.9%, and 38.3%, respectively. Abnormal levels of calcium, phosphorus, alkaline phosphatase, parathyroid hormone, or anticonvulsant were not predictive for a decreased aBMD. Mean aBMD Z-scores were significantly lower in all aBMD Z-score adjustment methods in patients with severe CP compared to patients with mild-to-moderate CP, except for the adjustment method based on HAZ.

A Case of Smith-Lemli-Opitz Syndrome Diagnosed with Hypertrophic Pyloric Stenosis.

Smith-Lemli-Opitz syndrome (SLOS) is caused by a deficiency in the enzyme 7-dehydrocholesterol reductase (DHCR7) that results in an abnormality in cholesterol metabolism. SLOS is inherited as an autosomal recessive genetic disorder. In this case, we describe a 34-day-old patient with postnatal progressive projectile vomiting, diagnosed with hypertrophic pyloric stenosis, who was suspected to have SLOS during treatment clinical and biochemical profile. A 34-day-old patient with progressively worsening vomiting and abdominal distention, diagnosed as hypertrophic pyloric stenosis, was operated by pediatric surgery department. After operation, the patient required pediatric intensive care unit admission due to respiratory distress, anemia, hypoalbuminemia, and generalized edema. Physical examination of our patient revealed dysmorphic facial features, finger anomalies, sacral dimple, and ambiguous genitalia, with chromosomal determination as XY. Molecular genetic testing was performed, and mutations in the DHCR7 gene of homozygous c.1342G>A/p.Glu448Lys (rs80338864) were detected. Infants with progressive projectile vomiting, feeding problems, and multiple anomalies with dysmorphic facial anomalies may be suspected to have SLOS and their families should be advised to have genetic testing and genetic counseling.

Neuromotor Development Evaluation of Preterm Babies Less than 34 Weeks of Gestation with Bayley III at 18-24 Months.

OBJECTIVES: To assess and evaluate the risk factors affecting the neuromotor development of preterm babies at corrected age 18 to 24 months. METHODS: Preterm babies ≤ 34 weeks of gestational age (GA) who were born in our hospital between 2011 and 2014 were prospectively included in the study. Prenatal, perinatal, and postnatal features of the babies were recorded. Bayley Scales of Infants and Toddler Development, Third Edition (Bayley-III), was applied at corrected age 18 to 24 months. RESULTS: All data of 96 babies were obtained during the study, mean birth weight was 1542 ± 518 g, and mean corrected age was 20.9 ± 4.7 months. Cerebral palsy was found in 11 babies (11.5%). According to Bayley III scores, 13.5% cognitive delay, 19.8% language delay, and 33.3% motor delay rations were detected. A positive correlation was found between GA and motor composite scores (p = 0.011). The mean motor composite score was lower in babies with the Apgar score less than 7 at 1st and 5th minutes (p = 0.007 and p = 0.003) and applied resuscitation in the delivery room (p = 0.033). The mean language composite score was found to be higher in babies with antenatal steroid administration (p = 0.003). A negative correlation was found between the motor composite score and the oxygen treatment time and mechanical ventilation support time (p = 0.001 and p = 0.007). CONCLUSION: In preterm babies less than 34 weeks, the birth weight, GA, Apgar score, oxygen treatment time, mechanical ventilation support time, and resuscitation in a delivery room were determined to affect the Bayley III motor score. Language development was found better in babies with antenatal steroid administration.

Midterm Neuromotor Development Results of Preterm Babies less than 34 Weeks Gestational Age.

OBJECTIVES: This study aimed to evaluate the neuromotor development of premature babies and to determine the risk factors affecting neuromotor development in the middle time (3 years). METHODS: All babies with ≤34 weeks gestational age and born between 2011-2014 and hospitalized in our neonatal clinic were included in this study. Prenatal, perinatal and postnatal features of the babies were recorded. Consent was obtained from the families who had an outpatient follow-up and agreed to participate in this study. Neurological examination and Denver II Developmental Screening Test (DDST-II) were applied to babies and their results were recorded. Factors affecting neurodevelopment were evaluated. RESULTS: Complete data for 96 of the study infant were obtained. Fifty (52.1%) of the cases were female. The mean birth weight was 1542±518 grams. The mean corrected age was 20.9±10.7 months at the time of the examination. It was found cerebral palsy in 11 babies (11.5%) with the neurological examination and developmental retardation in 15 babies (15.6%) with DDST-II. Low birth weight, a gestational period of 25-26 weeks, Apgar score at 5th minute <7 were found to be the main risk factors for cerebral palsy and abnormal DDST-II result (p<0.05). In babies with abnormal neurological examination, the frequency of bronchopulmonary dysplasia, sepsis and intraventricular hemorrhage were found to be high (p<0.05), and in babies with abnormal DDST-II results the frequency of respiratory distress syndrome, bronchopulmonary dysplasia and sepsis were found to be high (p<0.05). CONCLUSION: In our study, abnormal neurological examination rate was found 11.5% in preterm infants with gestational age ≤34 weeks, and the rate of abnormal DDST-II was found 15.6%. The main factors affecting neuromotor development were gestational week, birth weight and 5th minute Apgar score. The frequency of bronchopulmonary dysplasia, sepsis and intraventricular hemorrhage in babies with abnormal neurological examination, and the frequency of respiratory distress, bronchopulmonary dysplasia and sepsis were found to be high in babies with abnormal DDST-II.

Management of central diabetes insipidus with oral desmopressin in a patient with ectrodactyly and cleft lip/palate (ECP) syndrome.

We present a female infant with facial abnormalities such as bilateral cleft lip and palate, ectrodactyly and central diabetes insipidus. She had a history of recurrent hypernatremic attacks and she was treated successfully with oral desmopressin. As an alternative to the nasal route, long-term management was achieved using oral route and she had a favorable growth and development during infancy.

Acute hemorrhagic pancreatitis due to the use of valproic acid in a child.

Acute pancreatitis is rarely seen in children, and it is often drug induced. Valproic acid (VPA) is one of the most widely used anticonvulsants for children all over the world. We present 11-year-old boy developing pancreatitis after 6 months of therapy with VPA. The symptoms of pancreatitis subsided within 2 weeks after discontinuation of VPA. It seems that the prognosis of VPA-associated acute pancreatitis depends on early diagnosis, timely withdrawal of the offending agent and the treatment.

Retrospective analysis of children with myelin oligodendrocyte glycoprotein antibody-related disorders.

BACKGROUND: Knowledge has been expanding on myelin oligodendrocyte glycoprotein (MOG) antibody-associated central nervous system disorders. We delineate the clinical and paraclinical findings and outcome of our pediatric patients with MOG antibody seropositive disease. METHODS: We retrospectively analyzed the clinical presentation, cerebrospinal fluid findings, magnetic resonance imaging (MRI) studies, course and outcome of children seropositive for anti-MOG IgG. RESULTS: Total 20 children with neurological symptoms and serum anti-MOG IgG were identified from six centers in Turkey. Median age at onset was 9 years (mean 8.8 ±â€¯5.0 years, range: 1.5-16.5 years). Final diagnoses were acute disseminated encephalomyelitis (ADEM) (n = 5), ADEM + optic neuritis (n = 4), neuromyelitis optica spectrum disorder (NMOSD) (n = 3), myelitis (n = 2), relapsing optic neuritis (n = 2), multiphasic DEM (n = 3), and unclassified relapsing demyelinating disease (n = 1). Seven/20 (35%) children experienced a single episode while 13/20 (65%) had a least one relapse during follow-up. On MRI, subcortical white matter, brainstem, and corpus callosum were preferentially involved regions. Full recovery was observed in 15/20 (75%) children. CONCLUSION: MOG autoimmunity in children has a wide clinical spectrum, tendency to relapse, and a favourable outcome compared with other relapsing demyelinating diseases.

Cyclic vomiting with generalized epileptiform discharges responsive to topiramate therapy.

Cyclic vomiting syndrome is a disorder characterized by recurrent attacks of vomiting and intervals of normal health between vomiting episodes averaging 2-4 weeks. It has been described by a variety of names such as abdominal migraine, abdominal epilepsy, and periodic syndrome but now has been classified in the subgroup of childhood periodic syndromes that are commonly precursors of migraine. Topiramate is an antiepileptic drug used both in the treatment of epilepsy and in migraine prophylaxis. This report presents a child with cyclic vomiting syndrome with generalized epileptiform discharges who responded to topiramate therapy. The common features of epilepsy, migraine, and cyclic vomiting syndrome are discussed.

Outcomes of Botulinum Toxin Type A Injection Followed by Rehabilitation in Cases of Cerebral Palsy With Upper Extremity Involvement.

We evaluated the efficiency of botulinum toxin type A injection followed by a rehabilitation program including individual therapy, group therapy, and occupational therapy in cases of cerebral palsy with upper extremity involvement. A total of 29 injections were performed on 25 patients, and the patients were placed on rehabilitation program. At 3-month and 6-month assessments, there was a significant improvement in lateral grip strength, 9 Hole Peg test, Upper Limb Physician's Rating Scale and pediatric functional independence measure total scores. There were significant decreases in active range of motion in elbow extension, supination, and wrist extension, and Modified Ashworth Scale in elbow flexion, elbow pronation, and wrist flexion at 6-week, 3-month, and 6-month assessments. Combination of group therapy with traditional therapy methods after injection is effective in cases of cerebral palsy with upper extremity involvement.

Microsomal triglyceride transfer protein gene mutations in Turkish children: A novel mutation and clinical follow up.

Abetalipoproteinemia (ABL; OMIM 200100) is a rare autosomal recessive disease that affects the absorption of dietary fats and fat soluble vitamins. Here, we describe the clinical and genetic characteristics of three patients with ABL. Two patients (patients 1 and 2) who were carriers of the c.398-399delAA mutation (previously known mutation) had developmental delay and hepatic steatosis developed at the age of five in patient 1. Patient 3 was the carrier of a novel mutation (g.10886-10902delAAGgtaagtttgtgttg in intron 3 and c.506A>T exon 5) in microsomal triglyceride transfer protein (MTP) gene and had hepatic steatosis.

Serological follow-up in juvenile myasthenia: clinical and acetylcholine receptor antibody status of patients followed for at least 2 years.

Thirty cases of juvenile myasthenia with at least 2 years' follow-up and one measurement of acetylcholine receptor antibody titer were evaluated. Symptoms were initially ocular in 15 (50%) cases; only one developed generalized disease and others remained ocular in 2-24 years' follow-up. Antibodies to acetylcholine receptor (AchRAb) were absent in 12/30 (40%) of all patients initially, but became positive in 5/28 (18%) on further testing in 1-5 years. Spontaneous remission was observed in 6 cases (20%) of whom one became seropositive, and late relapses after 5-11 years' remission were observed in 3 patients with ocular myasthenia, of whom only one developed AchRAbs. Our results show ocular JM has an exceptional tendency to remain confined to these muscles, and delaying the classification of the disease as AchRAb-negative for a few years and repeating serological tests is advisable in the follow-up.

Lymphocyte subsets, TNF alpha and interleukin-4 levels in treated and untreated subacute sclerosing panencephalitis patients.

Immunologic studies in relation to clinical status might help to understand the pathogenesis of subacute sclerosing panencephalitis (SSPE) and the effect of treatment. We measured lymphocyte subsets and intracellular TNFalpha and interleukin-4 levels in peripheral blood in SSPE patients. Patients had elevated percentages of CD8+ cells compared to age-matched control children. Rapidly progressive course was associated with increased CD4+ cells. Treatment with interferons and inosiplex altered the percentage of CD3+, CD4+ and CD19+ cells. TNFalpha and interleukin-4 levels had no correlation with course or treatment. The proportions of lymphocyte subsets appear to have a role in the evolution or manifestations of SSPE, if not in the pathogenesis.

Childhood case of progressive multifocal leukoencephalopathy with improved clinical outcome.

A 6-year-old boy who had been in remission from acute lymphoblastic leukemia for 2.5 years presented with seizures, hemiparesis, visual loss, and white- and gray-matter lesions on cranial magnetic resonance imaging. The diagnosis of progressive multifocal leukoencephalopathy was established on the detection of JC virus DNA by polymerase chain reaction in brain tissue. The patient was administered several anticonvulsants, amantadine, acyclovir, and ganciclovir. He showed partial recovery. This case illustrates the possibility of long-term survival in progressive multifocal leukoencephalopathy with normal immunologic parameters.

Severe lethal spinal muscular atrophy variant with arthrogryposis.

Spinal muscular atrophies are a clinically and genetically heterogeneous group of disorders. Atypical forms of the disease have also been described, including those with associated sensory deficits, hearing loss, cerebellar hypoplasia, congenital heart defects, arthrogryposis, and bone fractures at birth. The patient described here is a male infant, born to a 30-year-old mother at 34 weeks of gestation complicated with polyhydramnios. The first son of consanguineous parents had died with the same clinical features. The patient required ventilatory support because of respiratory failure after the birth and died on day 13. His physical examination revealed profound generalized hypotonia, absence of deep tendon and neonatal reflexes, dysmorphic facies, arthrogryposis, clinodactyly, and left femur fracture. A muscle biopsy revealed variation in fiber size with occasional hypertrophic fibers. The postmortem examination revealed loss and degeneration of anterior horn cells. We propose that the patient, who presented with severe hypotonia, femur fracture, arthrogryposis, dysmorphic features, history of early death of his brother with the same clinical features and parental consanguinity, had probable X-linked spinal muscular atrophy. However, autosomal-recessive inheritance can not be completely excluded.