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Inborn errors of metabolism (IEM) are genetic disorders due to a defective metabolic pathway. The incidence of each disorder is variable and depends on the respective population. Some disorders such as urea cycle disorders (UCD) and organic acidurias, pose a high risk for a metabolic crisis culminating in a life-threatening event, especially during infections; thus, vaccines may play a crucial role in prevention. However, there are different triggers for decompensations including the notion that vaccines themselves can activate fever and malaise. Additionally, many of the IEM include immunodeficiency, placing the patients at an increased risk for infectious diseases and possibly a weaker response to immunizations. Since metabolic crises and vaccine regimens intersect in the first years of life, the question whether to vaccinate the child occupies parents and medical staff. Many metabolic experts hesitate to vaccinate IEM patients, disregarding the higher risk from the direct infections. In this paper we summarize the published data regarding the safety and recommendations for vaccinations in IEM patients, with reference to the risk for decompensations and to the immunogenic component.

Aim: In pyridoxine dependent epilepsy (PDE), patients usually present with neonatal seizures. Received 21 March 2017 A small subgroup is characterized by late-onset beyond 2 months of age. We aim to analyze the Received in revised form observation of relatively good cognitive outcome in this subgroup of late-onset PDE patients.Methods: We retrospectively analyzed data from four metabolically and genetically Accepted 25 March 2018 confirmed late-onset patients with PDE due to antiquitin (ALDH7A1) deficiency. Data were analyzed regarding ALDH7A1 mutations, alpha-Aminoadipic semialdehyde (alpha-AASA) and Keywords: pipecolic acid (PA) levels, medication during pregnancy, delivery, treatment delay, amount Pyridoxine dependent epilepsy of seizures, pyridoxine dose, adjuvant therapy and findings on brain MRI.Results: Results showed that three patients had relatively good outcome (IQ 80-97), while one patient did not undergo formal testing and was considered mildly delayed. We were unable to find a clear association between the above-mentioned variables and cognitive outcome, although a less severe genotype may be present in three patients, and maternal medication could be accountable for better outcome in two patients.Interpretation: We suggest that favorable outcome in late onset PDE might be explained by a combination of factors. A yet unknown protective factor, different genetic variations, functional variation and secondarily variation in treatment regimens and absence of neonatal seizure induced brain damage. (C) 2018 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Objective Clinical metabolomics has emerged as a powerful tool to study metabolic perturbations in various diseases and to unravel novel biomarkers. In a monocenter study on metabolic-genetic research into epileptic encephalopathies, we applied untargeted metabolomics in parallel with exome sequencing in twin brothers with epileptic encephalopathy of unknown etiology. Genetic analysis confirmed Snyder-Robinson syndrome (SRS), a rare X-linked mental retardation syndrome. The underlying spermine synthase (SMS) deficiency affects polyamine metabolism and reduces intracellular spermine. So far, the diagnosis of SRS relied on a reduced spermine/spermidine ratio in lymphoblasts and/or sequencing of the SMS gene. Case The male monozygotic twins presented with developmental delay, progressive microcephaly and discrete dysmorphic features. From the age of 12 months, they developed therapy-resistant seizures with recurrent irregular myoclonic jerks and serial spasms in twin A. The EEG showed an abnormal background activity and multifocal and generalized spike waves. Additional atonic and tonic seizures and atypical absences occurred in both. At the age of 15 months, they developed a severe encephalopathy with frequent seizures, loss of milestones, impairment of visual interaction and a transient choreo-athetotic movement disorder. Both twins showed signs of osteopenia, twin B suffered a non-traumatic clavicular fraction at 23 months. Methods Clinical exome sequencing was applied in both twins and their parents. Sanger sequencing was applied to confirm the candidate variant. An untargeted plasma metabolomics analysis was performed by liquid chromatography–high-resolution mass spectrometry (LC-MS). Results Exome sequencing revealed a novel SMS missense mutation. Discriminant statistical analysis of the LC-MS data showed a distinct plasma metabolomics profile while comparative analysis versus age-matched controls revealed significantly elevated levels of N-acetylspermidine, a metabolite involved in spermine metabolism. Conclusion A combined clinical “omics” approach revealed N-acetylspermidine as a novel plasma biomarker for spermine synthase deficiency and identified a novel missense mutation in twin boys with SRS.

Objective Characterization of clinical symptoms and disease course in children with Moyamoya angiopathy. Methods Between 2011 and 2014 34 children and adolescents were treated in the Moyamoya Center in Zurich. Evaluation comprised a detailed history, neurologic and developmental status including pediatric stroke outcome measure (PSOM). Cerebral MRI and MR angiography (MRA), conventional cerebral angiography and H215O-PET with acetazolamid challenge were performed followed by individualized treatment. Results Median age at symptom onset was 4 1/2 years (range 6 months–14 years). We found a female preponderance (female/male ratio 1.8/1). Diagnosis was Moyamoya disease in 18 and Moyamoya syndrome in 16 children. 5/16 Moyamoya syndromic children had Neurofibromatosis Type 1. Most but not all children presented with a transitory ischemic attack (TIA) or stroke. In 11 children headaches and migraine were the main complaint. Besides weakness and focal sensory deficits headache was often accompanied by peculiar and unspecific symptoms like short episodes of altered consciousness, involuntary movements, general weakness and falls. On presentation MRI revealed ischemic lesions in 21 cases. Cortical lesions were observed in 11 patients (mean age 2 years), subcortical in 10 patients (mean age 6 1/2 years). In 6 children under 3 years we found a rapid progressive angiopathy. Posterior circulation was involved in 10 patients, all of them were younger than 6 years. PSOM score tended to be higher in young children. Conclusion Early diagnosis and surgical revascularisation are mandatory for stroke prevention in Moyamoya angiopathy, especially in young toddlers. In school aged children with migraines or chronic headaches accompanied by weakness, focal sensory deficits, altered consciousness or involuntary movements it is worthwhile to consider Moyamoya angiopathy as an important differential in the diagnostic assessment.