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Introduction: Aminoacyl transfer RNA (tRNA) synthetases are associated with diseases when mutations occur in their encoding genes. Pulmonary alveolar proteinosis can be caused by mutation in the methionyl-tRNA synthetase (MARS) gene while mutations in the leucine-tRNA synthetase (LARS) gene lead to infantile liver failure syndrome type 1. We report the case of a patient with LARS1 pathogenics variants and two patients with MARS1 pathogenics variants. The aim of this study was to analyze the phenotypes of our three patients in detail and classify cases in the literature using Human Phenotype Ontology (HPO) terms., Results: The first patient has two previously undescribed heterozygous variants in LARS1 (c.1818dup and c.463A>G). The other two patients' MARS1 variants (c.1177G>A and c.1700C>T) have already been described in the literature. All three patients had anemia, hepatomegaly, feeding difficulties, failure to thrive and hypoalbuminemia. Including ours, 65 patients are described in total, for whom 117 phenotypic abnormalities have been described at least once, 41.9% of which both in patients with LARS1 and MARS1 mutations., Conclusion: Patients with LARS1 and MARS1 mutations seem to share a common phenotype but further deep phenotyping studies are required to clarify the details of these complex pathologies., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

The clinical picture associated with a Transport and Golgi Organization 2 (TANGO2) gene bi-allelic mutation is represented by encephalopathy and rhabdomyolysis marked by cardiac rhythm disorders and neurological regression. The presentation of encephalopathy is diverse and can range from isolated language delay and cognitive impairment in a child to multiple disabilities and spastic quadriparesis. Hypothyroidism has also been frequently reported. This article presents the clinical phenotype of seven children with a TANGO2 bi-allelic mutation. The mutation was found by sequencing a panel of genes associated with rhabdomyolysis. While the clinical picture represents generalized cases, there is phenotypic variability in, for example, the degree of disability for each patient. A TANGO2 gene mutation, nevertheless, represents a serious illness with a limited life expectancy due to an unpredictable risk of cardiac rhythm disorder and death, particularly during rhabdomyolysis. Although the natural history of the disease presents an evolution of rhabdomyolysis triggered by infections or effort, an early diagnosis is difficult due in part to the fact that there is a lack of specific biochemical marker or identifying symptoms in the early presentation of the disease. Clinicians must therefore consider the TANGO2 gene when confronted with rhabdomyolysis in a patient suffering from an early developmental disorder. In the meantime, management of the disease remains purely symptomatic., (Copyright © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Acute liver failure (ALF) in childhood is a life-threatening emergency. ALF is often caused by drug toxicity, autoimmune hepatitis, inherited metabolic diseases, and infections. However, despite thorough investigations, a cause cannot be determined in approximately 50% of cases. Here, we report three cases with recurrent ALF caused by NBAS and SCYL1 pathogenic variants. These patients did not present with any other phenotypic sign usually associated with NBAS and SCYL1 pathogenic variants. Two of them underwent liver transplantation and are healthy without recurrence of ALF. We propose NBAS and SCYL1 genetic analysis in children with unexplained fever-triggered recurrent ALF even without a typical phenotype., (Copyright © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Charcot-Marie-Tooth disease (CMT) is an inherited peripheral neuropathy with an impact on patients' quality of life and wide genetic heterogeneity. Next-generation sequencing (NGS) has extended the molecular diagnosis. This study aims to describe a cohort of patients with CMT onset in childhood to explore genotype-phenotype correlations., Material and Methods: This is a retrospective and single-center study. Between 1992 and 2016, patients with CMT diagnosed in childhood and a molecular diagnosis were included. The follow-up was done at the Marseille Timone Teaching hospital and symptoms were retrieved over time in the patients' files, as well as from molecular data and an electrodiagnostic exam. We distinguished three groups: PMP22 compared CMT (CMT1A), MFN2 compared CMT (CMT2A2) and "all genes except PMP22"., Results: Seventy-five patients were included with 11 different genes involved, PMP22 being the most frequent (61.3%), then MFN2 (14.7%) and other sporadic mutations in various genes. Limitations in walking tended to occur earlier and more often, and distal strength impairment tended to progress further in CMT2A2 and "others genes than PMP22". The mean age at diagnosis was 8.4 years with a mean age when parents first expressed concern of 4.1 years. Only three patients lost their ability to walk. We describe two cases of digenism and one case of GAN mutation with a CMT-like presentation. An electromyogram was not systemically performed., Conclusion: There is a wide genetic and clinical heterogeneity in CMT. We tend to describe more severe patterns in CMT2A2 and less progressive presentations in CMT1A considering distal strength impairment and limitations walking. Prospective studies with more objective principal judgement criteria would be necessary to confirm these observations., (Copyright © 2018. Published by Elsevier Masson SAS.)