Gustavo Rodrigues Ferreira Gomes

Background and Aims: Maple syrup urine disease (MSUD) is an inherited disorder of branched‐chain amino acid metabolism caused by deficiency of the branched‐chain α‐keto acid dehydrogenase complex. Neurological manifestations predominantly involve the central nervous system, whereas peripheral nervous system involvement has been rarely reported. Results: We report a genetically confirmed case of intermittent MSUD caused by compound heterozygous pathogenic variants in DBT in a female patient who developed recurrent ataxic episodes beginning in early childhood, followed by acute ascending weakness during metabolic decompensation at 12 years of age. Initially suspected to have Guillain–Barré syndrome, subsequent biochemical and molecular investigations established the diagnosis of MSUD. Five years later, despite good metabolic control and substantial functional recovery, follow‐up nerve conduction studies, and electromyography demonstrated a chronic demyelinating sensorimotor polyneuropathy. Clinical examination additionally revealed bilateral pes cavus and persistent mild distal lower‐limb weakness. Interpretation: Only a few cases of peripheral neuropathy associated with MSUD have previously been described. Our findings expand the phenotypic spectrum by documenting the longitudinal evolution from recurrent childhood neurological episodes to chronic mixed demyelinating–axonal polyneuropathy. The clinical course supports the hypothesis that repeated metabolic decompensation may contribute to cumulative peripheral nerve injury. Although the precise mechanisms remain uncertain, mitochondrial dysfunction, impaired energy metabolism, oxidative stress, and branched‐chain amino acid and α‐keto acid toxicity provide plausible explanations. Conclusion: Peripheral neuropathy should be recognized as a potential manifestation of MSUD, including intermittent phenotypes. Long‐term neurological follow‐up incorporating electrophysiological evaluation may improve recognition of peripheral nervous system involvement and contribute to a more complete characterization of the disease.

Background: Congenital myopathy-13 (CMYP13), also known as Bailey-Bloch congenital myopathy and Native American myopathy (NAM), is a condition caused by biallelic missense pathogenic variants in STAC3, which encodes an important protein necessary for the excitation-relaxation coupling machinery in the muscle. Patients with biallelic pathogenic variants in STAC3 often present with congenital weakness and arthrogryposis, cleft palate, ptosis, myopathic facies, short stature, kyphoscoliosis, and susceptibility to malignant hyperthermia provoked by anesthesia. We present two unrelated cases of Bailey-Bloch congenital myopathy descendants of non-consanguineous parents, which were investigated for delayed psychomotor development and generalized weakness. To the best of our knowledge, these are the first descriptions of CMYP13 in Brazil. In both patients, we found the previously described pathogenic missense variant p.Trp284Ser in homozygosity. Conclusion: We seek to highlight the need for screening for CMYP13 in patients expressing the typical phenotype of the disease even in the absence of Lumbee Native American ancestry, and to raise awareness to possible complications like malignant hyperthermia in Bailey-Bloch congenital myopathy.

Described in 2005 by Bonnefond, L. et al, IARS2 (OMIM 612801) is a mitochondrial isoleucyl-tRNA synthetase encoded in the nucleus. Phenotypically, the mutation in the IARS2 is expressed in a broad clinical spectrum, which includes Leigh Syndrome (LS) as well as extra-neurological effects. We described a 7-year-old boy who presented global developmental delay, hypotonia and epilepsy, evolving with epileptic encephalopathy. An MRI showed diffuse brain atrophy and areas of capsular changes bilaterally, while the exome showed compound heterozygous mutation in the IARS2 gene, a probable pathogenic variant inherited from the mother - p.[(Arg201His)], and a pathogenic variant inherited from the father - p.[(Trp520*)]. In the literature, we found 11 cases of patients who presented phenotypically as LS with mutation of the IARS2 gene. This report shows a patient with pathogenic variants never described in IARS2 compound heterozygosity, reinforcing the hypothesis of association of the IARS2 gene with this syndrome.

Rett syndrome (RTT) is a rare neurodevelopmental disorder usually affecting females. Most typical forms of RTT patients are hemizygous for pathogenic variants in MECP2. FOXG1 syndrome is a rare and severe neurodevelopmental disorder with a broad spectrum of clinical features which could be described as RTT-like. In this paper we describe two non related patients who presented with developmental delay, microcephaly and hyperkinetic movements. One of them had epilepsy. Diagnosis was made by exome analysis and highlights an uncommon differential diagnosis in developmental delay in children.