Background Aromatic l‐amino acid decarboxylase deficiency (AADCD) is a rare, early‐onset, dyskinetic encephalopathy mostly reflecting a defective synthesis of brain dopamine and serotonin. Intracerebral gene delivery (GD) provided a significant improvement among AADCD patients (mean age, ≤6 years). Objective We describe the clinical, biological, and imaging evolution of two AADCD patients ages >10 years after GD. Methods Eladocagene exuparvovec, a recombinant adeno‐associated virus containing the human complimentary DNA encoding the AADC enzyme, was administered into bilateral putamen by stereotactic surgery. Results Eighteen months after GD, patients showed improvement in motor, cognitive and behavioral function, and in quality of life. Cerebral l‐6‐[18F] fluoro‐3, 4‐dihydroxyphenylalanine uptake was increased at 1 month, persisting at 1 year compared to baseline. Conclusion Two patients with a severe form of AADCD had an objective motor and non‐motor benefit from eladocagene exuparvovec injection even when treated after the age of 10 years, as in the seminal study.

Background and purpose: HIBCH and ECHS1 genes encode two enzymes implicated in the critical steps of valine catabolism, 3-hydroxyisobutyryl-coenzyme A (CoA) hydrolase (HIBCH) and short-chainenoyl-CoA hydratase (ECHS1), respectively. HIBCH deficiency (HIBCHD) and ECHS1 deficiency (ECHS1D) generate rare metabolic dysfunctions, often revealed by neurological symptoms. The aim of this study was to describe movement disorders spectrum in patients with pathogenic variants in ECHS1 and HIBC. Methods:We reviewed a series of 18 patients (HIBCHD: 5; ECHS1D: 13) as well as 105 patients from the literature. We analysed the detailed phenotype of HIBCHD (38 patients) and ECHS1D (85 patients), focusing on MDs. Results:The two diseases have a very similar neurological phenotype, with an early onset before 10 years of age for three clinical presentations: neonatal onset, Leigh-like

We present the phenotype of an infant with the largest ATN1 CAG expansion reported to date (98 repeats). He presented at 4 months with developmental delay, poor eye contact, acquired microcephaly, failure to thrive. He progressively developed dystonia‐parkinsonism with paroxysmal oromandibular and limbs dyskinesia and fatal outcome at 17 months. Cerebral MRI disclosed globus pallidus T2‐WI hyperintensities and brain atrophy. Molecular analysis was performed post‐mortem following the diagnosis of dentatorubral–pallidoluysian atrophy (DRPLA) in his symptomatic father. Polyglutamine expansion defects should be considered when neurodegenerative genetic disease is suspected even in infancy and parkinsonism can be a presentation of infantile‐onset DRPLA.