Aromatic L-amino acid decarboxylase deficiency (AADCd) is a rare recessive metabolic disorder caused by pathogenic homozygous or compound heterozygous variants in the dopa decarboxylase (DDC) gene. Adeno-associated viral vector-mediated gene transfer of the human DDC gene injected into the putamen is available. The typical presentation is characterized by early-onset hypotonia, severe developmental delay, movement disorders, and dysautonomia. Recently, mild and even atypical phenotypes have been reported, increasing the diagnostic challenge. The aim of this multicentric study is to identify the prevalence of AADCd in a population of patients with phenotypic clusters characterized by neurodevelopmental disorders (developmental delay/intellectual disability, and/or autism) by 3-O-methyldopa (3-OMD) detection in dried blood spots (DBS). It is essential to identify AADCd promptly, especially within non-typical phenotypic clusters, because better results are obtained when therapy is quickly started in mild-moderate phenotypes. Between 2021 and 2023, 390 patients with non-specific phenotypes possibly associated with AADCd were tested; none resulted in a positive result. This result highlights that the population to be investigated for AADCd should have more defined clinical characteristics: association with common signs (hypotonia) and/or pathognomonic symptoms (oculogyric crisis and dysautonomia). It is necessary to continue to screen selected clusters for reaching diagnosis and improving long-term outcomes through treatment initiation. This underscores the role of newborn screening in identifying AADCd.

Myelin oligodendrocyte glycoprotein (MOG)-IgG-associated disease (MOGAD) is a relatively uncommon autoantibody demyelinating disorder of the central nervous system (CNS) with heterogeneous clinical manifestations and magnetic resonance imaging (MRI) findings. In recent years, a rare MOGAD subtype characterized by distinct clinical and MRI findings has been described. Seizures and cortical hyperintensities best seen on MRI T2-weighted fluid-attenuated inversion recovery (FLAIR) sequences, associated with headache and cerebral spine fluid (CSF) pleocytosis, are the most important characteristics of this MOGAD entity that is named FLAMES (FLAIR hyperintense cortical lesions in MOG-associated encephalitis with seizures). Because of its rarity and the peculiarities of the brain damage and clinical manifestations, it can be under-recognized and confused with focal viral encephalitis, meningitis, subarachnoid hemorrhage, CNS vasculitis, or mitochondrial cytopathy. We described the case of a 4-year-old previously healthy girl who was admitted for focal-onset, tonic-clonic seizures, fever, and headache, combined with optic neuritis. MRI was characterized by FLAIR imaging showing hyperintense cortical lesions, and a mild leukocytosis in the CSF was detected. Efficacy and rapid response to steroid therapy was observed, and no recurrences of neurological problems or further seizures were reported in the following 12 months. This case report can help in understanding FLAMES characteristics in pediatrics in order to favor early diagnosis and prompt therapy.

Spinal Muscular Atrophy (SMA) is a genetic disorder characterized by the progressive loss of motor neurons and consequent muscle atrophy. Although SMN-targeted therapies have significantly improved survival and motor outcomes, residual muscle weakness remains a major clinical challenge, particularly in patients treated later in the disease course. Myostatin, a potent negative regulator of skeletal muscle mass, has emerged as a promising therapeutic target to address this gap. This review summarizes the preclinical and clinical evidence supporting the modulation of the myostatin pathway in SMA. Preclinical studies have demonstrated that inhibiting myostatin, especially when combined with SMN-enhancing agents, can increase muscle mass, improve motor function, and enhance neuromuscular connectivity in SMA mouse models. These findings provide a strong rationale for translating myostatin inhibition into clinical practice as an adjunctive strategy. Early clinical trials investigating myostatin inhibitors have shown favorable safety profiles and preliminary signs of target engagement. However, large-scale trials have yet to demonstrate widespread, robust efficacy across diverse patient populations. Despite this, myostatin pathway inhibition remains a compelling approach, particularly when integrated into broader treatment paradigms aimed at enhancing motor unit stability and function in individuals with SMA. Further clinical research is essential to validate efficacy, determine optimal timing, and define the patient subgroups most likely to benefit from myostatin-targeted therapies.

Purpose: To report our experience with a case of a very atypical clinical onset of multiple sclerosis in a young boy during a COVID-19 infection. Case report: A 16-year-old boy was referred to our ophthalmology clinic with a complete isolated bilateral horizontal gaze palsy. The condition had onset suddenly 2 weeks prior and he had no associated symptoms, as well as no significant medical history. His corrected visual acuity was 0.0 logMAR in both eyes. While hospitalized, he was found infected with COVID-19. Subsequent brain MRI showed multiple lesions typical of a yet undiagnosed MS, as well as an active pontine plaque which was highly probable the cause of the horizontal gaze palsy. High-dose steroid treatment was initiated 1 week later, after the patient exhibited negative COVID-19 test results. Conclusion: Clinical manifestations of MS are rarely seen in male teenagers and only a few cases of isolated bilateral horizontal gaze palsy have been reported as the initial manifestation, but never during concomitant COVID-19 infection. We presume that the presence of COVID-19 may have been a neuroinflammatory trigger of underlying MS.