ABSTRACT
This case report presents the clinical course of an eight-year-old boy diagnosed with febrile infection-related epilepsy syndrome (FIRES) at the age of four. Following a febrile infection, the patient experienced his initial episode of serial generalized clonic seizures. The severity of his condition led to 11 hospital admissions, totaling 157 days of hospitalization. Anakinra was initially administered during the acute phase in 2019 but was discontinued after 29 days. In 2022, the patient experienced a chronic-phase exacerbation and underwent a second course of anakinra treatment, which demonstrated a positive effect on seizure activity. With a year of anakinra therapy, the patient exhibited significant improvement in both seizure frequency and severity. This report adds to the existing evidence supporting the potential use of anakinra in the treatment of FIRES, highlighting its effectiveness during the chronic phase and suggesting the potential benefits of subsequent administration.
ABSTRACT
BACKGROUND AND PURPOSE: Charcot-Marie-Tooth disease (CMT) is a hereditary, slowly progressive neuropathy. Currently, there are no effective pharmacological treatments or sensitive disease activity biomarkers available. The aim of this study was to demonstrate the change in plasma neurofilament light chain (NfL) over time in a CMT cohort and analyse the association between CMT severity and NfL level. METHODS: Initially, 101 CMT patients and 64 controls were enrolled in the study. Repeated evaluation was performed in 73 patients and 28 controls at a 3-year interval. Disease severity assessment included clinical evaluation with CMT Neuropathy Score version 2 (CMTNSv2). Plasma NfL concentration was measured using the Simoa (single molecule array) NfL assay. RESULTS: Plasma NfL concentration was increased in the CMT group compared with controls (p < 0.001). Overall NfL level increased over the 3-year interval in both CMT (p = 0.012) and control (p = 0.001) groups. However, in 22 of 73 CMT patients and seven of 28 controls, the NfL level decreased from the baseline. Analysing the association between 3-year change in plasma NfL and disease severity (CMTNSv2), there was no correlation in the CMT group (r = 0.228, p = 0.052) or different CMT subgroups. CONCLUSIONS: Our study verifies increased plasma NfL concentrations in patients with CMT compared with controls. Longitudinal 3-year data showed a variable change in NfL levels between CMT subtypes. There was no association between change in NfL over time and disease severity. These findings suggests that NfL is not a biomarker for CMT progression.
Subject(s)
Charcot-Marie-Tooth Disease , Humans , Charcot-Marie-Tooth Disease/diagnosis , Follow-Up Studies , Intermediate Filaments , Neurofilament Proteins , Biomarkers , Disease ProgressionABSTRACT
Background and Objectives: Genetic testing has become an integral part of health care, allowing the confirmation of thousands of hereditary diseases, including neuromuscular disorders (NMDs). The reported average prevalence of individual inherited NMDs is 3.7-4.99 per 10,000. This number varies greatly in the selected populations after applying population-wide studies. The aim of this study was to evaluate the effect of genetic analysis as the first-tier test in patients with NMD and to calculate the disease prevalence and allelic frequencies for reoccurring genetic variants. Methods: Patients with NMD from Latvia with molecular tests confirming their diagnosis in 2008-2020 were included in this retrospective study. Results: Diagnosis was confirmed in 153 unique cases of all persons tested. Next-generation sequencing resulted in a detection rate of 37%. Two of the most common childhood-onset NMDs in our population were spinal muscular atrophy and dystrophinopathies, with a birth prevalence of 1.01 per 10,000 newborns and 2.08 per 10,000 (male newborn population), respectively. The calculated point prevalence was 0.079 per 10,000 for facioscapulohumeral muscular dystrophy type 1, 0.078 per 10,000 for limb-girdle muscular dystrophy, 0.073 per 10,000 for nondystrophic congenital myotonia, 0.052 per 10,000 for spinobulbar muscular atrophy, and 0.047 per 10,000 for type 1 myotonic dystrophy. Discussion: DNA diagnostics is a successful approach. The carrier frequencies of the common CAPN3, FKRP, SPG11, and HINT1 gene variants as well as that of the SMN1 gene exon 7 deletion in the population of Latvia are comparable with data from Europe. The carrier frequency of the CLCN1 gene variant c.2680C>T p.(Arg894Ter) is 2.11%, and consequently, congenital myotonia is the most frequent NMD in our population.
ABSTRACT
Background and Objectives: Our objective was to report 2 novel variants and to reclassify previously reported alanyl-tRNA synthetase 1 (AARS1) variants associated with hereditary neuropathy and to summarize the clinical features of a previously published cohort of patients. Methods: We performed detailed neurologic and electrophysiologic assessments and segregation analysis of 2 unrelated families with Charcot-Marie-Tooth (CMT) disease with novel variants in the AARS1 gene. Via literature search, we found studies that included neuropathy cases with AARS1 variants; we then reviewed and reclassified these variants. Results: We identified 2 CMT families harboring previously unreported likely pathogenic AARS1 variants: c.1823C>A p.(Thr608Lys) and c.1815C>G p.(His605Gln). In addition, we reinterpreted a total of 35 different AARS1 variants reported in cases with neuropathy from the literature: 9 variants fulfilled the current criteria for being (likely) pathogenic. We compiled and summarized standardized clinical and genotypic information for 90 affected individuals from 32 families with (likely) pathogenic AARS1 variants. Most experienced motor weakness and sensory loss in the lower limbs. Discussion: In total, 11 AARS1 variants can currently be classified as pathogenic or likely pathogenic and are associated with sensorimotor axonal or intermediate, slowly progressive polyneuropathy with common asymmetry and variable age of symptom onset with no apparent involvement of other organ systems.
ABSTRACT
New disease-modifying treatments have recently been approved for 5q spinal muscular atrophy (SMA) and early treatment has been associated with a better clinical outcome. Accordingly, new-born screening (NBS) for SMA should be implemented to ensure early diagnosis of affected individuals. The aim of this study was to determine the feasibility and usefulness of NBS for SMA in Latvia. Between February and November of 2021, 10,411 parents consented to participation in the study. DNA testing for the SMN1 exon 7 homozygous deletion was conducted using qPCR with fluorescent locked nucleic acid primers. In the first month of testing, reporting of results took up to a maximum of 17 days after samples arrived in the laboratory. However, following familiarisation with the procedure, the median report time was reduced to 11 days after birth. Forty cases required samples to be taken again due to poor quality of the isolated DNA transpiring from either the quality of the blood punch or manual mistakes during DNA isolation. The SMN1 exon 7 homozygous deletion was identified in two individuals, which was subsequently confirmed by multiplex ligation-dependent probe amplification. When a NBS sample is taken 48 to 72 h after birth and transported to the laboratory within two working days after collection according to legal requirements, DNA test results can be reported to healthcare professionals before the 12th day of life. Expansion of our SMA 5q NBS procedure to the whole of Latvia is feasible and would facilitate early diagnosis and result in more effective treatment. We strongly advocate that SMA is added to the national Latvia Recommended Uniform Screening Panel.
