ObjectiveGenetic diagnosis and mutation identification are now compulsory for Duchenne (DMD) and Becker muscular dystrophies (BMD), which are due to dystrophin (DMD) gene mutations, either for disease prevention or personalized therapies. To evaluate the ethnic-related genetic assortments of DMD mutations, which may impact on DMD genetic diagnosis pipelines, we studied 328 patients with DMD and BMD from non-European countries.MethodsWe performed a full DMD mutation detection in 328 patients from 10 Eastern European countries (Poland, Hungary, Lithuania, Romania, Serbia, Croatia, Bosnia, Bulgaria, Ukraine, and Russia) and 2 non-European countries (Cyprus and Algeria). We used both conventional methods (multiplex ligation-dependent probe amplification [MLPA] followed by gene-specific sequencing) and whole-exome sequencing (WES) as a pivotal study ran in 28 patients where DMD mutations were already identified by standard techniques. WES output was also interrogated for DMD gene modifiers.ResultsWe identified DMD gene mutations in 222 male patients. We identified a remarkable allele heterogeneity among different populations with a mutation landscape often country specific. We also showed that WES is effective for picking up all DMD deletions and small mutations and its adoption could allow a detection rate close to 90% of all occurring mutations. Gene modifiers haplotypes were identified with some ethnic-specific configurations.ConclusionsOur data provide unreported mutation landscapes in different countries, suggesting that ethnicity may orient genetic diagnosis flowchart, which can be adjusted depending on the mutation type frequency, with impact in drug eligibility.

AimsConsidering the substantial variability in treatment response across patients with spinal muscular atrophy (SMA), reliable markers for monitoring response to therapy and predicting treatment responders need to be identified. The study aimed to determine if measured concentrations of disease biomarkers (total tau protein, neurofilament light chain, and S100B protein) correlate with the duration of nusinersen treatment and with scores obtained using functional scales for the assessment of motor abilities.MethodsA total of 30 subjects with SMA treated with nusinersen between 2017 and 2021 at the Department of Pediatrics, University Hospital Centre Zagreb, Croatia, were included in this study. Cerebrospinal fluid (CSF) samples were collected by lumbar puncture prior to intrathecal application of nusinersen. Protein concentrations in CSF samples were determined by enzyme‐linked immunosorbent assay in 26 subjects. The motor functions were assessed using functional motor scales.ResultsThe main finding was significantly decreased total tau correlating with the number of nusinersen doses and motor improvement in the first 18–24 months of treatment (in all SMA patients and SMA type 1 patients). Neurofilament light chain and S100B were not significantly changed after administration of nusinersen.ConclusionsThe measurement of total tau concentration in CSF is a reliable index for monitoring the biomarker and clinical response to nusinersen therapy in patients with SMA.

BackgroundThe aim of this study was to assess sleep architecture and respiration during sleep in children with intractable epileptic encephalopathies using overnight video-polysomnography (V-PSG).Material/MethodsBetween 2015 to 2017 overnight V-PSG recordings were made for 31 children (22 boys and 9 girls) with intractable epileptic encephalopathy with a mean age of 6.78±3.61 years and a mean body mass index (BMI) of 15.83±3.16 kg/m3. Thirty-one healthy children were matched for sex, age, and BMI as the control group. The phases of sleep studied included rapid eye movement (REM) sleep, and non-REM (NREM) phases NREM 1, NREM 2, and NREM 3. Respiratory function during sleep was evaluated.ResultsChildren with epileptic encephalopathies receiving antiepileptic treatment had significantly decreased total sleep time (TST) (p=0.038), significantly increased percentage of NREM1 (p=0.033), and a significantly lower percentage of total REM (p<0.0001), compared with the control group. All children 31/31 (100%) with epileptic encephalopathies had interictal epileptiform discharges, and 4/31 (12.9%) had ictal events. The number of respiratory events did not differ significantly between the two groups (p=0.118), but children in the epileptic encephalopathy group had a significantly shorter average duration (p=0.008) and longest duration (p=0.048) of respiratory events. Average (p=0.006) and least (p=0.0004) oxygen saturation (SatO2) were significantly lower in children with epileptic encephalopathies compared with the control group.ConclusionsChildren with epileptic encephalopathies had altered sleep architecture and marked oxygen desaturation, which supports the need for referral of children with epileptic encephalopathy for overnight sleep evaluation.

Background Hyperammonemic encephalopathy in newborns with urea cycle disorders and certain organic acidurias can cause severe brain injury, coma and death. Standard therapy includes protein restriction, nitrogen-scavenging drugs, prevention of catabolism and hemodialysis. Neuroprotective hypothermia as part of the treatment has been reported only 3 times. It has been suggested that mild systemic hypothermia can contribute to better neurological outcomes in hyperammonemic encephalopathy. However, the limited experience precludes accurate conclusions on safety and efficacy. Methods Whole body therapeutic hypothermia was included in the standard treatment of hyperammonemic encephalopathy in 4 neonates with urea cycle disorder or organic aciduria. Results Two patients survived the initial crisis. One patient has a developmental quotient of 0.8, while the other shows severe developmental delay. The cooling protocol had to be discontinued in 3 patients due to the otherwise untreatable complications (hypotension and hemorrhage). Conclusion The efficacy and safety of therapeutic hypothermia in the treatment of neonatal hyperammonemic encephalopathy depend on various factors, requiring further evaluation.

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