Methanol poisonings occur frequently globally, but reports of larger outbreaks where complete clinical and laboratory data are reported remain scarce. The objective of the present study was to report the data from the mass methanol poisoning in the Czech Republic in 2012 addressing the general epidemiology, treatment, and outcomes, and to present a protocol for the use of fomepizole ensuring that the antidote was provided to the most severely poisoned patients in the critical phase. A combined prospective and retrospective case series study of 121 patients with confirmed methanol poisoning. From a total of 121 intoxicated subjects, 20 died outside the hospital and 101 were hospitalized. Among them, 60 survived without, and 20 with visual/CNS sequelae, whereas 21 patients died. The total and hospital mortality rates were 34% and 21%, respectively. Multivariate regression analysis found pH < 7.0 (OR 0.04 (0.01-0.16), p < 0.001), negative serum ethanol (OR 0.08 (0.02-0.37), p < 0.001), and coma on admission (OR 29.4 (10.2-84.6), p < 0.001) to be the only independent parameters predicting death. Continuous hemodialysis was used more often than intermittent hemodialysis, but there was no significant difference in mortality rate between the two [29% (n = 45) vs 17% (n = 30), p = 0.23]. Due to limited stockpiles of fomepizole, ethanol was administered more often; no difference in mortality rate was found between the two [16% (n = 70) vs. 24% (n = 21), p = 0.39]. The effect of folate administration both on the mortality rate and on the probability of visual sequelae was not significant (both p > 0.05). Severity of metabolic acidosis, state of consciousness, and serum ethanol on admission were the only significant parameters associated with mortality. The type of dialysis or antidote did not appear to affect mortality. Recommendations that were issued for hospital triage of fomepizole administration allowed conservation of valuable antidote in this massive poisoning outbreak for those patients most in need.

Information on the prognosis and electrophysiological follow-up of severe thallium poisoning is limited. We report two patients (mother and daughter) who were repeatedly exposed to thallium poisoning experienced hair loss, polyneuropathy, and visual impairment. Nerve conduction studies (NCSs), visual evoked potentials (VEP), brainstem auditory evoked potentials (BAEP) changes, and optical neuropathy developed within a few months latency after the first subjective signs. Normal findings of these electrophysiological methods in the first 2 weeks therefore led in one of our patients to exclusion of thallium as the cause of symptoms. Thallium poisoning was, however, later confirmed by toxicological analysis of blood and/or urine and feces in both the patients and in the microscopic hair analysis of the daughter. Both patients were treated with Prussian blue that increased the elimination of thallium in urine and feces. The hair loss was fully reversible. During a 2-year follow-up after the poisoning, polyneuropathy in the lower extremities improved substantially, but residual impairment in both motor and sensory function, NCSs, VEP, and BAEP remained. Additionally, severe asymmetrical vision impairment persists in both women, with central scotomata and impaired color discrimination in both eyes. Substantial improvement of their visual function is unlikely.

Background—: Hypertrophic cardiomyopathy with severe left ventricular diastolic dysfunction has been associated with marked exercise intolerance and poor prognosis. However, molecular pathogenesis of this phenotype remains unexplained in a large proportion of cases. Methods and Results—: We performed whole exome sequencing as an initial genetic test in a large Czech family with 3 males affected by nonobstructive hypertrophic cardiomyopathy with severe left ventricular diastolic dysfunction in end-stage disease. A novel frameshift mutation of four-and-a-half LIM domain 1 gene ( FHL1 ) (c.599_600insT; p.F200fs32X) was detected in these individuals. The mutation does not affect transcription, splicing, and stability of FHL1 mRNA and results in production of truncated FHL1 protein, which is contrary to heart tissue homogenate not detectable in frozen tissue sections of myocardial biopsy of affected males. The identified mutation cosegregated also with abnormal ECG and with 1 case of apical hypertrophic cardiomyopathy in heterozygous females. Although skeletal muscle involvement is a common finding in FHL1-related diseases, we could exclude myopathy in all mutation carriers. Conclusions—: We identified a novel FHL1 mutation causing isolated hypertrophic cardiomyopathy with X-chromosomal inheritance.

Background: The pleomorphic clinical presentation makes the diagnosis of desminopathy difficult. We aimed to describe the prevalence, phenotypic expression, and mitochondrial function of individuals with putative disease-causing desmin (DES) variants identified in patients with an unexplained etiology of cardiomyopathy. Methods: A total of 327 Czech patients underwent whole exome sequencing and detailed phenotyping in probands harboring DES variants. Results: Rare, conserved, and possibly pathogenic DES variants were identified in six (1.8%) probands. Two DES variants previously classified as variants of uncertain significance (p.(K43E), p.(S57L)), one novel DES variant (p.(A210D)), and two known pathogenic DES variants (p.(R406W), p.(R454W)) were associated with characteristic desmin-immunoreactive aggregates in myocardial and/or skeletal biopsy samples. The individual with the novel DES variant p.(Q364H) had a decreased myocardial expression of desmin with absent desmin aggregates in myocardial/skeletal muscle biopsy and presented with familial left ventricular non-compaction cardiomyopathy (LVNC), a relatively novel phenotype associated with desminopathy. An assessment of the mitochondrial function in four probands heterozygous for a disease-causing DES variant confirmed a decreased metabolic capacity of mitochondrial respiratory chain complexes in myocardial/skeletal muscle specimens, which was in case of myocardial succinate respiration more profound than in other cardiomyopathies. Conclusions: The presence of desminopathy should also be considered in individuals with LVNC, and in the differential diagnosis of mitochondrial diseases.