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Abstract Fabry disease (FD) constitutes a rare, X-linked lysosomal storage disorder affecting multiple organ systems, most notably heart, kidneys, and the central nervous system. Neurofilament light chains (NfL) have emerged as a prime candidate for a body fluid biomarker reflecting neuro-axonal injury. We aimed to evaluate its addition to the diagnostic and monitoring armamentarium in FD. Serum NfL concentrations (sNfL) were measured in 50 people with FD (PwFD) and 30 healthy control subjects (HC) using the Simoa© technology, followed by calculation of Z-scores adjusted for age and body mass index. In addition, clinical disease severity in PwFD was measured using the FOS-MSSI (Fabry outcome study – Mainz severity score index), which comprises clinical and paraclinical parameters. PwFD show elevated sNfL Z-scores compared to HC (PwFD: 1.12 [SD 1.5], HC: 0.01 [SD 1.2], p

Abstract Background Pregnancy and delivery outcomes in women with Fabry disease are not well described. Methods Retrospective cohort-study of women with Fabry disease in Austria using a specific questionnaire and the Austrian Mother–Child Health Passport. Results Out of a total of 44 enrolled women (median age at study entry 44 years, p25: 30, p75: 51), 86.4% showed signs and symptoms of Fabry disease with an increase in pain burden during pregnancy, primarily in women with moderate pain before pregnancy. Thirty-two of 44 women with Fabry disease reported a total of 70 pregnancies (median age at first pregnancy 24 years, p25: 21, p75: 31), 61 (87.1%) of which resulted in 64 live births including 3 sets of twins, six miscarriages (8.6%) in five women, and three induced abortions (4.3%) in two women. Risk factors for poor maternal and foetal outcomes during pregnancy, overrepresented in our cohort as compared to the general population, were hypertension (n = 10, 16.4%), proteinuria (n = 17, 27.9%) and smoking (n = 24, 39.3%). Preeclampsia was reported in 7 pregnancies (11.5%). Fifty-one (79.7%) children were born at term and 13 (20.3%) were preterm (including one neonatal death), with a median gestational age of 39 weeks (p25: 38, p75: 40) and delivery by C-section in 15 pregnancies (24.6%). Thirteen (20.3%) children presented with low birth weight and 18 (28.1%) were small for their gestational age. In comparison to global and national data-sets, preeclampsia, prematurity, low birth weight, being small for their gestational age as well as inpatient stay were significantly more common in patients with Fabry disease. Conclusions Our cohort-study in women with Fabry disease shows an increase of pain burden during pregnancies and clearly points to an increased risk for preeclampsia, prematurity, and neonates small for gestational age. With a substantial number of high-risk pregnancies, neonatal outcomes are somewhat worse in Fabry disease than in the general public. Thus, we provide valuable data enabling informed decision-making in pregnancy counselling for Fabry disease.

We describe the case of a 44-year-old male patient with a longstanding history of microhematuria and mildly impaired kidney function (CKD G2A1). The family history disclosed three females who also had microhematuria. Genetic testing by whole exome sequencing revealed two novel variants in COL4A4 (NM_000092.5: c.1181G>T, NP_000083.3: p.Gly394Val, heterozygous, likely pathogenic; Alport syndrome, OMIM# 141200, 203780) and GLA (NM_000169.3: c.460A>G, NP_000160.1: p.Ile154Val, hemizygous, variant of uncertain significance; Fabry disease, OMIM# 301500), respectively. Extensive phenotyping revealed no biochemical or clinical evidence for the presence of Fabry disease. Thus, the GLA c.460A>G, p.Ile154Val, is to be classified as a benign variant, whereas the COL4A4 c.1181G>T, p.Gly394Val confirms the diagnosis of autosomal dominant Alport syndrome in this patient.

Background: Fabry cardiomyopathy is characterized by left ventricular hypertrophy, myocardial fibrosis, arrhythmia, and premature death. Treatment with migalastat, an oral pharmacological chaperone, was associated with a stabilization of cardiac biomarkers and a reduction in left ventricular mass index, as measured by echocardiography. A recent study, using cardiac magnetic resonance (CMR) as the gold standard, found a stable course of myocardial involvement after 18 months of treatment with migalastat. Our study aimed to provide long-term CMR data for the treatment with migalastat. Methods: A total of 11 females and four males with pathogenic amenable GLA mutations were treated with migalastat and underwent 1.5T CMR imaging for routine treatment effect monitoring. The main outcome was a long-term myocardial structural change, reflected by CMR. Results: After migalastat treatment initiation, left ventricular mass index, end diastolic volume, interventricular septal thickness, posterior wall thickness, estimated glomerular filtration rate, and plasma lyso-Gb3 remained stable during the median follow-up time of 34 months (min.: 25; max.: 47). The T1 relaxation times, reflecting glycosphingolipid accumulation and subsequent processes up to fibrosis, fluctuated over the time without a clear trend. No new onset of late gadolinium enhancement (LGE) areas, reflecting local fibrosis or scar formation of the myocardium, could be detected. However, patients with initially present LGE showed an increase in LGE as a percentage of left ventricular mass. The median α-galactosidase A enzymatic activity increased from 37.3% (IQR 5.88–89.3) to 105% (IQR 37.2–177) of the lower limit of the respective reference level (p = 0.005). Conclusion: Our study confirms an overall stable course of LVMi in patients with FD, treated with migalastat. However, individual patients may experience disease progression, especially those who present with fibrosis of the myocardium already at the time of therapy initiation. Thus, a regular treatment re-evaluation including CMR is needed to provide the optimal management for each patient.

Background: Police first responder systems also including automated external defibrillation (AED) has in the past shown considerable impact on favourable outcomes after out-of-hospital cardiac arrest (OHCA). While short hands-off times in chest compressions are known to be beneficial, various AED models use different algorithms, inducing longer or shorter durations of crucial timeframes along basic life support (BLS). Yet, data on details of these differences, and also of their potential impact on clinical outcomes are scarce. Methods: For this retrospective observational study, patients with OHCA of presumed cardiac origin and initially shockable rhythm treated by police first responders in Vienna, Austria, between 01/2013 and 12/2021 were included. Data from the Viennese Cardiac Arrest Registry and AED files were extracted, and exact timeframes were analyzed. Results: There were no significant differences in the 350 eligible cases in demographics, return of spontaneous circulation, 30-day survival, or favourable neurological outcome between the used AED types. However, the Philips HS1 and -FrX AEDs showed immediate rhythm analysis after electrode placement (0 [0–1] s) and almost no shock loading time (0 [0–1] s), as opposed to the LP CR Plus (3 [0–4] and 6 [6–6] s, respectively) and LP 1000 (3 [2–10] and 6 [5–7] s, respectively). On the other hand, the HS1 and -FrX had longer analysis times of 12 [12–16] and 12 [11–18] s than the LP CR Plus (5 [5–6] s) and LP 1000 (6 [5–8] s). The duration from when the AED was turned on until the first defibrillation were 45 [28–61] s (Philips FrX), 59 [28–81] s (LP 1000), 59 [50–97] s (HS1), and 69 [55–85] s (LP CR Plus). Conclusion: In a retrospective analysis of OHCA-cases treated by police first responders, we could not find significant differences in clinical patient outcomes concerning the respective used AED model. However, various differences in time durations (e.g., electrode placement to rhythm analysis, analysis duration, or AED turned on until first defibrillation) along the BLS algorithm were seen. This opens up the question of AED-adaptations and tailored training methods for professional first responders.