[Neuro-otological manifestations in Fabry disease-a retrospective single center study]. / Neurootologische Manifestationen bei Morbus Fabry ­ eine retrospektive Analyse.

BACKGROUND: Fabry disease (FD) is one of the X­linked lysosomal storage diseases that can affect any organ. They have a specific lysosomal dysfunction in common, which results in substrate accumulation in lysosomes instead of metabolite degradation. Due to the deficiency/absence of α­galactosidase, globotriaosylceramides (Gb3) are deposited in lysosomes of the organs. In addition to acroparesthesia, angiokeratomas, autonomic dysfunction, vortex keratopathies, ischemic cerebral or cardiac complications and chronic renal failure, also vestibulocochlear dysfunctions with sudden or progressive asymmetric hearing loss, tinnitus and vertigo may be observed. PATIENTS AND METHODS: In this retrospective study, 33 patients (men = 16 and women = 17) with FD were evaluated. All patients presented to us in interdisciplinary cooperation as part of routine examinations by the specialized center for lysosomal storage diseases of the in-house department of nephrology. This presentation is carried out as a screening examination independent of neuro-otological symptoms. RESULTS: The mean age at diagnosis was 34.76 (±11.55) years. The first presentation in our ENT department was at 40.45 (±11.71) years. We were able to demonstrate a significant correlation between neurological symptoms or apoplexy and hearing loss (p = 0.001) and between cardiac manifestations and hearing loss (p = 0.024). CONCLUSION: Hearing loss is a potential symptom of Fabry disease and is not limited to the classic male phenotype. Due to possible positive correlations with neurological and cardiological manifestations of the disease, routine ENT screening examinations should be carried out to be able to identify and treat neuro-otological deficits at an early stage. In addition, FD should also be considered and tested as a differential diagnosis, especially in younger patients with sudden unilateral or bilateral hearing loss and a family history.

Management, vaccination status and COVID-19 morbidity of patients with Gaucher disease in Germany during the COVID-19 pandemic.

BACKGROUND: Continuation of standard management of Gaucher disease (GD) has been challenging during the COVID-19 pandemic, resulting in infrequent/missed infusions and follow-up appointments. Little data are available on the consequences of these changes and on the SARS-CoV-2 vaccinations in German GD patients. METHODS: A survey with 22 questions about GD management during the pandemic was sent to 19 German Gaucher centres. It was answered by 11/19 centres caring for 257 GD patients (almost ¾ of the German GD population); 245 patients had type 1 and 12 had type 3 GD; 240 were ≥ 18 years old. RESULTS: Monitoring intervals were prolonged in 8/11 centres from a median of 9 to 12 months. Enzyme replacement therapy (ERT) was changed to home ERT in 4 patients and substituted by oral substrate reduction therapy (SRT) in 6 patients. From March 2020 to October 2021, no serious complications of GD were documented. Only 4 SARS-CoV-2 infections were reported (1.6%). Two infections were asymptomatic and two mild; all occurred in adult type 1, non-splenectomized patients on ERT. Vaccination rate in adult GD was 79.5% (95.3% mRNA vaccines). Serious vaccination complications were not reported. CONCLUSIONS: The COVID-19 pandemic has lowered the threshold for switching from practice- or hospital-based ERT to home therapy or to SRT. No major GD complication was documented during the pandemic. Infection rate with SARS-CoV-2 in GD may rather be lower than expected, and its severity is mild. Vaccination rates are high in GD patients and vaccination was well tolerated.

Quality of life in patients with Fabry's disease: a cross-sectional study of 86 adults.

Background: Fabry disease (FD) is a multi-organ disorder associated with severe physical and psychological impairments, particularly in adulthood. To date, comprehensive data on the psychological burden of FD are lacking. The present study assessed quality of life (QOL) in a representative cohort of adults with FD. Methods: Patient-reported outcome measures were retrospectively analyzed in 86 adults with FD (49.6±16.6 years; 62.8% female) and compared to adults with congenital heart defects (ACHD) which is another lifelong disease and affliction. QOL was assessed using the European Quality of Life 5 Dimensions 5 Levels questionnaire (EQ-5D-5L). Results: Subjects affected by FD reported an overall reduced QOL (EQ-VAS: 71.8±20.0). Most frequently reported complaints occurred within the dimensions pain/discomfort (69.7%), daily activities (48.9%) and anxiety/depression (45.4%). Compared to ACHD, individuals with FD scored significantly lower in the areas of pain/discomfort, usual activities and mobility (all P<0.05). Older age and female sex were particularly associated with diminished QOL (P=0.05). Conclusions: Patients with FD are at high risk for impaired QOL. They require additional support to cope with disease-related challenges. Increased attention should be directed towards improving their subjective well-being to potentially increase their QOL and long-term health outcomes.

Fabry disease: what the cardiologist should consider in non-cardiac screening, diagnosis, and management-narrative review.

Fabry disease (FD) is a rare X chromosomally transmitted lysosomal storage disorders with an absence or deficiency of the enzyme alpha-galactosidase. The deposition of globotriaosylceramide (Gb3) may cause damage to all organs, particularly brain, heart and kidney. While acroparaesthesia, hypo- or anhydrosis and diarrhoea are the main symptoms in childhood, cardiac involvement with left ventricular hypertrophy (LVH), renal insufficiency, diffuse pain attacks and apoplexy are the main symptoms in adulthood. Regular examinations are necessary to record organ involvement and its progression. A major challenge is therefore to make a diagnosis at an early disease stage. This is the only way that treatment can be started if there is an indication. If FD is suspected, alpha-galactosidase should be tested in male patients and genetic testing should be performed in females to confirm the diagnosis. Since 2001, enzyme replacement therapy (ERT) has been available as a causal therapy. In 2016, chaperone therapy with the drug Migalastat was approved in the European Union, which leads to stabilisation of the defective alpha-galactosidase. Studies on gene therapy to cure FD in phase I/II. This review summarizes which patient should be screened, how to confirm the diagnosis and which examinations should be performed in FD patients during the course of the disease.

AML M1 presenting with recurrent acute large arterial vessel thromboembolism.

Acute leukemia may be associated with coagulopathy, predominantly severe bleeding diathesis caused by disseminated intravascular coagulation (DIC) and/or hyperfibrinolysis. Disordered hemostasis is characteristic for acute promyelocytic leukemia (APL, FAB M3). However, thromboembolic events such as arterial occlusion localized to the large vessels at presentation is very rare and almost exclusively linked to APL. We report a case of severe recurrent acute arterial thromboembolism at presentation in AML FAB M1. Most likely, the ischemic events in our patient resulted from leukemia as the thrombus material included many leukemic blasts. The thrombotic complications resulted in leg amputation in this patient. Despite leg amputation just a couple of hours before and extremely high infectious risk of the patient, chemotherapy was administered. The clinical course of cessation of the ischemic events and a fast reduction of the blasts in the peripheral blood smear after chemotherapeutic treatment of the patient outlines the importance and life saving role of early chemotherapy even under adverse circumstances.

C-terminal agrin fragment (CAF) as a serum biomarker for residual renal function in peritoneal dialysis patients.

BACKGROUND: C-terminal agrin fragment (CAF, size 22 kDa) is a promising new biomarker for kidney function. This study evaluated the usefulness of CAF as a serum biomarker for residual renal function (RRF) in patients undergoing automated peritoneal dialysis (APD). PATIENTS AND METHODS: Serum, urine and dialysate samples were obtained in 12 end-stage renal disease patients undergoing APD. Total, renal and peritoneal clearances were calculated for CAF, creatinine, blood urea nitrogen (BUN) and cystatin c. kt/V was computed, and RRF (in ml/min) was calculated as the arithmetic mean of creatinine and BUN clearance. Correlations between the biomarkers' serum concentrations, clearances, kt/V and RRF were computed. RESULTS: Serum CAF concentrations were highly correlated with serum concentrations of creatinine (r = 0.806, p = 0.002), BUN (r = 0.727, p = 0.007), cystatin c (r = 0.839, p = 0.001) and inversely to 24-h urinary output (r = -0.669, p = 0.017). RRF was inversely correlated with serum concentrations of CAF, cystatin c and creatinine being highest for CAF (r = -0.734, p = 0.007) followed by cystatin c (r = -0.65, p = 0.022) and creatinine (r = -0.606, p = 0.037). Serum BUN was not significantly associated with RRF (r = -0.497, p = 0.101). Age, weight and gender did not significantly affect serum CAF concentrations. CONCLUSION: Serum CAF provides a robust serum biomarker for RRF in peritoneal dialysis patients undergoing APD, possibly outperforming the value of conventional biomarkers.

Non-invasive monitoring of renal transplant recipients: urinary excretion of soluble adhesion molecules and of the complement-split product C4d.

BACKGROUND: The number of inducible adhesion molecules known to be involved in cell-mediated allograft rejection is still increasing. In addition, recent data describe complement activation during acute humoral allograft rejection. The aim of this study was to assess whether specific molecules from either pathway are excreted into urine and whether they can provide useful diagnostic tools for the monitoring of renal transplant recipients. METHODS: Urinary concentrations of soluble adhesion molecules (sICAM-1, sVCAM-1) and of the complement degradation product C4d were determined by standardized ELISA technique in 75 recipients of renal allografts and 29 healthy controls. Patient samples were assigned to four categories according to clinical criteria: GROUP 1: acute steroid-sensitive rejection (ASSR, n = 14), GROUP 2: acute steroid-resistant rejection (ASRR, n = 12), GROUP 3: chronic allograft dysfunction (CAD, n = 20) and GROUP 4: stable graft function (SGF, n = 29). RESULTS: All patients with rejection episodes (groups 1-3) had significantly higher values of urinary sC4d compared with healthy controls and patients with stable graft function (p < 0.05). The urinary levels of sVCAM-1 were significantly higher in group 2 (ASRR) compared with all other groups (p < 0.001). Uniformly low amounts of s-VCAM-1 and complement-split product C4d were excreted by healthy controls (group 0). In contrast, urinary sICAM-1 concentration in healthy controls was almost as high as in group 2 (ASRR) whereas patients with a stable functioning graft (group 4) excreted significantly less sICAM-1 (p < 0.05). CONCLUSION: The evaluation of sVCAM-1 and sC4d excretion in urine can provide a valuable tool with regard to the severity and type of allograft rejection. With respect to long-term allograft survival, serial measurements of these markers should have the potential to detect rejection episodes and prompt immediate treatment.