Migalastat Treatment in a Kidney-Transplanted Patient with Fabry Disease and N215S Mutation: The First Case Report.

Fabry disease is a rare X-linked lysosomal storage disorder caused by mutations in the GLA gene, leading to deficient α-galactosidase A activity and, consequently, to glycosphingolipid accumulation in a wide variety of cells. Fabry disease due to N215S (c.644A>G, p.Asn215Ser) missense mutation usually results in a late-onset phenotype presenting with isolated cardiac involvement. We herein present the case of a patient with N215S mutation with cardiac involvement, namely left ventricular hypertrophy and ventricular arrhythmias, and end-stage renal disease requiring kidney transplantation. To the best of our knowledge, this is the first report of a kidney-transplanted Fabry patient treated with oral pharmacologic chaperone migalastat.

Utility of hospitalization for elderly individuals affected by COVID-19.

BACKGROUND: During the COVID-19 pandemic, the number of individuals needing hospital admission has sometimes exceeded the availability of hospital beds. Since hospitalization can have detrimental effects on older individuals, preference has been given to younger patients. The aim of this study was to assess the utility of hospitalization for elderly affected by COVID-19. We hypothesized that their mortality decreases when there is greater access to hospitals. METHODS: This study examined 1902 COVID-19 patients consecutively admitted to three large hospitals in Milan, Italy. Overall mortality data for Milan from the same period was retrieved. Based on emergency department (ED) data, both peak and off-peak phases were identified. The percentage of elderly patients admitted to EDs during these two phases were compared by calculating the standardized mortality ratio (SMR) of the individuals younger than, versus older than, 80 years. RESULTS: The median age of the patients hospitalized during the peak phase was lower than the median age during the off-peak phase (64 vs. 75 years, respectively; p <0.001). However, while the SMR for the younger patients was lower during the off-peak phase (1.98, 95% CI: 1.72-2.29 versus 1.40, 95% CI: 1.25-1.58, respectively), the SMR was similar between both phases for the elderly patients (2.28, 95% CI: 2.07-2.52 versus 2.48, 95% CI: 2.32-2.65, respectively). CONCLUSIONS: Greater access to hospitals during an off-peak phase did not affect the mortality rate of COVID-19-positive elderly patients in Milan. This finding, if confirmed in other settings, should influence future decisions regarding resource management of health care organizations.

Management of age-associated medical complications in patients with ß-thalassemia.

Introduction: ß-Thalassemia syndromes are among the most common monogenic disorders worldwide. Clinically, on the basis of the severity of the phenotype, ß-thalassemias are classified into two groups: transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT). In the last few decades, considerable advances in understanding the pathophysiology of ß-thalassemia have significantly improve d patient management, which has led to an increase in the life span of these subjects. However, new complications associated with aging are emerging, and ß-thalassemias are becoming a growing concern for the health care systems.Areas covered: The present review focused on the age-related complications in adults with ß-thalassemia. Among the cardiovascular diseases, which remain a major cause of morbidity, pulmonary hypertension and arrhythmias are exhibiting increased prevalence. Adrenal insufficiency and bone disease are emerging as endocrinological complications that require proper treatment. Moreover, age-related complications observed in the general population, including cancers and renal disease, should not be neglected.Expert opinion: The present study reviews the management of above-stated complications in adults with ß-thalassemia based on the experience of a referral center. It is noteworthy that clinical trials in this context are limited, and the expert opinion offered in the present report stems mainly from direct clinical experience.

Low-dose Synachten test with measurement of salivary cortisol in adult patients with ß-thalassemia major.

PURPOSE: Beta-thalassemia major is a severe, congenital hematological disorder and, if untreated, leads to early mortality. Progress in therapeutical strategies improved clinical outcomes and life expectancy; however, increased survival led to the development of new disorders, including endocrinopathies. Little is known on the possible impairment of adrenocortical function, a potentially life-threatening condition, in long-term thalassaemic survivors. We therefore decided to assess adrenal reserve and the value of salivary cortisol during ACTH stimulation in the diagnosis of adrenocortical insufficiency in adult patients with ß-thalassemia major. METHODS: Cross-sectional study including 72 adults with ß-thalassemia major. Patients were tested with 1 µg ACTH for serum and salivary cortisol. RESULTS: Subnormal serum cortisol responses to ACTH stimulation (i.e., <500 nmol/l) were registered in 15 out of 72 patients. Salivary cortisol increased in parallel with serum cortisol and a clear-cut positive correlation was detected at each timepoint. Moreover, peak salivary cortisol values after ACTH stimulation were significantly lower in patients with impaired adrenal reserve (513.6 ± 52.33 vs. 914.1 ± 44.04 nmol/l p < 0.0001). CONCLUSIONS: Our results attest to the need for testing for adrenal insufficiency among adult thalassaemic patients, as up to 20% presented impaired adrenal reserve. Salivary and serum cortisol levels during stimulation with ACTH were closely correlated and the use of salivary cortisol sampling during ACTH testing may represent a surrogate to serum cortisol in these patients.