RESUMO
Collagen VI-related disorders constitute a spectrum of severities from the milder Bethlem myopathy (BM) to the Ullrich congenital muscular dystrophy (UCMD), which is more severe, and an intermediate form characterized by muscle weakness that begins in infancy. Affected children are able to walk, although walking becomes increasingly difficult starting in early adulthood. They develop contractures in the ankles, elbows, knees, and spine in childhood. In some affected cases, the respiratory muscles are weakened, requiring mechanical ventilation, particularly during sleep. Individuals with collagen VI-related myopathy are at risk of restrictive lung disease and sleep-disordered breathing due to the development of scoliosis associated with neuromuscular weakness. Typical signs of respiratory failure are not always present, and some patients are unaware that their respiratory muscles have become weaker. Here, we report a case of an intermediate form of collagen VI-related myopathy confirmed by next-generation sequencing. The girl presented morning headache, irritability, and aggressiveness, and because of these main symptoms, she was referred by the neurologist for respiratory evaluation. The result of spirometry was associated with hypoventilation shown during sleep studies, indicating the necessity to initiate home non-invasive ventilation (NIV) with immediate improvement in the symptoms. Neuromuscular disorders (NMDs) have a great impact on sleep, but only very few studies evaluating sleep quality in young patients with collagen VI-related myopathy have been described. Daytime symptoms of sleep-disordered breathing may include irritability, emotional lability, and poor attentiveness, but these can be overseen by the severity of other complex medical problems in patients with collagen VI-related myopathy. We underline the importance of the close monitoring of respiratory function, sleep evaluation, and decision making to support the NIV treatment of other collagen VI-related myopathy variant-specific patients. Early recognition of sleep disturbances and initiation of respiratory support can preserve or enhance the quality of life for patients and their caregivers. Routine screening for identification of emotional distress should be instituted in the clinical practice using validated psychological measures in a multidisciplinary approach with different intervention strategies for both patient and parent when necessary.
RESUMO
PURPOSE: Podocyte lesion is recently recognized as an early event in diabetic kidney disease (DKD) and is reflected by urinary (u) nephrin (Neph) shedding. Angiotensin II plays an important role in podocyte dysfunction of diabetes. Angiotensin converting enzyme 2 (ACE2) is the main ACE variant in podocytes and counteracts deleterious angiotensin II effects. We assessed for the first time the relation of uACE2 and uNeph in type 2 diabetes subjects. MATERIAL AND METHOD: Seventy-five type 2 diabetes patients were included in a transversal study. History, clinical and laboratory data, urinary albumin-to-creatinine ratio (uACR), and ELISA determination of uNeph and uACE2 were obtained. RESULTS: uNeph was 349.00 ± 133.42 pg/ml, and uACE2 was 45.50 (36.35-62.60) pg/ml. uNeph correlated to uACE2 (r = 0.44, p < 0.001) and to uACR (r = 0.25, p = 0.032). In multivariate regression, introducing parameters that are known to be related to DKD, uACE2 (p < 0.0001), LDL cholesterol (p = 0.02) and glycated hemoglobin (p = 0.03) remained significant predictors of uNeph. Normoalbuminuric patients had lower uNeph than patients with uACR > 30 mg/g (325.50 ± 135.45 vs 391.03 ± 121.40 pg/ml, p = 0.04); they also had a tendency versus lower uACE2 [41.40 (34.30-60.65) vs 52.57 (37.95-69.85) pg/ml, p = 0.06]. A cutoff for uNeph of 451.6 pg/ml was derived from the ROC curve analysis; uACE2 was the main determinant for uNeph being above or below this cutoff-OR = 1.09; 95 %CI (1.04-1.15), p = 0.001. Patients taking blockers of the renin angiotensin system had similar uNeph and uACE2. uNeph and uACE2 were not influenced by renal function. CONCLUSION: uNeph is significantly correlated to uACE2 and uACR in type 2 diabetes patients.