Gastrointestinal Manifestations and Low-FODMAP Protocol in a Cohort of Fabry Disease Adult Patients.

Fabry disease (FD) is an X-linked lysosomal disorder caused by α-galactosidase A enzyme deficiency. Gastrointestinal (GI) manifestations are reported in FD with a prevalence of about 50%, usually treated by Enzymatic Replacement Therapy (ERT) or oral treatment. Since FODMAPs (Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols) can be involved in GI manifestations and dysbiosis in FD patients, a low-FODMAP diet could represent an alternative adjunctive treatment in FD subjects, as well as being useful for reducing symptoms in Irritable Bowel Syndrome (IBS). We retrospectively assessed data from 36 adult FD patients followed at the Inherited Metabolic Rare Diseases Adult Centre of the University Hospital of Padova (mean age 47.6 ± 16.2 years). Patients were screened for GI symptoms by IBS severity score and Gastrointestinal Symptom Rating Scale (GSRS) questionnaires. In symptomatic patients, the low-FODMAP diet was proposed in order to improve GI manifestations; it consists of a phase of elimination of fermentable saccharides, succeeded by a gradual reintegration of the same. Severe or moderate GI symptoms were found in 61.1% of patients, with no correlation to the therapy in use, and significantly more severe in the classical form of FD. The protocol was completed by seven patients affected by severe GI manifestations, significantly higher than the others. The low-FODMAP diet significantly improved indigestion, diarrhoea, and constipation. This dietetic protocol seemed to have a positive impact on intestinal symptoms, by identifying and reducing the intake of the foods most related to the onset of disorders and improving the clinical manifestations. A low-FODMAP diet may be an effective alternative approach to improve intestinal manifestations and quality of life, and nutrition can play an important role in the multidisciplinary care of patients with FD.

Urine-Derived Epithelial Cells as a New Model to Study Renal Metabolic Phenotypes of Patients with Glycogen Storage Disease 1a.

Glycogen storage diseases (GSDs) represent a model of pathological accumulation of glycogen disease in the kidney that, in animal models, results in nephropathy due to abnormal autophagy and mitochondrial function. Patients with Glycogen Storage Disease 1a (GSD1a) accumulate glycogen in the kidneys and suffer a disease resembling diabetic nephropathy that can progress to renal failure. In this study, we addressed whether urine-derived epithelial cells (URECs) from patients with GSD1a maintain their biological features, and whether they can be used as a model to study the renal and metabolic phenotypes of this genetic condition. Studies were performed on cells extracted from urine samples of GSD1a and healthy subjects. URECs were characterized after the fourth passage by transmission electron microscopy and immunofluorescence. Reactive oxygen species (ROS), at different glucose concentrations, were measured by fluorescent staining. We cultured URECs from three patients with GSD1a and three healthy controls. At the fourth passage, URECs from GSD1a patients maintained their massive glycogen content. GSD1a and control cells showed the ciliary structures of renal tubular epithelium and the expression of epithelial (E-cadherin) and renal tubular cells (aquaporin 1 and 2) markers. Moreover, URECs from both groups responded to changes in glucose concentrations by modulating ROS levels. GSD1a cells were featured by a specific response to the low glucose stimulus, which is the condition that more resembles the metabolic derangement of patients with GSD1a. Through this study, we demonstrated that URECs might represent a promising experimental model to study the molecular mechanisms leading to renal damage in GSD1a, due to pathological glycogen storage.

High prolactin levels in dihydropteridine reductase deficiency: A sign of therapy failure or additional pathology?

We report the case of a 22-year-old man with a diagnosis of dihydropteridine reductase (DHPR) deficiency who progressively developed movement disorders and epilepsy. Despite L-Dopa supplementation the patient continued to show high prolactin levels, with a discrepancy between the neurological clinical picture and the hormonal biochemical levels. For this reason, other potential causes were ruled out by performing a cerebral magnetic resonance imaging, which demonstrated a solid lesion in the pituitary gland strongly suggestive of a prolactinoma. As the association between metabolic disorders affecting biogenic amine synthesis and prolactinoma has not been previously reported in humans, this report suggests that a critical evaluation of the use of prolactin as a guide for therapy dosage should be made in patients with DHPR deficiency disorders.

[Renal biopsy in the lateral position in high risk patients: an opportunity to take advantage of]. / La biopsia renale in decubito laterale nei pazienti complessi: una possibilità da sfruttare.

Percutaneous ultrasound-guided renal biopsy (RB) is the gold standard for diagnosis of renal diseases. The standard procedure involves biopsy in the prone position (PP) for the native kidneys. In high risk patients, transjugular and laparoscopic RB have been proposed. In patients suffering from obesity or respiratory diseases, the RB of the native kidney in the supine anterolateral position (SALP) represents an alternative to these invasive and expensive methods. We illustrate the technique of execution of RB in the lateral position (LP) on native kidneys. The procedure is safe, effective and has reduced the path travelled by the needle biopsy compared with PP and SALP.

Pro-inflammatory monocyte-macrophage polarization imbalance in human hypercholesterolemia and atherosclerosis.

Monocyte-macrophages (MoMas) play a major role in atherosclerosis. In mice, hypercholesterolemia increases pro-inflammatory monocytes that promote plaque growth, but whether this is true also in humans in unknown. We herein analyzed monocyte subsets and MoMa phenotypes in familiar (FH, n = 22) and non-familiar (NFH, n = 20) hypercholesterolemic compared with normocholesterolemic (CTRL, n = 20) patients. We found that FH and NFH had higher circulating pro-inflammatory CD68(+)CCR2(+) M1 MoMas than CTRL, while anti-inflammatory CX3CR1(+)CD163(+)/CD206(+) M2 MoMas were reduced only in NFH. As a result, the M1/M2 polarization balance was increased in FH and, more markedly in NFH. M1 MoMas and the M1/M2 polarization ratio were directly correlated to pre-treatment LDL cholesterol levels and strongly associated with the presence of atherosclerotic plaques. In conclusion, we show for the first time that human hypercholesterolemia is associated with a pro-inflammatory imbalance of circulating monocytic cells, which can predispose to the development of atherosclerosis.

Common hepatic lipase gene promoter variant predicts the degree of neointima formation after carotid endarterectomy: impact of plaque composition and lipoprotein phenotype.

BACKGROUND: The common -514 C-T promoter polymorphism of the hepatic lipase gene (LIPC) and the cholesteryl ester transfer protein (CETP) gene TaqIB polymorphism affect atherogenesis. We investigated the potential relationship between these polymorphisms and the maximum-intima-media thickness (M-IMT) after carotid endarterectomy. METHODS: The LIPC and CETP genotypes were determined by PCR in 68 patients undergoing endarterectomy. Plaque specimens were analysed for cell composition by immunocytochemistry. Six month after surgery the M-IMT of the revascularized vessel was assessed by B-mode ultrasonography. RESULTS: The CC carriers had denser LDL particles (p<0.0005), an abundance of macrophages (p<0.0005), fewer SMCs in the carotid plaque (p<0.0005), and higher prevalence of cerebrovascular events (72% versus 28%, p=0.002) compared to CT/TT carriers. After endarterectomy, CC carriers showed a lower M-IMT than the CT/TT group (1.36 mm versus 1.76 mm, p=0.04). No association between the CETP polymorphism and either carotid plaque cellular composition or M-IMT was observed. In a multivariate analysis, M-IMT was associated with plaque cell composition (macrophages, r=-0.39; SMC, r=0.44; p<0.005 for both) but not with pre-operative LDL-C, HDL-C, triglycerides, or LDL density. CONCLUSIONS: The LIPC promoter -514 C-T polymorphism is associated with a significantly reduced development of neointima after surgery. This effect seems to be mediated by scarcity of SMC in the plaque of CC carriers who display an excess prevalence of cerebrovascular events prior endarterectomy but are at low risk for restenosis. The pre-operative lipid phenotype plays a marginal role in the neointima formation.