Aicardi-Goutières syndrome (AGS) is a rare genetic disorder involving the central nervous system and autoimmune abnormalities, leading to severe intellectual and physical disability with poor prognosis. AGS has a phenotype similar to intrauterine viral infection, which often leads to delays in genetic counseling. In this study, a case with a prenatal diagnosis of AGS is reported. The first fetal ultrasound detects bilateral lateral ventricle cystic structures, and fetal MRI is performed to identify other signs. The right parietal lobe signal shows cerebral white matter abnormalities, and fetal brain development level is lower than that of normal fetuses of the same gestational age. Whole-exome sequencing is performed and the final comprehensive diagnosis is AGS1. In this article, also the previous literature for possible phenotypes in the fetus is preformed and the conclusion that microcephaly and intrauterine growth retardation may be the first and most important markers of the intrauterine phenotype of AGS is made. Read the full article here.
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An unusual case of Takayasu arteritis presenting as acute myocardial infarction and ischaemic stroke
Takayasu’s arteritis (TA) is well-known yet rare disorder, defined as a chronic large vessel vasculitis mainly involving the aorta and its major branches. A case of 51-year-old female patient who is admitted at the Clinic of Nephrology and Clinical Immunology is presented. During hospitalization, a sudden onset of intense chest pain occurres, followed by a development of heart failure to the level of cardiogenic shock. Electrocardiography shows signs of ST-elevated myocardial infarction (STEMI) of the anterior wall, and an increase in cardiospecific enzymes. CT angiography indicated an occlusion of the left common carotid artery (ACC), subclavian and axillary arteries as well as a penetrating aortic ulcer localized infrarenal. In the further course of treatment, left-sided weakness of the body is registered. Head CT scan shows an acute ischemic lesion high parietal on the right, as well as a chronic ischemic lesion on the front right. Final diagnosis of Takayasu arteritis is established and corticosteroids is included in the therapy. This disease should be considered in female patients who present with chronic inflammation and acute coronary syndrome. Read the full article here.
Huntington’s disease (HD) is a rare neurodegenerative disorder with no disease modifying therapeutics. HD is characterized by extensive neuronal loss and is caused by the inherited expansion of the huntingtin (HTT) gene that encodes a toxic protein. Current HD therapeutics only offer symptomatic relief. Infact, Food and Drug Administration (FDA) approved two synthetic small-molecule inhibitors, tetrabenazine and deutetrabenazine, for managing HD chorea and various other diseases in clinical trials. Therefore, the landscape of drug discovery programs for HD is evolving. Likewise, numerous natural products are being evaluated at different stages of clinical development and have shown the potential to ameliorate HD pathology. The inherent anti-inflammatory and antioxidant properties of natural products mitigate the mHTT-induced oxidative stress and neuroinflammation, improve mitochondrial functions, and augment the anti-apoptotic and pro-autophagic mechanisms for increased survival of neurons in HD. This article discusses HD pathogenesis and summarizes the anti-HD clinical and pre-clinical natural products, focusing on their therapeutic effects and neuroprotective mechanisms. Read the full article here.
Prader-Willi syndrome (PWS) is a rare and complex genetic disease, with numerous implications on metabolic, endocrine, neuropsychomotor systems, and with behavioral and intellectual disorders. Rare disease patient registries are important scientific tools to collect clinical and epidemiologic data, to assess the clinical management including the diagnostic delay, to improve patients’ care and to foster research to identify new therapeutic solutions. The European Union has recommends the implementation and use of registries and databases. The main aims of this paper are to describe the process of setting up the Italian PWS register, and to illustrate our preliminary results. The Italian PWS registry was established in 2019 with the aims to describe the natural history of the disease, to determine clinical effectiveness of health care services, to measure and monitor quality of care of patients. Information from six different variables are included and collected into this registry: demographics, diagnosis and genetics, patient status, therapy, quality of life and mortality. The analyses of these six variables allowed to highlight important clinical aspects and natural history of PWS useful to inform future actions to be taken by national health care services and health professionals. Read the full article here.
Urbach-Wiethe disease is an extremely rare genetically-based syndrome which usually leads to dermatological and neurological changes. Neurologically, the amygdaloid region is primarily bilaterally affected. Therefore, several functions modulated by the amygdala are changed in patients with Urbach-Wiethe disease. As the neurological alterations evolve only gradually, it is particularly important to determine the cognitive and brain status of a juvenile. In this case a patient is seen briefly at age 9 and tested neuropsychologically at age 19; furthermore, computer tomography and magnetic resonance imaging of his head is done. There are no important abnormalities in the brain, which is unusual in the light of previous data from other patients. On the cognitive level, the patient is generally within normal limits. However, he has mild problems in attention and concentration, and more prominent problems in emotional processing domain, and in personality dimensions. It is concluded that amygdala calcifications in Urbach-Wiethe disease take place progressively-possibly underpinned by genetic and gender variables; this can subsequently allow psychosocial-social factors (such a proper education and socialization) and biological factors (compensatory neuroplasticity) to retard and diminish the development of socio-emotional and cognitive deteriorations. Read the full article here.
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). Data from 36 adult FD patients followed at the Inherited Metabolic Rare Diseases Adult Centre of the University Hospital of Padova is retrospectively assessed. In symptomatic patients, the low-FODMAP diet is proposed in order to improve GI manifestations. Severe or moderate GI symptoms are to be 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 low-FODMAP diet significantly improves indigestion, diarrhoea, and constipation. This dietetic protocol seems 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. Read the full article here.
Addison’s disease which is due to dysfunction of the adrenal gland, with abnormal secretion of glucocorticoids and mineralocorticoids, is rare. By inducing inflammation and disorders of water and electrolyte metabolism, Addison’s disease may accelerate progression of co-existed cardiovascular diseases. Addison’s disease combined with cardiovascular disease is infrequent, only 10 cases in the literature. In this case a 51-year-old male patient with unstable angina pectoris and hypotension is reported. Changes on coronary angiography within 2 years suggest rapid progression of coronary artery disease in a patient with low cardiovascular risk. An additional clue of skin hyperpigmentation, fatigue and further examination confirm the diagnosis of Addison’s disease caused by adrenal tuberculosis. After hormone replacement treatment, the frequency and severity of the angina pectoris are alleviated significantly, as were hypotension, hyperpigmentation and fatigue. The combination of Addison’s disease and coronary artery disease in one patient is rare. Addison’s disease can induce inflammation and disorders of water and electrolyte metabolism, which may further accelerate the course of coronary artery disease. Meanwhile, the hypotension in Addison’s disease may affect the coronary blood flow, which may result in an increased susceptibility to unstable angina in the presence of coronary stenosis. Read the full article here.
Thrombotic thrombocytopenic purpura (TTP) is considered to be a rare cause of ischemic stroke (IS). A case of a newly diagnosed patient with acquired immune-mediated TTP (iTTP) is reported, in whom two IS events developed during 48 h. A 59-year-old diabetic male is presented to the hospital 24 h after symptoms onset, including left hemiparesis, dysarthria, and decreased consciousness. A brain CT scan is performed with the suspicion of acute IS, indicating infarct lesions in the right middle cerebral artery (MCA) territory. The patient is not eligible for thrombolytic therapy due to admission delay. Over the next 24 h, the patient’s neurological condition deteriorates, and the second brain CT scan shows new ischemic lesions. Initial laboratory evaluation indicates thrombocytopenia without evidence of anemia. However, in the following days, thrombocytopenia progresses, microangiopathic hemolytic anemia (MAHA) develops and the diagnosis of iTTP is confirmed. The patient undergoes plasma exchange, pulse IV methylprednisolone and Rituximab is also added due to the refractory course of the disease. After a prolonged hospital course, he has considerable neurologic recovery and is discharged. Thrombotic thrombocytopenic purpura should be considered in any patient presenting with IS and having thrombocytopenia or anemia without other symptoms of TTP. Read the full article here.
Multisystem inflammatory syndrome after COVID-19 in childhood and genetic predisposition
Multisystem inflammatory syndrome in children (MIS-C) occurs 3-6 weeks after COVID-19. Clinical symptoms of MIS-C include fever, rash, conjunctivitis, gastrointestinal or other organ symptoms, including cardiac dysfunction. The incidence of MIS-C is 2 / 100 000 children with SARS-CoV-2.It is crucial to know why MIS-C is not observed in all children after COVID-19. To date, several candidate genes associated with the development of MIS-C have been proposed as predisposing factors. The small number of proposed genes is probably also related to the relatively small size of the cohorts of children with MIS-C. A large number of studies related to genetic predisposition to this condition are not yet available. This review describes the studies that have been published up to date. The full text of the article can be read here.
The aim of this article is to evaluate cost-effectiveness of combination therapy with SSA (somatostatin analogue) + pegvisomant compared to monotherapy with SSA in patients with acromegaly in Bulgaria. The study is prospective as data on the effectiveness (change in insulin-like growth factor 1 (IGF-1) levels (nmol/l),) among patients with acromegaly treated at “Acad. I. Penchev” Hospital. The incremental cost-effectiveness ratio (ICER) was 15 651.74 BGN for additional 1 nmol/l reduction in IGF-1, which represents the additional cost to be paid per 1 unit incremental outcome for treatment with the combination therapy. The ICER was below the upper cost-effectiveness threshold of 3 times the gross domestic product per capita according to a model developed by the World Health Organization. 30% reduction in the cost of SSA+Pegvisomant was accompanied by the most significant impact on ICER. The probability SSA+Pegvisomant therapy to be cost-effective is 61.4% when the willingness to pay threshold is 35 230.52 BGN additional cost per unit of incremental improvement. The full text of the article can be read here.