Unusual Cause of Thrombocytopenia and Renal Failure in a 14-Year-Old Boy (MYH9-Associated Disorders).

MYH9-associated disorders represent rare group of autosomal dominant diseases and are caused by pathogenic mutations in the MYH9 gene. Clinically, they are represented by macro-platelet-thrombocytopenia, various degrees of renal dysfunction, hearing loss, and early onset cataracts. We describe the case of 14-year-old boy in medical follow-up from birth for thrombocytopenia. Systolic hypertension and nephrotic proteinuria were detected at preventive health check. Renal biopsy revealed sing of segmental glomerulosclerosis. Dialysis treatment was needed. Before transplantation due to the finding of chronic tonsillitis with positive bacterial capture in the culture examination, tonsillectomy was indicated. Postoperative period was complicated with arterial post-tonsillectomy hemorrhage. Six months after tonsillectomy, the patient underwent primary deceased-donor kidney transplantation without complication. Blood platelets showed fluctuating character in the zone of severe thrombocytopenia. However, no signs of bleeding were present. Three months after successful transplantation gene sequencing of whole exon was performed. The presence of the variant c.2105G>A [p.(Arg702HIS)] in exon 17 of the MYH9 gene has been detected. The variant c.2105G>A may be clinically manifested by progressive proteinuria with rapid deterioration of renal function. This case is an example of the delayed diagnosis of rare disease and highlights the usefulness of genetic testing.

Sensenbrenner Syndrome Presenting with Severe Anorexia, Failure to Thrive, Chronic Kidney Disease and Angel-Shaped Middle Phalanges in Two Siblings.

Sensenbrenner syndrome is a very rare autosomal recessive disorder caused by variants in genes involved in the functional development of primary cilia. Typical clinical manifestations include craniofacial and skeletal abnormalities, hence the alternative name cranioectodermal dysplasia. Chronic kidney disease due to progressive tubulointerstitial nephritis (nephronophthisis) has been described in these patients. The authors present 2siblings with severe anorexia, failure to thrive, chronic kidney disease, and angel-shaped middle phalanges. Two previously described variants p.(Leu641*) and p.(Asp841Val) were identified in the WDR35 gene which is most commonly affected in this condition. Analysis of all coding exons of the GDF5 gene was normal. This is the first report of Sensenbrenner syndrome presenting with severe anorexia and failure to thrive at early age. Angel-shaped middle phalanges in the absence of the GDF5 variant may represent an overlapping phenotypic manifestation of ciliopathy.

Changes of Motile Ciliary Phenotype in Patients with Primary Ciliopathies.

Primary ciliopathies are a group of disorders associated with abnormal formation and function of primary cilia. Many cilia-associated proteins found in primary cilia are also present in motile cilia. Such proteins are important for the ciliary base, such as the transition zone or basal bodies, and the intraflagellar transport. Their exact role in the respiratory motile cilia is unsettled. In this prospective clinical single-center study, we investigated the hypothesis that these proteins regulate the function of motile cilia. We addressed the issue by defining the motile cilia beat frequency in the respiratory tract of patients with primary ciliopathies accompanied by chronic kidney disease and comparing it in those without kidney involvement. Ciliary beat frequency in the nasal mucosa samples was evaluated by the ciliary analysis software LabVIEW. Both children and their parents with primary ciliopathies and kidney involvement had significantly lower median airway ciliary beat frequencies than those without kidney involvement who have normal ciliary motility. Further, the ciliary beat frequency is inversely associated with the serum creatinine level. These findings strongly suggest that kidney involvement in patients with primary ciliopathy may underlie the development of motile cilia dysfunction in the respiratory tract, potentially increasing respiratory morbidity.

Immune Parameters and COVID-19 Infection - Associations With Clinical Severity and Disease Prognosis.

Severe acute respiratory syndrome caused by a novel 2019 coronavirus (SARS-CoV2) represents one of the most studied infectious diseases of today. The number of scientific reports and publications increases exponentially day by day. While the majority of infected subjects are asymptomatic or show mild symptoms, there is an important proportion of patients who requires hospitalization and, sometimes, intensive care. Immune response to novel coronavirus is complex, involves both innate and adaptive immunity, and is biphasic. Significant differences were observed when comparing severe and non-severe patients. Analysis of the reported results from clinical trials clearly show an involvement of specific cellular immunity (predominantly leucopenia, decreased counts of CD3+, CD4+, and CD8+ T lymphocytes, changes of T cell compartment) and the so-called cytokine storm, which is associated with worsening of symptoms and the promotion of lung damage. An interesting finding regarding eosinopenia that can have both diagnostic and prognostic value is reported by some authors. Examination of selected immune parameters could help to identify severe patients with the risk of unfavorable course of the disease, predict the prognosis and recognize improvement in the clinical status. Moreover, detailed analysis of the immune changes could help to select novel prospective therapeutic strategies.

Nephronophthisis type I, left ventricular non-compaction cardiomyopathy and reduced cilia motility-atypical manifestations of one disease.

Nephronophthisis, an autosomal recessive cystic kidney disease, represents genetically heterogenous group of diseases that lead to end-stage kidney disease in children and young adults. The typical clinical manifestations are polyuria, enuresis and growth failure. Left ventricular non-compaction cardiomyopathy is a rare form of cardiomyopathy, is determined by the disturbance of embryogenesis of the endocardium and myocardium. Primary ciliary dyskinesia is a genetically heterogeneous recessive disorder of motile cilia characterised by chronic lung disease and nonpulmonary manifestations, usually situs inversus. Almost no information is available in the literature about the association between nephronophthisis, left ventricular non-compaction cardiomyopathy and reduced cilia motility. The authors present the case of 17 year-old girl with left ventricular non-compaction cardiomyopathy, non-specific lung nodules and end-stage kidney disease. A genetic examination confirmed only diagnosis of nephronophthisis type I. Cardiac magnetic resonance imaging confirmed left ventricular non-compaction cardiomyopathy. Cilia motility was reduced in nasal mucosa samples. Are all clinical manifestations part of one disease? This report points to a variety of clinical manifestations of ciliopathy and aims to understand the individual relationships.