Abstract
There are more than 150 different rare genetic kidney diseases. They can be classified according to diagnostic findings as (i) disorders of growth and structure, (ii) glomerular diseases, (iii) tubular, and (iv) metabolic diseases. In recent years, there has been a shift of paradigm in this field. Molecular testing has become more accessible, our understanding of the underlying pathophysiologic mechanisms of these diseases has evolved, and new therapeutic strategies have become more available. Therefore, the role of nephrologists has progressively shifted from a mere spectator to an active player, part of a multidisciplinary team in the diagnosis and treatment of these disorders. This article provides an overview of the recent advances in rare hereditary kidney disorders by discussing the genetic aspects, clinical manifestations, diagnostic, and therapeutic approaches of some of these disorders, named familial focal and segmental glomerulosclerosis, tuberous sclerosis complex, Fabry nephropathy, and MYH-9 related disorder.
Highlights
There is no consensual definition for rare diseases and, based upon the prevalence, the threshold varies across the globe
Some findings may alert the nephrologist to the necessity of genetic investigation: (i) young age of disease presentation; (ii) familial nephropathy background, such as pediatric or adult patients with familiar history of end stage renal disease (ESRD) or nephrotic syndrome; and (iii) children with focal segmental glomerulosclerosis (FSGS) not responding to conventional immunosuppressive treatment
Hereditary rare kidney diseases represent a great challenge in Nephrology practice
Summary
There is no consensual definition for rare diseases and, based upon the prevalence, the threshold varies across the globe. The onset of proteinuria is usually during the third and fourth decades of life and up to 60% of patients progress to ESRD in 10 years 15 Another autosomal dominant form of the disease was recently associated with mutations in INF2, a protein that regulates actin polymerization. Some findings may alert the nephrologist to the necessity of genetic investigation: (i) young age of disease presentation; (ii) familial nephropathy background, such as pediatric or adult patients with familiar history of ESRD or nephrotic syndrome; and (iii) children with FSGS not responding to conventional immunosuppressive treatment. Given that ESRD patients are considered a high-risk population, growing efforts have been made for screening Fabry disease in dialysis and transplant center This screening strategy may lead to the identification of index cases together with atrisk family members. If in one hand this approach is crucial to detect a commonly overlooked disease and to potentially allow earlier initiation of treatment of relatives, on the other hand, physicians should be aware it may increase the number of doubtful cases and misdiagnosis due to the detection of variants of unknown significance
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