Rare diseases

There are currently over 6,000 identified hereditary diseases, which include uncommon diagnoses that fall under the category of “rare diseases”, as well as somewhat more common hereditary diseases, such as hereditary cardiovascular diseases, neuromuscular diseases and cancers with a significantly increased hereditary risk.

In Sweden, a disease is defined as rare if it leads to a disability and occurs in less than 1 out of every 2,000 people. There are a large number of rare diseases so even if each disease may be rare in itself, there is a large number of people in Sweden that are affected (up to half a million). More than 70 percent of rare diseases have a genetic cause and many are chronic and life threatening and a majority of the diseases begin in childhood.

Since rare diseases are uncommon on an individual basis but large by number, it is very difficult for individual physicians to have a complete picture of all of these diseases. This means that many patients with rare diseases and other hereditary diseases have to wait a long time before they are diagnosed, meaning that they will also need to wait for a long time to receive treatment and follow-up. This is why a broad collaboration on a regional, national and international level is needed to improve care for these patients.

Technical development leading to better diagnostics

During the past few years, genetic methods that are built on so called next-generation sequencing (NGS) have become increasingly common in clinical diagnostics, which has enabled a shift in investigation strategy. Instead of analysing one gene at a time, so called gene panels are now used, where all known genes that may produce a clinical picture are included. As one of few places globally, analysis of an individual’s entire genetic material, so called whole genome sequencing, is now also an integrated part of healthcare across Sweden for rare diseases. More than 5,000 samples have already been analysed with the use of this technique, and during the next few years this number will be scaled up in order to meet the need that exists in this area.

The right diagnosis and faster treatment

When whole genome sequencing is integrated into healthcare, more people with rare diseases will receive a genetic explanation of their symptoms. This will lead to more patients receiving better medical treatment and follow-up. Since 2010, more than 230 drugs targeting rare diseases have been approved in the EU, but the number is continuously increasing.Whole genome sequencing already prevents premature death and severe disabilities for patients with treatable rare diseases.

Hereditary diseases in GMS

We want every patient in Sweden with a suspected hereditary disease to receive the most appropriate genetic test. Depending on what diagnosis is suspected this might be whole genome sequencing or a narrower analysis such as sequencing of the protein coding part of the genetic material (known as Whole Exome Sequencing). Within Genome Medicine Sweden (GMS) we are now aiming to coordinate gene sequencing in order to provide patients who have hereditary diseases, including rare diseases, the best diagnostics possible. We will do this through seven Genomic Medicine Centers (GMC) that are currently being built in all regions with university healthcare.

In addition to continued work to increase access to equitable diagnostics with whole genome sequencing, the working group for rare disease focuses primarily on finding ways to diagnose the approximately 60 percent of people with symptoms indicative of a rare disease but who remain undiagnosed even after whole genome sequencing. This is done through three major projects:

• Evaluate the addition of RNA sequencing as a complement to whole genome sequencing, which hopefully can further increase the diagnostic outcome. Some genetic variants are difficult to assess at the DNA level, and information on RNA can be important to draw correct conclusions.
• Evaluate the usefulness of long read sequencing, where the longer reads compared to routine clinical analyses can improve the possibility of mapping certain types of genetic abnormalities such as repeat expansion diseases, complex structural variants and for genes where the presence of pseudogenes makes interpretation difficult.
• Undiagnosed Diseases Network Sweden, focuses on children with undiagnosed rare syndromes with malformations and/or intellectual disabilities and investigates, among other things, how more individuals can be diagnosed by combining different methods of modern gene technology.

National coordination in rare diseases and other hereditary diseases

The team for rare diseases in GMS works actively within national networks such as the National Care Programme for Rare Disorders and the Swedish Society of Medical Genetics and Genomics (SFMG) and it also collaborates with the patient organisation Rare Diseases Sweden.

Co-chairs Rare diseases

Anna Lindstrand
Hans Ehrencrona
Lovisa Lovmar