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Advances in genetic testing, enable the identification of genetic causes even before symptoms appear, allowing for timely interventions and personalized treatment plans
Rare genetic disorders are often the result of mutations in a single gene, and many of these mutations can be inherited across generations
Rare diseases are life-altering medical conditions in an individual that are difficult to identify and diagnose because they seem to be heterogeneous in terms of signs and symptoms. Different countries classify rare diseases differently based on their own population, health care system, and resources, however, the standard definition given by the World Health Organisation for rare disease is any disease that affects fewer than 65 per 100,000 people.
Around 80% of rare diseases have a genetic cause, almost 70% of which present in childhood, about 95% lack approved treatments, and the average time for an accurate diagnosis is 4·8 years. In the past, these diseases often involved a lengthy diagnostic odyssey, but with the advent of genetic testing, healthcare providers can now pin point the genetic cause precisely and can provide early, targeted management and care. Dr Mahesh Hampe (MD, DNB), Senior Clinical Biochemist, MedGenome Labs shares all you need to know:
Genetic Testing for Early Diagnosis
Rare genetic disorders are often the result of mutations in a single gene, and many of these mutations can be inherited across generations. Conditions like cystic fibrosis, Huntington’s disease, and muscular dystrophies are examples of diseases caused by such single-gene mutations. Genetic testing plays a crucial role in identifying the risk of these disorders, often before symptoms appear. This early detection provides valuable insights that can inform personalized treatment strategies. In some cases, targeted therapies are available to address the underlying genetic defect, while in other situations, genetic data can guide supportive care decisions and help avoid ineffective treatments.
Genetic Testing Technologies
Advancements in genetic testing technologies, such as next-generation sequencing (NGS) and whole-genome sequencing (WGS), are transforming rare disease diagnosis by making genetic analysis faster, more thorough, and less expensive. While whole-genome sequencing examines the entire genetic code, whole-exome sequencing focuses specifically on the protein-coding regions, allowing for the identification of disease-causing mutations in known genes. Additionally, DNA microarrays can analyze millions of genetic variations from a single sample, providing a powerful tool to detect genetic variants that may contribute to disease risk.
Biochemical Genetics testing Technologies
American College of Medical Genetics (ACMG) have proposed a recommended Uniform Screening Panel (RUSP) which include those disorders which are most relevant in any Newborn screening (NBS) program. Inherited metabolic disorders recommended by ACMG like Congenital Adrenal hyperplasia (CAH), Cystic Fibrosis (CF) are performed using Time Resolved Fluoroimmunoassay (TRF) using dried blood spot (DBS). Other disorders like Biotinidase deficiency, Phenylketonuria or Galactosemia can be screened using simple Fluorometric enzyme assays using the same DBS sample. Fluorometric assays are more sensitive than ELISA and are quick methods of screening, and the results are available within 1-2 days so that the specific treatment can be initiated at the earliest. These biochemical assays (performed in DBS or leukocytes) can be used as adjunct to the diagnosis and treatment of lysosomal disorders (LSDs) like Gaucher’s disease, Pompe disease etc. and complement the molecular testing for establishing the diagnosis.
With technological advancement, Mass spectrometry has revolutionised the testing of inborn errors of metabolism (IEM) and we could perform more specific tests like Amino acids and acylcarnitine profile in the same DBS sample which confirm the IEMs like Maple Syrup Urine Disease (MSUD), Urea Cycle defects (UCD) and organic acidemia like methylmalonic acidemia (MMA). This testing is done on Liquid Chromatography Mass Spectrometry (LCMS) which are high throughput screening platforms that can analyse hundreds of samples in a day. Therefore, these tests are routinely performed for mass screening in many developed countries where the newborn screening (NBS) is a public health initiative.
Role of genetic counselling in rare diseases
Genetic counseling plays a crucial role in helping individuals navigate the challenges of living with a rare genetic condition. Genetic counselors provide support by explaining how these diseases impact the individual and the family, as well as offer guidance on genetic testing and related procedures.
Early diagnosis is key to improving patient outcomes and quality of life. Advances in genetic testing, enable the identification of genetic causes even before symptoms appear, allowing for timely interventions and personalized treatment plans. While challenges and ethical considerations remain, the ongoing progress in genetic technologies, coupled with the support of genetic counselors, brings hope for better diagnosis, management, and care of rare diseases, easing the burden on individuals, families, and healthcare systems.