Diagnosis and Treatment of Rare Disorders: Awareness Is the First Step

Medical Genetics is a speciality for diagnosis and treatment of rare diseases. Activities for awareness of these disorders are needed. Clinicians and patient support groups become more active around 28th February, the Rare Disease Day. We chose atypical hemolytic uremic syndrome (aHUS) for GenExpress in this issue for the same reason. aHUS is very rare with only few hundred cases occurring every year in a big country like India. The understanding of pathogenesis of aHUS has improved greatly over the last decade and availability of specific drug therapy has changed the outcome of this disease which can lead to chronic renal failure. It is extremely rare as compared to hemolytic uremic syndrome (HUS) and is associated with excess activation or dysregulation of the alternate pathway of complement, which is the part of the innate immune system. Genetic mutation with external trigger is required for the manifestations to appear. It is important to differentiate from HUS caused by bacterial toxins, other types of thrombotic thrombocytopenic purpuras and HUS secondary to malignancy, autoimmune disorders, etc. These diseases have similar clinical presentations and clinical suspicion and testing at lower threshold helps in the early diagnosis and institution of disease-specific therapy for genetic aHUS. Molecular diagnosis plays an important role. The articles in GenExpress in this issue cover the various aspects of aHUS including small experience from India. Similar to aHUS and HUS, other disorders with genetic and nongenetic etiologies with overlapping clinical features are seen; the examples being autoimmune and autoinflammatory disorders. Detection of causative pathogenic DNA variants is the basis for diagnosis of autoinflammatory disorders. Some autoinflammatory diseases have later onset and variable presentations, suggesting that some triggers are needed. On the other hand, autoimmune diseases have genetic susceptibility but do not follow the laws of Mendelian inheritance. Clinical features being similar, it is important to suspect monogenic disorders in patients with systemic lupus-like presentation. The boundaries between monogenic and multifactorial disorders are getting blurred. Knowledge of causative genetic variants helps in diagnosis and understanding of the pathogenesis helps in the development of drugs for genetic and nongenetic disorders. As next-generation diagnostics is improving diagnostic yield, the research in development of new therapies has also paced up. Not to miss the treatable disorder is our moto and Genetic Clinics continues to spread knowledge of recent developments in research and clinical practice of rare disorders. Exome sequencing-based testing has now become easily available in India and is being ordered by many clinicians. However, due to the limited data of benign and pathogenic variants in the Indian population, classification of variants is challenging. Submission of variants in patients to ClinVar and IndVar is very essential to decrease the numbers of variations of unknown significance. Genetic Clinics publishes case reports with novel causative variants and aims at documenting enhancing genotype and phenotypes of rare disorders, especially from India. This issue also has interesting case reports. If you have such unique cases or case series, please submit to Genetic Clinics. The first HACKATHON held recently (from February 3rd to 5th) at the Center for DNA Fingerprinting and Diagnostics, Hyderabad is a landmark scientific event in the history of rare diseases in India. More such collaborative efforts of experts are needed to help the patients and families of undiagnosed rare disorders mislabelled as cerebral palsy, birth asphyxia, idiopathic renal failure, etc., Be a champion for the cause of rare diseases as a clinician, scientist, medical geneticist, laboratory diagnostician or genetic counselor!