From Genometo Syndrome: The Rare Disease Riddle

By Rasika, Mapmygenome

A is for Albinism, B is for Bloom’s, C is for Cat-eye… for almost every letter in the English alphabet, there is a rare disease which affects less than 1% of the population. How are they caused? The answer can be found a little closer to home, literally. As diverse as they are in their complex symptoms, astonishing features and shocking abnormalities, these stories have a common beginning – inside the cell’s nucleus, rooted in DNA.

Facts about disease – some rare truths

  • Heredity is very real – There are more than 7000 known rare diseases in the world. Most of the rare diseases in the world are inherited and are caused by genetic changes. (Note : Some cancer syndromes and infectious diseases are not hereditary)
  • Bases in the bassinet – Almost half of the rare diseases manifest early, in very young children. Gene (and chromosome) alterations disrupt innate biological developments which could be physical, metabolic or neurological. For example, a single base (letter) change in important regions of DNA, can be a grave concern for doctors.
  • Guessing is no child’s play – Two children could suffer from the same condition, yet be distinct in profile, clinically. Barring a few obvious symptoms, rare diseases vary a lot between patients. Misdiagnosis is quite common in such cases, putting the affected individual at a high risk for severe disability.
  • Remembering our roots – Certain mutations occur in high frequencies in their founder populations (eg., Ashkenazi Jews, Amish, South Africa etc). The corresponding disorders have an increased occurrence in those populations, due to consanguinity. Marriages between first-degree relatives are linked with a high risk for autosomal recessive disease, wherein both the parents pass on a faulty gene to their child. Here’s a fascinating example – The Blue Fugates of Kentucky represent a family with methemoglobinemia. The condition causes a blue coloring in the skin. Genetic anomaly (in the CYB5R3 gene) has been carried forward, due to inbreeding over 6-7 generations.
  • Discovering the magic pill – Given their extremely low prevalence rates, rare diseases were tough to manage, a few decades ago. “Orphan” drugs (specialized drugs used to treat rare disease) had to be developed by pharmaceutical firms and made accessible to patients, globally. This was implemented through certain regulations such as those of the European Union (EU) and the Orphan Drug Act of 1983 (USA).
  • Eccentric examples – Quadruped behaviour (walking on all fours), hair growth which resembles a werewolf, progeria (Bachchan Sr got that right), smelling like fish ALL the time, etc., are found in people with super-rare genetic mutations, some of which could be fatal.

Genomics in healthcare – The final piece in the puzzle?

The discovery of genes and inheritance (thank you, Mendel!) paved way for tremendous development in medicine. Assessment of patients suffering from rare diseases is a multi-tier process which involves clinical evaluation, identification of known (or unknown) symptoms, detailed study of family history, risk stratification, potential therapeutic strategies and management regimes. Genetic studies, when executed as a part of this procedure, provides valuable clues which lead to diagnostic confirmation. But this protocol is easier explained than done.

Genomics can help overcome many challenges faced by the medical community, such as those mentioned below.

  • A lot of times, first-hand information about the disease is received only upon onset. This could happen in a hospital ward, either during childbirth (newborns) or much after. Awareness drive in families, access to screening options and guidance support need to be practised in institute/hospital. The establishment of more genetic analysis units, is one such step, towards better healthcare.
  • Some conditions are so rare that there are ➢ Medical data (including genetic etiology) of every disease needs to be available with clinicians and counselors alike.
  • Molecular changes such as chromosomal rearrangements, gene duplications, deletions, protein alterations, etc., are associated with serious deformities, blood disorders and metabolic deficiencies which could be irreversible. Carrier status (presence/absence of such defects) followed by informed decision making (a.k.a reproductive planning) reduces disease burden in affected families.

What determines a child’s fate, once brought into this world? Maybe it is the hand that rocks the cradle (i.e, the all-powerful mother’s love) – but science disagrees. Both the parents pass on an everlasting legacy to the child, which is imprinted in every cell. Is it safe to say that life’s journey is predetermined? We will leave that discussion to another time!

Please read the original article on Mapmygenome’s blog at

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