Raising Awareness: Unveiling the Faces of 7 Rare Diseases in India
NextEdge Admin
18 Apr 2024
8 min 37 sec
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Pompe disease is a rare, multisystemic, autosomal recessive metabolic disorder which is caused by mutations in the acid α-glucosidase (GAA) gene. The GAA gene synthesizes acid alpha glucosidase, which is a lysosomal enzyme catalysing alpha 1,4 and alpha 1,6 linkages of lysosomal glycogen, mutations in this gene lead to a deficient or null product. GAA usually breaks glycogen into glucose. Mutations in the GAA gene cause abnormalities in the GAA enzyme, resulting in glycogen buildup in tissues, particularly cardiac and skeletal myocytes causing damage to tissue structure and function. Pompe disease is classified as early (infantile, classic) or late-onset (non-classic). Diagnosis is done by assessing the levels of GAA enzyme either in a blood sample or from a skin or muscle biopsy. Genetic testing is widely regarded as the most reliable method for establishing a definitive diagnosis. Enzyme replacement therapy (ERT) is at present the most effective treatment. Lysosomal glycogen buildup in cardiac and skeletal muscle is actively reduced by administering an analogous enzyme. Pombiliti and Opfolda a unique two-component therapy has also been approved for those adults living with late-onset Pompe disease and not improving on current therapies. Several gene therapies for Pompe disease are being developed.
Hirschsprung disease (HD) is a congenital disorder in which certain nerve cells are missing from the muscle layers of part of the large intestine. This causes severe constipation or blockage of the large intestine. Hirschsprung disease appears to have a dominant pattern of inheritance. It is caused by mutations in genes such as RET, EDNRB, and EDN3. Mutations in the RET gene, the primary genetic cause of Hirschsprung disease, disrupt the production of a signalling protein crucial for nerve cell development in the intestine. Nonfunctional RET protein due to mutations impairs nerve formation, causing intestinal complications characteristic of the disease. Abdominal x-ray, Contrast enema, Rectal biopsy are done for diagnosis of Hirschsprung disease. The usefulness of genetic testing after confirming Hirschsprung disease via biopsy is uncertain. Current guidelines suggest genetic testing for RET gene initially, followed by EDN3 and/or EDNRB if RET results are negative, especially in cases likely to be monogenic and non-syndromic. Stem cell-based therapies are being explored as these methods not only prevent the negative outcomes associated with conventional treatments but also strive to restore the normal development and function of the enteric nervous system.
Gaucher is an autosomal recessive disorder, and it is caused by mutations in GBA gene, causing deficiency of the enzyme glucocerebrosidase resulting in the accumulation of lipids specifically the glycolipid glucocerebroside, throughout the body especially within the bone marrow, spleen and liver leading to improper functioning. There are three types of Gaucher Disease (Type 1 ) most common and affect 90% of people, where person does not have enough platelets in the blood, (Type 2) affecting babies age of 3 to 6 months, (Type 3) Symptoms comprise skeletal issues, eye movement irregularities, progressively pronounced seizures, blood abnormalities, respiratory difficulties, and enlargement of the liver and spleen. The diagnosis of GD is based on the presence of inadequate glucocerebrosidase (glucosylceramidase) enzyme activity in peripheral blood leukocytes or other nucleated cells, or the identification of biallelic pathogenic mutations in GBA1 via molecular genetic testing. Molecular testing involves single gene testing or use of a multigene panel. Enzyme replacement therapy (ERT) and substrate reduction therapy (SRT) are two treatments currently available for Gaucher disease. Cerezyme (imiglucerase) by Sanofi Genzyme, VPRIV by Shire, and Elelyso (taliglucerase alfa) by Pfizer are U.S. Food and Drug Administration (FDA)-approved enzyme replacement therapies for Gaucher disease. Cerdelga (eliglustat) by Sanofi Genzyme is used as first-line treatment for patients with type 1 Gaucher disease. Zavesca (miglustat) by Actelion Pharmaceuticals is used for the treatment of patients with mild to moderate type 1 Gaucher disease who cannot be treated with enzyme replacement therapy. Gene therapy is being investigated as a possible treatment option for people with GD1.
Cystic fibrosis is an autosomal recessive genetic disorder of the body’s mucus gland, and it is caused by mutations in a gene called the cystic fibrosis transmembrane conductance regulator (CFTR). While there are many different types of CFTR mutations that can cause the disease, most of all people with CF have at least one F508del mutation. The CFTR gene provides instructions for the CFTR protein, which functions as a transmembrane cAMP-activated chloride channel. The change in CFTR protein results in thick mucus and elevated salt levels in sweat, leading to respiratory and digestive complications. Newborn screening makes it possible to detect the disease early in life. Genetic testing is done to check the carrier of mutated CFTR gene called carrier screening. Prenatal diagnostic testing is also done to check unborn baby for mutated CFTR gene if both parents are carriers. Although there isn’t a cure for cystic fibrosis currently, there are ways to manage the disease’ symptoms, prevent or minimise consequences. CFTR modulators have been approved by FDA for people with certain CFTR mutations such as Trikafta (elexacaftor/tezacaftor/ivacaftor), Symdeko (tezacaftor/ivacaftor), Orkambi (lumacaftor/ivacaftor), Kalydeco (ivacaftor). In addition to medication, getting the right nutrition is vital. In severe cases lung transplant might be recommended. Integration of gene therapies as potential treatment for cystic fibrosis is being investigated.
