A 14-year-long study on prenatal diagnosis (PND) of rare genetic disorders, conducted by a leading Ahmedabad-based institute and funded by the Central government’s department of biotechnology, for over 1,700 samples from 10 states and two Union Territories has found that more than a quarter of the foetuses suffered from “genetic anomalies”, and 7.7% had “other rare genetic disorders”.
The study, conducted by the FRIGE Institute of Human Genetics, Ahmedabad, from 2008 to 2022, from 12 tertiary healthcare centres and published earlier this week in the Orphanet Journal of Rare Diseases, showed, that out of 1,738 prenatal cases, 752 (43.27%) foetal samples were ‘Normal’ and showed no signs of genetic diseases. But in 519 (29.86%) cases, the foetus was identified as a ‘carrier’ of the disease, while in 467 (26.87%) cases, the results found that the child would be born suffering from a genetic disorder. About 75% of the samples were from Gujarat.
Of the 467 cases, 406 concerned those of autosomal recessive (AR) disorder with examples including Cystic Fibrosis, Sickle Cell Anaemia, Tay-Sachs Disease, and Wilson’s Disease. In 21 cases, the sample results exhibited an autosomal dominant (AD) mode of inheritance, such as Huntington’s Disease. Forty of the cases were with X-linked inheritance patterns, examples including Haemophilia. The study only focussed on diseases with molecular or biochemical genetic aetiology and did not include cases with chromosomal abnormalities identified through PND.
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Corresponding author of the paper, Dr Harsh Sheth of the FRIGE (Foundation for Research in Genetics and Endocrinology) Institute of Human Genetics said, “Rare genetic disorders are increasingly diagnosed due to advancing genetic technology, whilst treatment for them is challenging. Especially in low-middle income countries like India, providing treatment that costs crores of rupees makes it a significant economic barrier to accessing life-saving treatment. Therefore, (identifying) rare disease by prenatal diagnosis is a way forward to reduce the overall burden.”
According to Dr Sheth, of the 467 cases in which the foetus was found suffering from disease, roughly three/fourth were from Gujarat, in line with the sample size. Most common diseases were thalassemia, sickle cell anaemia, Spinal Muscular Atrophy (SMA), Duchenne Muscular Dystrophy (DMD) and lysosomal storage disorders, in that order. A significant chunk of sickle cell anaemia cases came from the eastern belt of Gujarat, especially from Tapi district.
Early diagnosis facilitated timely medical information and provided options for prevention, such as medical termination of pregnancy (MTP) in affected cases after genetic counselling. For all foetuses with a confirmed diagnosis for a genetic disorder, the clinical management involved a multidisciplinary approach.
The core research team included foetal medicine experts, clinical geneticists, neonatologists, and genetic counsellors. The potential natural course of the disease, available treatment options, associated costs, supportive care options in cases where treatment is not available, and existing government schemes were discussed in detail with the families, said the paper.
Said Dr Sheth, “We undertook one of the largest epidemiological studies in India to understand the role of prenatal testing in disease prevention, and (identify) which diseases are the most commonly detected. Undertaking a study like this helps the policy makers develop targeted disease prevention interventions, both at national and community level. It also helps the research community develop focus on diseases that are most common, so that they can work towards the development of affordable, accessible, and indigenous therapeutics, for them.”
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Majority of the patients covered by the study, which has nearly a dozen contributors, were from the western states — Gujarat, Maharashtra and Rajasthan. One of the reasons for this was the institute’s location in Gujarat “thereby, making it easier for patients from these states to travel for pre- and post-test genetic counselling, and prenatal testing,” said Dr Sheth. “India, while advancing in urban areas, faces challenges in expanding these services to rural populations and ensuring affordability for economically disadvantaged groups,” he added.
Due to lack of awareness not just among the public but also doctors, it is rare to see people seeking genetic testing before marriage, before conceiving, and unless they have one child who has suffered or had died due to a genetic disorder.
Dr Sheth, who is also the founder of the institute, said, “Impetus must be given to awareness regarding prenatal diagnosis, carrier screening and family counselling to make sure that two carriers of the same rare diseases genes do not marry and if they do, then go for prenatal diagnosis to make an informed choice.”
However, in many cases, genetic testing may not be carried out even if there is ample medical cause, due to the cost of the tests which can be between Rs 18,000 and Rs 24,000.
While Gujarat accounted for 73.42% of the samples, Maharashtra’s share was 19.2% and Rajasthan’s 3.62%. The rest of the states included Karnataka (1.38%), Kerala and Andhra Pradesh (0.46%), Madhya Pradesh (0.29%), Telangana (0.12%), Tamil Nadu and Uttar Pradesh (0.06%), and the Union Territories of Chandigarh (0.69%) and Delhi (0.23%). Therefore, the overall impact of the PND on pregnancy couldn’t be concluded in the present study.
The study found that in five cases, only a single heterozygous variant was detected in a gene associated with an autosomal recessive disorder. Among the limitations of the study was that although the parents were given extensive post-test genetic counselling, they were lost to follow-up and their pregnancy outcome couldn’t be recorded.
In August 2024, another study — The Burden of Rare Genetic Disorders in India: Twenty-two Years’ Experience of a Tertiary Centre — was also published from 40 centres across India and contributions from more than 50 authors, with data from 2000 to 2022, in Orphanet Journal of Rare Diseases.
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The authors claimed this was the very first estimate of the burden of rare genetic disorders in India, encompassing 22 years of data consisting of 3,294 patients suffering from 305 rare diseases under the umbrella of 14 disease groups.
The highest number of disorders — 149 or 48.9% — fell in the neuromuscular and neurodevelopmental group (NMND). This was followed by inborn errors of metabolism (IEM) group, which accounted for 47 of 305 diseases, accounting for 15% of the total.
Substantially, a majority of the patients in the cohort, 1,992 out of 3,294 (61%), suffered from the IEM group. Further, of these 1,992 patients, the maximum number — 224 or 11.2% of patients — suffered from Gaucher disease.
The most common rare diseases under the umbrella of the NMND group affecting 885 patients was DMD that had affected a total of 295 patients (32.9%), while 242 (27.3%) suffered from trinucleotide repeat expansion disorders (TRDs), and 141 patients (15.9%) were diagnosed with spinal muscular atrophy (SMA).
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Under the haematological group of 149 patients, 120 (80.5%) accounted for Thalassemia in the 2024 study. Of the 75 patients in the pulmonary group of diseases, cystic fibrosis accounted for the maximum cases at 74 patients (98.7%).
Almost half of all diagnosed cases in this study — 1,601 (48.6%) — were from Gujarat. This was followed by 25% cases from Maharashtra.