Every so often while she was a senior resident pursuing MD at the Banaras Hindu University (BHU) Institute of Medical Sciences, Sujata Sinha encountered patients with ?unexplained chronic anaemia? who would remain undiagnosed. Armed with a postgraduate degree, Sinha set up a pathological lab, the kind that looks at sugar levels in blood for diabetes or tests urine for pregnancy. But the puzzle that the patients with unexplained anaemia posed continued to rivet her. In between her bread-and-butter pathological work, she began detailed investigations of the blood samples of similar patients referred to her laboratory.

Now, Sinha and a team of collaborating scientists from the BHU may have jointly solved the puzzle. It may come as a reminder for doctors as well as the public that what the mind does not suspect, the eyes will not see. The researchers say a group of inherited blood disorders caused by abnormal haemoglobin may be distributed wider across northern Indian communities than previously believed. They have published their findings in the latest issue of Current Science, published by the Indian Academy of Sciences. ?Current assumptions about ethnic distribution of inherited blood disorders may need to be revised,? says Sinha.

Some geneticists, however, caution that because the study was based on patients referred by hospitals, it cannot be used to extrapolate prevalence of disorders in the general population. Medical studies in the past have thrown up special patterns in the distribution of genetic blood disorders that cause abnormal haemoglobin, one of which is beta thalassaemia. In northern India, for instance, beta thalassaemia appears concentrated among Punjabis and Sindhis. Another disorder, HbE, is found concentrated in West Bengal and the Northeast. Yet another disorder, HbS, is found primarily in tribal populations in central India.

The symptoms of disorders vary and depend on the exact abnormality. Some people with genetic mutations may only be ?carriers? without symptoms of the disease. Each of these blood disorders is caused by abnormal molecular structures of haemoglobin molecules. The abnormalities sharply reduce the lifespan of red blood cells. While a typical lifespan of a red blood cell is about 120 days, the lifespan of red blood cells in patients with these blood disorders may vary from 15 to 20 days. Anaemia is common in patients with severe symptoms of thalassaemia, and such patients require periodic blood transfusions.

Sinha analysed the blood samples of 120 patients with chronic anaemia and other symptoms referred to her by various doctors and hospitals in Varanasi and studied the ethnic distribution of the blood disorders that she detected. Eighty patients had beta thalassaemia, while the rest had a range of other abnormal haemoglobin disorders.

Unlike previous reports that showed thalassaemia concentrated among Punjabi and Sindhi populations, the study showed that 72 out of 80 patients with beta thalassaemia belonged to other population groups ? native Hindus and Muslims. The study also detected the blood disorder HbE, hitherto concentrated in West Bengal and the Northeast, among populations in eastern Uttar Pradesh.

The researchers also found the abnormal version of haemoglobin called HbS, until now widely believed to be found primarily among tribal populations in central India, among general Hindu castes in the Mirzapur-Sonebhadra region of Uttar Pradesh which borders a region of Madhya Pradesh with tribal populations known to have a high prevalence of HbS.

?Ethnic groups in India are not ?gene-tight? and over a period of time genes can percolate across ethnic groups helping the mutations move into different populations,? says Dr Partha Mazumdar, a human geneticist at the Indian Statistical Institute, Calcutta. Mazumdar says the only way to determine the prevalence of genetic disorders in the general community is through random screening of healthy people. The Varanasi study was based on sick patients referred by hospitals for diagnosis.

This introduces a referral bias so the study can?t be used to draw conclusions about prevalence in the general community.

?These findings highlight the need for screening the general population to estimate the prevalence of these disorders in this part of northern India,? says Professor Rajiva Raman, a geneticist in the department of zoology at the BHU and a coauthor of the study. The researchers say patients may have remained undiagnosed because doctors were influenced by prevailing ethnic biases and lack of diagnostic facilities.

Sinha recalls a 48-year old man who had been suffering from recurrent jaundice and weakness and had also been asked to undergo a liver biopsy. ?He had remained undiagnosed for years,? she says. During the study, he was found to have a single copy of the mutation for beta thalassaemia, but without symptoms. Unaware that he was a carrier, he had married and had five children. Four among them were also carriers.

Genetic screening for inherited blood disorders and prenatal diagnostic screening services are currently available at medical colleges in Lucknow and Calcutta. Mazumdar cautions that genetic screening of population for inherited blood disorders will be cost-effective only if the prevalence is indeed authenticated to be high.