A team of scientists has solved a medical mystery by discovering the causes of the kidney failure that triggered a wave of infant deaths in the 1930s and 1940s. It all started in the early 1900s when more than 80% of children in industrialized Europe The US and North America were affected by rickets, a disorder that is due to a lack of calcium and vitamin D and that causes pain in the bones, which soften, weaken and deform, and prevents children from growing and developing normally .
Because sunlight prevents rickets, the decision was made to fortify certain foods—bread, milk, cereals, and margarine—with vitamin D, which allowed this disease to be nearly eradicated in the 1930s. outbreaks of vitamin D poisoning in infants caused many European countries to ban this fortification in the 1950s. “Foods such as dairy products had been fortified with vitamin D, but it led to the deaths of several babies and was eventually banned in many countries, except for breakfast cereals and margarine,” explained lead researcher Dr Darrell Green, from the University of East Anglia Norwich Medical School.
There is a disorder that prevents adequate metabolization of vitamin D, which causes an accumulation of calcium in the blood that causes the formation of kidney stones and the deterioration of the kidneys. Recent studies have shown that this condition, now known as infantile hypercalcemia type 1, is due to a genetic mutation, but about 10% of people who experience its symptoms do not have that mutation.
Not properly metabolizing vitamin D causes calcium to build up in the blood, leading to kidney stones and kidney damage, which can be fatal in babies
“This really puzzled us,” said lead researcher Dr Darrell Green, from the University of East Anglia Norwich Medical School. “So we wanted to find out exactly why this 10% seemed to have the condition, but without the gene mutation that was found to cause it.” The results of his study are published in Journal of Bone and Mineral Research.
A genetic mutation that can damage the kidneys
“In 2011, researchers discovered that some people are born with a mutation in the CYP24A1 gene, which means they can’t metabolize vitamin D properly. This causes a buildup of calcium in the blood, leading to kidney stones and kidney damage, which can be fatal in babies. It was the reason why vitamin D-enriched foods in the 1930s caused food poisoning in some people,” says Darrell Green.
“Today, some people don’t realize they have a CYP24A1 mutation until they are adults, after years of recurring kidney stones and other problems. In most cases, these patients are tested and found to have CYP24A1.” and the disorder now known as infantile hypercalcemia type 1, or HCINF1.” “However, about 10% of patients with suspected HCINF1 do not show an obvious CYP24A1 mutation and continue to have lifelong problems without proper diagnosis.”
Researchers at the University of East Anglia (UEA) collaborated with colleagues at Norfolk and Norwich University Hospital, where they worked with 47 patients, and used a combination of next-generation genetic sequencing and computational modeling to analyze blood samples from that 10%. of puzzling patients.
Dr Green explained: “My lab student, Nicole Ball, carried out a more extensive genetic analysis of six patient blood samples and we found that the physical form of the CYP24A1 gene in these apparent HCINF1 patients is abnormal.” . “This tells us that gene shape is important in gene regulation, and that this is why some people were living with HCINF1, but without a definitive diagnosis.” “On a broader scale relevant to genetics and health, we know that genes must have the correct sequence to make the correct protein, but in an added layer of complexity, we now know that genes must also have the correct physical shape.” adds the researcher.
Professor Bill Fraser of Norwich Medical School and Norfolk and Norwich University Hospital, who has co-led this research and treats HCINF1 patients in bone metabolic clinics, noted: “Genetic causes of vitamin D toxicity may left undiagnosed for long periods, well into adulthood, and sometimes come to light during pregnancy when mothers are prescribed vitamin D supplements. We also see patients with recurrent causes of kidney stones who have had this condition for many years”.
“Treatment includes avoiding vitamin D supplementation in subjects with the particular genetic abnormalities that we have identified.” “A beneficial side effect of some antifungal drugs includes altering vitamin D metabolism by reducing active vitamin D, which lowers calcium levels and may give patients a more normal quality of life, which we have begun to prescribe in some patients,” he concludes.
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