It became a medical mystery that left parents and families heartbroken following a wave of unexplained baby deaths.
Now, researchers from the University of East Anglia (UEA) have finally solved the 80-year puzzle dating as far back to the 1930s and 1940s.
It comes following the introduction of vitamin D to fortify foods such as milk, bread, cereal, and margarine in a bid to eradicate rickets in children.
But the discovery of a condition called infantile hypercalcaemia type 1 (HCINF1), which is caused by a gene mutation, had revealed that those affected could not metabolise the vitamin.
In turn it would cause a build-up of calcium in the blood and lead to kidney damage and kidney stones.
And it is still affecting patients today.
Curiously, 10pc of patients experiencing symptoms did not have the genetic mutation HCINF1.
Shelley O’Connor, 34, from Norwich, was diagnosed with HCINF1 eleven years ago when she fell pregnant with her first child, Fred, at the age of 23.
She had started to take pregnancy supplements, which included vitamin D, but she began to experience a pain so severe that midwives thought she was going into early labour at just 23 weeks.
She said: “It was very frightening. I was in a lot of pain, and the midwives thought I was going into labour.
“I was really scared for the baby, but when I had an MRI, they found out that it was actually a kidney stone caused by taking vitamin D as a pregnancy supplement.”
Thankfully, her son was born safe and well at full term, and Ms O’Connor has since gone on to have another two children.
“I was diagnosed with HCINF1 and it did explain a lot because I had experienced things like abdominal pain and UTIs in childhood,” she added.
“I was really pleased to be invited to take part in the research, and I hope the findings go on to help others like me.”
Her condition has taken its toll as she now regularly passes kidney stones and needs to take pain medication. She also has an operation every six months to clear the calcium build-ups that lead to kidney stones.
The UEA team collaborated with colleagues at the Norfolk and Norwich University Hospital (NNUH), where they worked with 47 patients.
They used a combination of next generation genetic sequencing and computational modelling to study blood samples from those 10pc of patients.
Lead researcher, Darrell Green, from the UEA’s Norwich Medical School explained what went on behind the scene.
Dr Green said: "A PhD student in my laboratory, Nicole Ball, carried out a more extensive genetic analysis of six patient blood samples.
"This tells us that gene shape is important in gene regulation - and that this is the reason why some people lived with HCINF1 but without a definitive diagnosis.
“On a wider scale relevant to genetics and health, we know that genes must have the correct sequence to produce the correct protein, but in an added layer of complexity, we now know that genes also have to have a correct physical shape.”
Genetic causes of vitamin D toxicity can be left undiagnosed for long periods, including well into adulthood. The researchers now plan to investigate the role of gene shapes in other disorders such as cancer.
This research was led by UEA in collaboration with the John Innes Centre, Nnuh, Croydon University Hospital, and the Royal Hospital for Children in Glasgow.
Where it started
The puzzle began in the early 1900s, when more than 80pc of children in industrialised Europe and North America were affected by rickets, which causes bone pain, poor growth and soft, weak, deformed bones.
The discovery that sunlight prevented rickets led to fortification of foods with vitamin D, which all but eradicated the disease by the 1930s.
But outbreaks of vitamin D intoxication in infants led to fortification bans in many European countries by the 1950s.
Foods such as dairy products had been fortified with vitamin D, but it led to a number of baby deaths, and was eventually banned in many countries except for in breakfast cereals and margarine.
In 2011, researchers found that some people are born with a mutation in the CYP24A1 gene, which means they cannot metabolise vitamin D properly.
This causes a build-up of calcium in the blood, leading to kidney stones and kidney damage, which can be fatal in babies.
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