Summary of Researchers Solve 80-Year-Old Vitamin D Medical Mystery That Claimed Infant Lives:
It discusses the discovery of a long-standing medical mystery that causes kidney damage in children and can be fatal in babies. Infantile hypercalcemia type 1 is caused by a gene mutation which leads to an accumulation of calcium in the blood, resulting in kidney stones and kidney damage. In some cases, 10 percent of patients experiencing symptoms did not have the gene mutation. UEA researchers used next-generation genetic sequencing and computational modeling to study blood samples from these patients and found that the physical shape of the CYP24A1 gene was abnormal. This study has implications for other genetic disorders such as cancer.
Infantile hypercalcemia type 1 is a rare genetic disorder that affects the regulation of calcium levels in the body, leading to an accumulation of calcium in the blood and resulting in kidney stones, kidney damage, and other symptoms. Scientists at the University of East Anglia have discovered that the physical shape of the CYP24A1 gene is abnormal in some cases where individuals have the symptoms of infantile hypercalcemia type 1 but do not have the gene mutation. This research has implications for other genetic disorders such as cancer.
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Infantile Hypercalcemia Type 1
Infantile hypercalcemia type 1 is a rare genetic disorder that affects the regulation of calcium levels in the body. Individuals with infantile hypercalcemia type 1 typically present with elevated levels of calcium in the blood, which can result in a range of symptoms including vomiting, constipation, dehydration, irritability, and developmental delays. In severe cases, infantile hypercalcemia type 1 can lead to life-threatening complications such as kidney failure and cardiac arrhythmias.
The Medical Mystery
Scientists at the University of East Anglia have solved a long-standing medical mystery that causes kidney damage in children and can be fatal in babies. Those with the condition are unable to metabolize vitamin D properly. This leads to an accumulation of calcium in the blood and causes kidney stones and kidney damage, which can be fatal in babies.
The 1930s and 1940s
This resulted in a surge of infant fatalities during the 1930s and 1940s, as a result of fortifying foods such as milk, bread, cereal, and margarine with Vitamin D in an effort to eliminate rickets in children.
The Gene Mutation
Recent research had shown that the condition, now known as infantile hypercalcemia type 1, is caused by a gene mutation. But curiously, around 10 percent of patients experiencing symptoms do not have the genetic mutation.
The Research
The UEA team collaborated with colleagues at the Norfolk and Norwich University Hospital, where they worked with 47 patients.They used a combination of next-generation genetic sequencing and computational modeling to study blood samples from those ’10 percent’ of puzzling patients.
Dr. Green said: “A Ph.D. student in my laboratory, Nicole Ball, carried out a more extensive genetic analysis of six patient blood samples and we found that the physical shape 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 the reason why some people lived with HCINF1 but without a definitive diagnosis,” he added.
The Treatment
Prof Bill Fraser, from both Norwich Medical School and the Norfolk and Norwich University Hospital, co-led the study and treats HCINF1 patients in metabolic bone clinics.He said: “Genetic causes of vitamin D toxicity can be left undiagnosed for long periods, well into adulthood, sometimes coming to light during pregnancy when fortification of mothers with vitamin D happens. We also see patients with undiagnosed causes of recurrent renal stones who have had this condition for many years. Treatment includes avoidance of vitamin D supplementation in subjects with the particular genetic abnormalities we have identified.”
“A beneficial side effect to some anti-fungal medications includes alteration of vitamin D metabolism lowering active vitamin D, which decreases calcium levels and can give patients a more normal quality of life, which we have started to prescribe in some patients,” he added.
The Future
The researchers now plan to investigate the role of gene shapes in other disorders such as cancer.
Case Study – Shelley O’Connor
Shelley O’Connor, 34, from Norwich, was diagnosed with infantile hypercalcemia type 1 eleven years ago when she fell pregnant with her first child 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 an early labor at just 23 weeks.
“It was very frightening,” she said. “I was in a lot of pain, and the midwives thought I was going into labor. 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 Shelley 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 said.
But the condition has taken its toll. Shelley now regularly passes kidney stones and needs to take pain medication. She also has to have an operation every six months to clear the calcium build-ups that lead to kidney stones.
“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,” she said.
