Radboudumc researchers discover new genetic causes of magnesium deficiency Diagnosis for people with rare congenital disorder

PhD candidate Willem Bosman has shown that mutations in three different genes can cause a rare hereditary magnesium deficiency. This discovery could provide a diagnosis to people with unexplained hypomagnesemia. Bosman will defend his PhD thesis on September 29.

Magnesium is an essential mineral in our body. It strengthens bones, enables muscle contraction, and is involved in energy-producing processes. A severe deficiency can lead to symptoms such as muscle cramps, fatigue, and epilepsy. Congenital magnesium deficiency is rare, affecting about one in forty thousand people.

During his PhD research at Radboudumc, under the supervision of professor Joost Hoenderop and magnesium researcher Jeroen de Baaij, Willem Bosman searched for genetic mutations that could cause such a severe deficiency. He studied several patients and demonstrated in his dissertation that mutations in three different genes can explain the deficiency.

Channels

For these three causes, Bosman focused on the kidneys, which play a crucial role in the body’s magnesium balance. The kidneys produce pre-urine, which later exits the body as urine via the bladder. From this pre-urine, the kidneys can reabsorb valuable substances, including magnesium. The cells lining the pre-urine have special channels—tiny tunnels through which magnesium can pass. Bosman showed that mutations in the genes coding for these channels (TRPM6 and TRPM7) can completely halt magnesium absorption. As a result, magnesium is lost through the urine.

The kidney cells form the barrier between the pre-urine and the blood vessels. Mutations in the gene involved in the transport process of magnesium into the blood (CNNM2) form the second identified cause of magnesium deficiency. Bosman explains: ‘Sometimes such a mutation only leads to magnesium deficiency, but it can also cause developmental delays. We wanted to better understand this condition and assess its severity. Based on the specific mutation, we can now better predict whether the disease will be mild or more severe.’

Connect people

Thirdly, Bosman investigated mutations in the TARS2 gene, which plays a role in the cell’s energy metabolism. It was already known that such mutations could cause disease, affecting muscle and brain development. However, it had not previously been linked to magnesium. ‘I showed in four patients that they all suffer from magnesium deficiency, meaning it is part of the disease profile’, says Bosman. ‘Doctors can now take this into account in their treatment plans.’

These newly discovered causes can provide a diagnosis for people worldwide with unexplained magnesium deficiency. ‘In my experience, these people are very relieved when they finally know what’s wrong’, says De Baaij. ‘We can also give them better advice about their hereditary condition, for example, if they want to have children. Additionally, it’s very valuable to connect people with such a rare condition to others who are affected—especially parents of children with the disorder.’

More information about the thesis defense

PhD defense on September 29, 2025, at 12:30 PM by Willem Bosman. Title of dissertation: Many Meetings: Traditional and Novel Players in Magnesium Reabsorption (available online after September 29). Supervisors: Prof. Dr. Joost Hoenderop and Prof. Dr. Jeroen de Baaij. The defense can be followed via this livestream. Expertise on rare congenital magnesium deficiency is centralized in the European network ERKNet.

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