Hypomagnesemia with secondary hypocalcemia (HSH)

Hypomagnesemia with secondary hypocalcemia (HSH) is a rare disorder caused by a defect (mutation) in the genetic material (DNA). It concerns a mutation in the magnesium TRPM6 channel, which plays an important role in the (re-) uptake of magnesium in the gut wall and the renal tubules.

By a mutation in the gene TRPM6, the intestines cannot absorb sufficient magnesium. In addition, the kidneys are also not able to re-uptake magnesium maximally due to which it is excreted into the urine. This can result in low magnesium levels in the blood shortly after birth, often leading to seizures and muscle spasms. If left untreated, this can lead to (severe) developmental disturbances or even death. Due to the low magnesium levels in the blood, other mineral disorders such as a low level of calcium and a suppression of the production of the parathyroid hormone can occur.

HSH based on TRPM6 mutations is a hereditary disease, which is inherited autosomal recessive. This means that a person will have this condition if he or she has a mutation in both TRPM6 genes (ie in both the genetic material derived from father as that of mother). Because two mutations are required, and the mutations are relatively rare, the likelihood that children of a patient with the disease have HSH is also not large. Siblings of patients on the other hand do have a high probability (25%) in order to have HSH. Family members with only one mutation seem to have no clinical symptoms.

The diagnosis HSH is made on the basis of a genetic test in which a mutation is detected in both TRPM6 genes.

There is no causal treatment available to treat the underlying disorder. In other words, the underlying problem (the dysfunctional TRPM6) cannot be remedied. The treatment, therefore, consists of the treatment of the mineral salt and disorders, and is directed to the prevention or treatment of complaints. This often includes (lifetime) treatment with magnesium tablets in high doses.

If left untreated, the prognosis is poor and will lead to severe developmental disabilities and death. With treatment, HSH in the majority of cases leads to chronic deterioration of renal function for which ultimately renal replacement therapy (dialysis, renal transplantation) is necessary.