Fighting a dangerous disorder

DR KATHRYN STOWELL - Institute of Fundamental Sciences

The use of anaesthesia is regarded as one of the safest medical interventions, however, major complications—even death—can occur.

Tracing the course of a person’s reaction to anaesthesia is a complex problem, and Professor Kathryn Stowell is leading the research on a specific genetic disorder brought to New Zealand by a whaler in the 1840s.

1840 was a defining year in New Zealand’s history: colonisation was about to take off and the Treaty of Waitangi was signed between Māori and the British. At the time, the Māori population was approximately 70,000, outnumbering the 2000 or so permanent European settlers.

Adding to the count of new settlers in the 1840s was a whaler who arrived on the shores of Otaki. After farming for a time in Upper Hutt, he set down roots in Manawatū, where he married into a local Māori tribe and started a family. Eight generations later, the original family with four children grew to number 1500, some of whom carry a rare genetic disorder known as malignant hyperthermia (MH). This potentially fatal affliction is triggered by common anaesthetics administered for general anaesthesia (inhalational anaesthetics), and causes abnormal muscle contraction, resulting in rigid muscles, a high temperature, unstable heart rhythm and muscle breakdown. If untreated, it can cause death.

This one family makes the incidence of susceptible patients high in the Manawatū-Horowhenua region of New Zealand, yet their situation is rare, given that most issues with anaesthesia do not have a genetic basis.

The first evidence of malignant hyperthermia in New Zealand was in 1968, when a 20-year-old male (from this family) died during an operation on his jaw in Palmerston North Hospital.

Only a few years earlier, in 1960, the first case of MH was discovered by a Canberra-based physician, Dr Michael Denborough. He was asked to assess a boy about to have surgery who was more worried about the anaesthetic; 10 of his relatives had died under anaesthesia, and the family thought they had an ether allergy.

Developed over a period of more than 20 years, Professor Stowell’s work is known about in every MH research centre in the world, and in 2015 she was made an Officer of the New Zealand Order of Merit for her services to biomedical science.

DNA-based predictive diagnostic tests

If MH-susceptibility can be determined prior to general anaesthesia, an alternative non-triggering and safe anaesthetic procedure is used, potentially mitigating severe complications and possibly death during routine surgeries. Previously it was found using an invasive muscle biopsy that caused severe discomfort and trauma for patients, but since 1995, thanks to extensive research led by Professor Kathryn Stowell of Massey University, DNA-based predictive diagnostic tests are now also used when applicable, and her research in the field will continue, funding permitting.

Five patients have developed MH reactions in Palmerston North Hospital since 1968; two died and three survived. Each year, Professor Stowell’s team sees five to 10 new affected families, for whom the causes are becoming more complex.

The research process involves using a range of state-of-the-art molecular tools to identify causative mutations in families known to be MH-susceptible. Once mutations have been shown to segregate within a family, researchers move to functional characterisation to confirm dysregulation of calcium homoeostasis. Finally, DNA-based predictive diagnostic tests are developed and implemented.

To date, DNA-based diagnostic tests have been implemented for mutations that cause MH for over half the New Zealand families affected by the disorder. Developed over a period of more than 20 years, Professor Stowell’s work is known about in every MH research centre in the world, and in 2015 she was made an Officer of the New Zealand Order of Merit for her services to biomedical science.

She says, “It is not only important for MH, but we’re learning what makes cells tick, and what can go wrong. So our work is also applicable to a wider range of disorders.

“Our research has yielded results that affect the New Zealand population and assists medical practitioners in making clinical judgements,” she adds. This deeper understanding of MH and related disorders has contributed to a worldwide mortality rate reduction from 80% to less than 5%.

Research and awareness-building activities are ongoing, including the establishment of the Malignant Hyperthermia Association of Australia and New Zealand and the distribution of resources for the management of the disorder in an operating room environment.

Project details

Funders Palmerston North Hospital (MidCentral District Health Board)
Dates Ongoing since 1995