Rare disease: The long wait for a diagnosis

The path that lay ahead of us did not begin with a loud bang. There was no worrying ultrasound scan, no abnormal results from the newborn screening. It came quietly, gradually. During our daughter's first two months of life, we noticed that she wasn't drinking much and was barely gaining weight. By the time she was three months old, she had fallen off the percentile curve entirely and was losing weight. Although she is already our third child, we were becoming increasingly concerned.

The rarer something is, the quieter it becomes within the healthcare system. We have often sensed this silence.  

Alone in the face of uncertainty

I was already familiar with the following scenario from her siblings: I drive my child to A&E, full of worry, and five hours later I'm sent home with some Dafalgan. But this time it hit me harder. One Monday, when the scales once again showed a significantly lower weight, I grabbed my daughter and drove straight to A&E. Although her paediatrician was already monitoring the situation, I couldn't wait any longer.

I urged the doctor, saying that we «couldn't just let her wither away like a wilted flower». His response was sobering. He said she wasn't dehydrated, after all. And at just under four months old, breast milk simply wasn't enough anymore. I was given a leaflet on complementary feeding to take home and was labelled an overprotective mother.

That was the start of a long journey through the hospital's various departments. In the process, we found ourselves at the mercy of medical assessments. So I began to think about what I could do myself. First, I asked to be referred to a different doctor, as I didn't feel I was being taken seriously. This was followed by numerous phone calls and enquiries. I realised that I couldn't just leave things to the system – I had to take action.

Over the course of a year, we got to know the departments of endocrinology, gastroenterology, dietary advice, neuropaediatrics, radiology, cardiology and genetics. After this hospital marathon, we were certainly more exhausted, but not really any wiser.

Not all that rare

During our journey, I have learnt that rare diseases are not really that rare. In Switzerland, around 350,000 children and young people are affected. Yet many of these diseases have not been sufficiently researched. Worldwide, there are around 8,000 different rare diseases, but only for about 5 per cent of them are there sufficiently researched or effective treatment options. Why is this – and what does it mean for us?

There are many reasons for this: clinical trials are difficult to conduct because the sample sizes are small. Diagnoses are often made late, which means that important data is missing. The genetic complexity is high, and the analysis is time-consuming. Added to this is the fact that research is expensive and holds little commercial appeal. I have now experienced many of these issues first-hand.

The costs run to several thousand francs, and the likelihood of a definitive genetic diagnosis is around 30 per cent.

What concerns me most, however, is the lack of attention paid to this issue. Because rare diseases are not in the public spotlight, there is often a shortage of funding and scientific resources relative to the need. After all, the rarer something is, the less attention it tends to receive within the healthcare system. And it is precisely this silence that we have often felt.  

A long-awaited ray of hope

After a long wait, we were assigned a highly competent geneticist. For the first time, we felt that someone was doing everything in their power for our child. I cried during our phone call – out of relief and gratitude. At last, someone realised that with our child, we couldn't simply «wait and see». The doctor arranged for a comprehensive genetic analysis.

Shortly afterwards came the setback: the application for cost approval was rejected. The reason given was that it was not cost-effective. The idea that a child is not a cost factor seemed to have no place in this reasoning. At the same time, it was argued that the suspected diagnosis was not clearly defined at present. Given that there are 8,000 rare diseases, however, that struck me as quite logical.

Further letters from the geneticist followed, until the funding approval was finally granted. By that point, our daughter's DNA had already been stored for half a year. We would have to wait many more months for the results.  

Behind the scenes: Genetics

I thought it was a routine procedure – just another test running in the background. But it's not that simple. In fact, it all began long before that – with blood samples, forms and consent forms. And with our old familiar companion: waiting. The Trio Exome Analysis examines the child's genetic material as well as that of the parents. In the laboratory, DNA is extracted from the blood and broken down into very small pieces – like a giant jigsaw puzzle falling apart into its individual pieces.

Using modern techniques, sections of the DNA are «read» and then analysed and compared with the aid of computers. The cost runs to several thousand Swiss francs, whilst the probability of obtaining a definitive genetic diagnosis is around 30 per cent. Some genetic variations can be classified on the basis of clues or information from family history investigations. At the same time, a large proportion of genetic variants remain unclear and cannot be interpreted unambiguously – there is simply a lack of knowledge or comparable data.

If we aren't constantly busy looking for answers, we can keep our eyes open for how they develop.

It's the small steps that count

Let's get this out of the way straight away: we haven't reached the end of our long journey yet. We're still navigating between provisional diagnoses and definitive results. And that's okay. There have been moments when we've almost burst with impatience. Yet right in the thick of it, we see them: the tiniest of steps forward. They, too, come quietly and gradually. But if we're not constantly preoccupied with searching for answers, we can keep our eyes open for how things are developing. And that development happens as it happens – regardless of what the reports say.