- people are clearly not well;
- their adverse symptoms make a distinct syndrome which can be recognised in other patients
- some of those other patients are relatives of the first case. The disease runs in families, to the extent that, in some cases, you could find distant cousins by their shared medical peculiarities.
Being of historical interest and colorful is not sufficient to trigger a Blob on alkaptonuria but a four page article in last week's Nature adds sufficient weight. A father’s fight to help his sons - and fix clinical trials - Nick Sireau’s quest to give his sons weedkiller could help thousands struggling with rare genetic conditions. That about sums up the sensational aspects of the essay. The problem is that nobody should want to 'fix clinical trials' unless it is the share-holders and sales-force of the pharmaceutical company which is marketing the therapy. Mr Sireau's boys were born with alkaptonuria and he was determined to find a cure, preferably before the lads grew up and started to show the worst of the symptoms - typically in their 30s.
Nitinisone costs about $50,000 or $60,000 per person per year and they've done the figures on using it to treat Type I Tyrosinaemia a disease caused by a defect in the same pathway as alkaptonuria and PKU. Mr Sireau believes that it will have positive effects for his chaps but there is no good evidence that it makes the adverse symptoms measurably better. The US Food and Drug Administration FDA won't allow the drug to be marketed without that sort of positive benefit data. Nobody should be allowed to pay so much for something that doesn't work. Especially, this should be stopped if somebody else is picking up the bill. It seems that Sireau's advocacy group has blagged the European authorities to accept a less standard of 'success'. If, under treatment, the concentration of homogentisic acid falls significantly then that will be enough - it will be what is called a surrogate marker. We-the-tax-payer will then start paying for the drug regardless of whether the 'real' adverse symptoms like pain, joint flexibility, heart dysfunction, eye disease improve. If it don't work; don't pay for it. It's better to grimace and bear it without treatment than to grimace just as much and be out of pocket. I dunno, I'm not certain about the ethics or economics here: you read the Nature piece and decide where you want your share $50,000 allocated. Trolleys? More nurses? Pay-hike for nurses? Mental health? New children's hospital? OR "I'll keep my share of tax-dollars, thanks very much, less tax will mean I can build my much desired (and to be admired) gazebo in the back garden"
A final grimace and bear it irony. Archibald Garrod had three sons. They all joined the army in WWI and they were all killed: Thomas 10th May 1915; Alfred 20th Jan 1916; Basil 4th Feb 1919 (Spanish 'flu). No amount of money could save them.