In my line of work, about once a year, I encounter a patient with an unclassifiable disease, or Syndrome X. Generally, these are cases of congenital neurological defects, due to subtle genetic or chromosomal abnormalities, which have failed to find a place in the WHO (World Health Organisation) classification of diseases. A purist would say that it is impossible to have a single case of a syndrome, yet dictionaries allow the word to mean both a concurrent and recurrent clinical picture, so Syndrome X triumphs as a tentative diagnosis.

The prestigious scientific journal Nature has recently highlighted the true extent of the problem. A new clinical syndrome has been identified in patients with learning difficulties. The syndrome, as yet unnamed, is caused by “a very small deletion in chromosome 17”. In rather non-PC terms, in the journal’s own words, the new syndrome “is expected to explain about one per cent of undiagnosed cases of mental retardation”. Hardly the breakthrough medical geneticists were hoping for. 1 Not surprisingly, many intriguing historical diseases also qualify as Syndrome X, if not “Syndrome Unknown”. Some of these I have mentioned before [FT148:17], and I’ll take this opportunity to update developments; others have come to light since.

FT has long been interested in conditions in which people suddenly change colour. There have been cases where the victim dramatically turns orange, but the cause is now well understood: an excessive intake of carotene in vegetable and fruit juices (we are not talking about David Dickinson here). Then there are the people who – rather more slowly – turn green. This was the cause of much ribaldry in the correspondence columns after my previous article. The general tone consisted of anecdotal accounts of acquaintances who had turned green after the dye in their pyjamas ran. It’s always good to know that your public appreciates your writing.

The best-known case involves the green-skinned children of Woolpit, near Bury St Edmunds in Suffolk [FT57:39, 41; Fortean Studies vol.4, pp.81–95]. Abbot Ralph of Coggeshall, a 12th-century chronicler, recorded that a girl of about 10 and a slightly younger boy appeared from a cave (or a wolf-pit, as described below), “their skin tinged of a green colour… dressed in green clothes made of a material never seen before and speaking a language nobody could understand”. All of this is closer to legend than a possible clinical oddity. 2 Woolpit is believed to originate from ‘Wolfpittes’ where the last wolf in England is said to have died after being trapped in a pit in the 12th century. This derivation is given some authority by the Oxford Dictionary of English Place-Names which quotes the Domesday Book version (1086) Wlfpeta (‘Pit for trapping wolves’), cognate with the Old English wulf-pytt. Hence the whole account seems to be an embellishment of legends regarding feral wolf-children, most notably Romulus and Remus, the legendary founders of Rome, and the fertility cult of The Green Man, a pagan motif often carved into Christian churches of the time.

And yet, there is the one interesting detail that the children’s skin was merely “tinged of a green colour”. Could their troglodytic underground existence have led to a nutritional anæmia, the mysterious green sickness of High Victorian households, unknown today? Just possibly. I am inclined to believe that this “chlorosis” was nothing more inexplicable than normal anæmic pallor under gaslight, since it seems to have disappeared with electrification, whatever the dyed pyjama brigade might say.

In any event, a possible cause for green children has since been reported. 3 Schoolboy Rosh Kelly, then aged 11, had suffered for three years with migraines and vomiting. Doctors were baffled by the illness, which made his complexion turn green. His parents took Rosh to a nutritional laboratory, which found that he had an idiosyncratic reaction to garlic used by his father in his meals. Since the discovery, Rosh, of Heaton, Newcastle, has made a full recovery. There must be some fortean connection between a want of blood and an aversion to garlic, but it continues to elude me.

A final case revisited is altogether more serious. Remember the story of the young woman who went to sleep one night in 1920s Vienna and dreamt that she had turned into a statue? And how it seemed to come true? She had passed into catatonia, a motionless trance-like state, as a result of a truly mysterious disease later known as encephalitis lethargica (EL), or “sleepy sickness” to differentiate it from the better-known African sleeping sickness or trypanosomiasis. It was also known as von Economo’s disease after the Austrian neurologist who first described it. An American neurologist, Oliver Sacks, pioneered the treatment of EL patients decades later, using the drug L-dopa to give them a brief respite from their symptoms. His story is famously told in the Oscar-nominated 1990 film Awakenings starring Robert De Niro and Robin Williams.

The EL epidemic swept through Europe during the 1920s, killing thousands of people and leaving many more in a catatonic state. Since it followed the ‘Spanish flu’ pandemic of 1918/9, it was vicariously attributed to the same source, without a shred of evidence beyond its predilection for young adults.

Shortly after his 11th birthday in 1931, Phillip Leather fell ill. 4 He had been regarded as something of a prodigy. He was able to play four-part harmony on the piano without having been formally taught, and before starting school was able to solve jigsaw puzzles with pieces left face down. After his birthday, he began to suffer bouts of flu-like symptoms and lethargy. His eye movements became paralysed (ophthalmoplegia) and before long he was unable to walk or talk and could scarcely feed himself. In 1932, Philip was taken to see a specialist, George Auden, the father of poet WH Auden and an expert on EL. He diagnosed his patient as having contracted the disease, and Philip was admitted to the Hollymoor Mental Hospital in Birmingham, where he lived for the next 60 years. After the hospital closed in 1994, he was transferred to Yardley Green Hospital.

In 1997, the hospital put Philip’s sister Jean Price in touch with Professor John Oxford of the Royal London Hospital, who has made a study of EL and its possible connection with pandemic flu. Until that time, he had believed that all EL sufferers had already died. Jean Price gave Prof Oxford permission to take samples of brain tissue from her brother when he died, a decision hailed as “hugely significant” by Oliver Sacks in the US. The plan was to use both electron microscopy and state-of-the-art techniques such as molecular biology to pin EL on the pandemic influenza virus. At the time, he was quoted as saying: “This gives us the best chance we have had to finally pin down the cause of one of the world’s largest medical mysteries.” 5

Philip Leather died in October 2002, aged 82. If Prof Oxford ever managed to solve the mystery of EL, the world has yet to hear about it.

One of the greatest enigmas in the recent history of medicine is the precise nature of the debilitating disease that plagued the life of Florence Nightingale (1820–1910) following her return from the Crimea in August 1856. Whatever it was, although she continued to work and write at a furious pace, she spent much of the rest of her life locked away in rooms in London, often in bed, a true example of syndrome unknown.

What was generally agreed at the time was that she was suffering from “Crimea fever”, a mysterious disorder resulting in chronic malaise. Subsequent medical opinion has been divided between an organic and psychosomatic cause. Suggested organic causes have included bacterial endocarditis and brucellosis (undulant fever). Both suggestions seem vaguely absurd, since no one would have survived them for over half a century.

Psychosomatic causes include a diagnosis of bipolar disorder, ME, or the military variant of post-traumatic stress disorder (PTSD). The last diagnosis first officially emerged during the American Civil War (1861–65), as da Costa’s syndrome, rather than in the Crimean war of 1854–6.

Florence’s post-war illness is clearly depicted in a newly discovered photograph of her in 1858, two years after her return from the Crimea. In it, “her face is gaunt and her wrists are very thin”. 6

On Tuesday, 27 July 2004, there was a “mass cremation” of around 2,000 “body parts” derived from Alder Hey Hospital. The specimens were destroyed forever in a Liverpool ceremony. Almost overnight, the anatomical and pathological specimens of centuries became transmogrified into “body parts” by New Labour spin. The event was no doubt intended as a latter-day “Bonfire of the Vanities”, intended to demonise the medical profession. If so, it seriously backfired. No one wants to be a pædiatric histopathologist anymore, and anxious parents are placed on three-week waiting lists if they request an autopsy on their baby.

One of the more controversial specimens to go up in flames on that day was a fœtus labelled “Humpty-Dumpty monster” which, as I recall, came from the beginning of the second trimester of pregnancy, around 14 weeks’ gestation. (Alas, I had two cuttings from national newspapers about this specimen, mislaid them, rediscovered them and then placed them somewhere so safe I can’t recall where it is!) Nevertheless, my research notes remain, and indicate that it is only in the third trimester that anything like “Humpty-Dumpty” is recognised, notably severe cases of osteogenesis imperfecta or hydrops fœtalis. This is, apparently, the reason for the earlier specimen being retained by Alder Hey for future research purposes.

It seems reasonable to believe that the iconic Liverpool 2004 bonfire destroyed at least one specimen of a syndrome unknown.