Issue 125 pku in the uk the early years

IMD WATCH

PKU IN THE UK: THE EARLY YEARS (1949-1979) Compiled by Suzanne Ford NSPKU Dietitian for Adults Suzanne Ford works as a Metabolic Dietitian for Adults at North Bristol NHS Trust.

She has been a Dietitian for 21 years, with six of them working in Metabolic Disease.

Memoirs of Christine Clothier, Paediatric and Metabolic Dietitian at Alder Hey Hospital (1965-1992)

HORST BICKEL ARRIVES IN BIRMINGHAM 1949

In 1949, Horst Bickel, a clever, dynamic young German doctor, joined Birmingham Children's Hospital. He was interested in phenylketonuria and proposed all 'mentally retarded' patients attending the hospital should be screened for the condition.

In March 1951, the urine of the third child who was screened, tested positive.

SHEILA JONES AND HER PIONEERING MOTHER

Sheila Jones was a 17-month-old badly brained-damaged child who could neither sit nor stand and who took no interest in her surroundings. Her Mother, refusing Figure 1: Sheila’s phenylalanine and tyrosine levels as shown in Horst Bickel’s article, The Lancet, 29 June 1953

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to accept that there was no treatment, waited every morning by the laboratory door and begged Dr Bickel to treat Sheila.

He accepted the challenge and considered how he might construct a diet based on a phenylalanine-free protein. Louis Woolf, the biochemist at Great Ormond Street, suggested removing phenylalanine from the milk protein casein, by filtering it through charcoal - after seven months covered in charcoal-smelling soot, Dr Bickel produced a phenylalanine-free casein. The prepared formula was bitter and unpalatable, but Sheila, at the age of two years and two months, accepted it. Over the next six months, Sheila's general health and appearance gradually improved as she learnt to crawl, stand and then walk.

For three years, Sheila’s dietary management continued successfully; it was compromised when her mother had a fourth child and then later, when her Mother's marriage broke up, Sheila returned to a normal diet. A video of Sheila in 1987 shows her severely brain damaged - she is sitting on the floor rocking backwards and forwards, clearly very unhappy. In February 1999, she died aged 50.

1950’S DIET FOR PKU IN BRISTOL, BELFAST AND GREAT ORMOND STREET (GOSH)

One of the first dietitians to treat phenylketonuria was Pam Williams in Bristol, and some of the difficulties of early treatment can be perceived from her records dated 1954. Casein hydrolysate was now manufactured by Allen and Hanburys, but no literature was available relating to the product. Pam had to seek advice from the dietitians in London and Belfast, who were also involved in treatment. All information was exchanged by handwritten letter and Pam had to have scoops sent from the GOSH dietitian Miss Dillistone Pam had just one small and one large scoop!

The hydrolysate, yet to be named Cymogran, was made to order only at 170 shillings per kilogram; at the time this was the average weekly wage for a working man. (It became the practice, at least until the 1970s, for the dietitian to issue all new ‘Special Products’ until they were accepted for prescription by the NHS. I was sometimes in the office issuing parcels to parents after 9pm - they didn’t seem to notice the late working hours! Such was the laborious nature of metabolic dietetics in the 1960s - and earlier.)

CHRISTINE’S EXPERIENCES IN LONDON 1964 AND LIVERPOOL FROM 1965 ONWARDS

My introduction to phenylketonuria came at five o’clock one Thursday evening in 1964 (in London), when to my horror I found on my desk a brief note saying, "Please provide a low phenylalanine diet for patient aged six weeks”. Under the guidance of Dorothy Francis at GOSH, and with the support of the hospital biochemist, I undertook the management of this child for the next 10 months. I saw the mother each Friday when the baby’s serum phenylalanine was estimated by a test which involved the use of snake venom, required complicated calculations and took over 24 hours to produce a result.

In 1964, four casein hydrolysates were available on the market, but preparing a feed was still not simple. For example, 'Albumaid XP' contained only protein and carbohydrate, so double cream was included as a source of natural fat. Each formula had to be supplemented according to its constituents; 'Ketovite liquid and tablets' contained the most complete range of vitamins, but, unfortunately, the taste caused some babies to vomit!

EXPANDING THE ‘FOODS ALLOWED FREELY’ LIST

In 1965, I went to work at Alder Hey Children's Hospital in Liverpool where less than 10 families attended the PKU clinic. We attempted to relieve a little of the stress by allowing the patients to take butter and the majority of fruit and vegetables freely. We believed the amount of fruit and vegetables consumed by a child daily to be equal to five phenylalanine portions. So, with a few exceptions, we transferred fruit and vegetables to the ‘List of Foods Allowed Freely’ and reduced each child’s allowance of phenylalanine by five.

Until then, only 33 foods were allowed freely and they were mainly condiments, flavourings and some unpronounceable ingredients used in the Baking Trade.

Examples of such gastronomic delights were: Agar Agar, Celacol powder, Edifas A, Glucono Delta Lactone and Wheatstarch. Agar Agar made very acceptable jelly, but it cost £2 per pound. Consequently, Agar Agar was only consumed by hospital inpatients! Fortunately, it was eventually replaced by a much cheaper jelly made from Carrageen Moss. Celacol powder is methyl cellulose, used to strengthen bread. Edifas A, a product which looks like stuffing out of the sofa, was used to make meringues. Glucono Delta Lactone was also used to strengthen bread. The many weeks I spent experimenting with a recipe based on this product prompted the catering officer to ask me if he should ask Liverpool Corporation to supply him with extra swill bins!

COMMUNICATION METHODS OF THE 1960s

In the 60s and 70s, many households did not have a telephone, so for these parents, communication was by handwritten letter, as the dietitian did not have a secretary. For them to contact the dietitian, they would have to use a public telephone, which could be some distance away and if there was a queue at the box, they might have to wait some time for their turn. Once through to the hospital, immediate contact was not guaranteed as the operator had to first locate the dietitian as her status did not merit a bleep. Long distance calls were expensive and limiting, as they were strictly terminated after three minutes if further money was not paid. Frequently, callers were cut off in mid-sentence having to go for more coins. www.NHDmag.com June 2017 - Issue 125

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In 1965, only two low protein products were available on prescription. Wheatstarch and 'Aminex' Rusks. Mothers had to make their own biscuits, cakes and bread.

'Aminex' Rusks.

The families who suffered most were those on The Isle of Man. Their calls were classified as long distance and, therefore, expensive; the NHS would only pay for one visit a year to the PKU clinic, one parent only to accompany the child to Liverpool. Occasionally, the dietitian was given a neighbour’s telephone number, but this method of contact entailed a long wait while the neighbour set off to fetch someone.

The delay was even longer if they were elderly, lived further away than next door, or because of the inclement weather if they had first to put on a coat. If the neighbour returned alone, no matter how willing they were, we could not rely on them to pass on a message.

PRESCRIBABLE PRODUCTS - WHAT A RANGE!

In 1965, only two low protein products were available on prescription. Wheatstarch and 'Aminex' Rusks. Mothers had to make their own biscuits, cakes and bread. It was the dietitian’s duty to demonstrate these unpredictable recipes, a task that can only be described as an ordeal! Small equipment is not available in a large kitchen and making a single loaf in a four quart bowl is not easy! Kitchen staff tended to be hostile to amateurs tinkering about in their territory and products made with Wheatstarch were most inconsistent.

At the bottom of Pam Williams’ original recipe was a footnote from Ida Stevenson, the dietitian in Belfast: "Perhaps this bread recipe will be of use to you, though as you may expect, it's not a terrific success.” She wasn’t kidding!

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Creating low phenylalanine recipes was the dietitian’s responsibility. A simple enough task, I thought: just select some suitable recipes and substitute Wheatstarch for flour. My loaves either did not rise at all or they rose through the bars of the oven! The rock-hard ginger biscuits defied both my whacks with a poker and the dog’s teeth - I had many failures! (We shouldn’t underestimate the skill and proficiency of an expert like Eileen Green. Dietitians today are indeed fortunate to have the support of her excellent recipe books and expertise.)

In 1968, low protein semolina and spaghetti were then introduced by Carlo Erba. The initial excitement at the availability of spaghetti soon diminished when it was discovered that all the instructions were in Italian and as pasta had yet to become popular in the UK, no one knew how to cook it! The introduction of tinned bread was a major step forward in dietary management as it released Mothers from the burden of having to make their own.

INTRODUCTION OF NEWBORN SCREENING AND FORMATION OF THE NSPKU

1968 also saw screening laboratories throughout the world replace the 'Phenistix' urine test with the more accurate 'Guthrie' blood test, so enabling phenylketonuric children to be identified as early as four days of age.

In 1971, a PKU baby was adopted in Liverpool by a social worker and his wife; in November 1973 they founded The National Society for Phenylketonuria and in June 1975 the

CONDITIONS & DISORDERS Not everyone, however, developed such expertise. Here are just some of the many despondent accounts that I have heard in relation to the protein hydrolysate: "I found it everywhere, down the toilet, under the carpet, in the bed."

"I held her nose until she needed air so much she had to swallow the stuff."

"In the end things got so bad, he gave up his job."

first Medical Advisory Panel met. Its members included the physician and dietitian from the clinics in Liverpool, London and Manchester.

The immediate task for the dietitians was to prepare for publication a set of diet sheets that would be accepted nationally. Though we thought it would be a fairly simple task in reality it was a nightmare.

Estimating the phenylalanine content of hundreds of foods was both time-consuming and problematic and took over a year to complete. To determine each 50 milligram portion involved numerous calculations all done by mental arithmetic with the aid of our fingers. To insure accuracy, we then checked each other's results.

The many difficult issues we addressed included converting ounces to grams and question like, ‘Should we multiply by the accurate figure 28.4 or round it up to 30?’ Portion size discussions followed and agreement was eventually reached.

UNPLEASANT AMINO ACIDS

The unpalatability of the protein hydrolysate (a perennial problem), meant that giving the protein substitute was often said to be the most exhausting, time-consuming and disturbing feature of dietary management. One baby had a fascination for clocks, so at feeding time all the portable alarm clocks in the house were assembled around him to hold his interest. If he showed a reluctance to take the feed, the Grandfather would set off the alarm bells at regular intervals, then as his mouth dropped open in surprise his mother would thrust into it a spoonful of feed.

BREAKTHROUGHS IN THE 1970S

A breakthrough came in 1970, when two amino acid mixtures, 'Aminogran' and 'PK Aid', were introduced for toddlers and older children. Although still not exactly appetising, they were well accepted and refusal, dawdling and vomiting were said to be difficulties of the past. Children of five and six years of age who required spoon feeding with the protein hydrolysate, now fed themselves, their appetites improved and they took more interest in food.

In the 1978 edition of McCance and Widdowson’s Food Tables, the amino acid tables were expanded, meaning a revision and improvement of the PKU food lists. Then, in 1979, the introduction of 'Egg Replacer’ really improved PKU living as it enabled mothers to bake an attractive variety of luxuries, such as loaves and rolls, Barm cakes, quiche, doughnuts, Parkin and meringues.

Although there have been many further, welcome improvements to the treatment of phenylketonuria, the dietary management remains stressful. Nevertheless, improvements are constantly being made and all those associated with this disorder are most grateful to Professor Horst Bickel for accepting the challenge of Sheila Jones’s Mother. www.NHDmag.com June 2017 - Issue 125

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