Alan Moncrieff

Treatment of Phenylketonuria with a Diet Low in Phenylalanine

Phenylketonuria is one of the very few conditions in which mental deficiency is associated with a demonstrable metabolic error. It has been suggested that the mental defect is due to an intoxication by phenylalanine or one of its motabolites, and that the mental deficiency may be relieved by feeding a diet low in phenylalanine (Woolf and Vulliamy, 1951). Such a diet must be adequate to permit normal health and growth. All dietary proteins are about equally rich in phenylalanine (Block and Bolling, 1951), and a suitable diet can therefore be devised only by supplying the bulk of the nitrogen as a mixture of amino-acids. While it would be possible to mix pure amino-acids to obtain such a diet, the cost would render any long-term treatment of even a few cases impossible. Protein hydrolysates have been commercially available for some years, and it is known that they can be freed from phenylalanine, tyrosine, and tryptophan by passing through a column of charcoal (Schramm and Primosigh, 1943). It seemed likely that a suitable amino-acid mixture could be obtained at a reasonable cost by passing an acid hydrolysate of casein through charcoal and adding tyrosine and tryptophan. This was suggested by one of us (L. I. W.) to Dr. H. Bickel, who at that time had a suitable phenylketonuric patient under his care. Bickel carried out the preparation of the suggested diet, fed his patient on it, and reported a very marked improvement in the childs mental condition (Bickel, Gerrard, and Hickmans, 1953). No psychometric measurements were made, and it seemed worth while repeating this work, making as objective and as accurate measurements as possible of intelligence level before feeding the diet and at intervals after. Electroencephalograms were used as a second objective measurement. The findings are described for two children, both aged 2 years 8 months at the start, who have been fed g diet low in phenylalanine for nine and ten months respectively; marked intellectual improvement resulted, and the E.E.G. became normal in the one case in which it was previously abnormal. A third child, aged 5 years 5 months, has been fed this diet for a shorter period, but presents interesting features, and the preliminary finding of intellectual improvement is described.

The Dietary Treatment of Phenylketonuria

Phenylketonuria is an inborn error of the metabolism of phenylalanine associated almost invariably with grave mental deficiency, and often with epilepsy resembling petit mal. It was suggested that the mental deficiency was due to an intoxication by phenylalanine or one of its metabolites and might be relieved by feeding a diet low in phenylalanine (Woolf and Vulliamy, 1951). An economically practicable form of such a diet, based on a charcoaltreated casein acid hydrolysate, was devised by one of us (L.I.W.) and first fed to a phenylketonuric child by Bickel, Gerrard and Hickmans (1953).* They reported a dramatic improvement in mentality in their patient and Woolf, Griffiths and Moncrieff (1955), using objective psychometric methods, found a marked improvement in three other cases. Since then there have been a number of reports of the successful application of the dietary treatment of phenylketonuria (e.g., Armstrong and Tyler, 1955; Braude, 1956; Homer and Streamer, 1956; Blainey and Gulliford, 1956), and it is evidently being widely adopted. We are reporting here our experiences both with the original three patients (now followed for a further 32 months) and with a further seven phenylketonuric children who have been treated on the diet for periods varying from 11 to 34 months. One of these has been treated from the age of a few weeks for over two years, and has remained in the normal range of intelligence. Another, treated from the age of 4 months, has not shown the further deterioration in intelligence which would be expected if untreated. The rest have all improved in intelligence rating; in two of the four cases with fits these ceased soon after the children were placed on the diet, and the E.E.G. became nearly normal (cf. Wolf, 1956). Of the children who have been or are being treated with the diet at this hospital, all but eight are reported here. Of these eight, one lives at a considerable distance, while the other seven have been

Sucrosuria with Mental Defect and Hiatus Hernia

Three instances are described of the association in early childhood of sucrosuria, mental retardation and an anomaly of the lower end of the ocsophagus, thus producing the three types of congenital abnormality in the one subject—inborn metabolic error, mental defect and an anatomical abnormality. Autopsy findings in one case revealed a congenital defect in the brain, thus ruling out any hypothesis that the mental retardation might be associated with a sucrosaemia. It is concluded that the sucrosuria resulted essentially from rapid absorption of the unsplit disaccharide but technical difficulties made it impossible to investigate further the failure of splitting or its degree. The previous, scanty, literature mostly deals with similar instances, as far as the sucrosuria is concerned, of exogenous origin. Careful study of the sugars fed and subsequently passed in the urine revealed a more complicated story than that of excessive alimentary absorption of sucrose and urinary excretion. Provisional “normal” values for urinary sugars obtained by chromatography are suggested. The close association of lactose and sucrose in the diet in relation to the occurrence of sucrose in the urine seems definitely established in the cases reported. Glucose metabolism was unaffected

Infection in the newborn baby.

It is a great honour to give the Charles West Lecture, and I appreciate it all the more because this is the centenary year of the famous hospital he founded in Great Ormond Street. I am also happy that on the first occasion this lecture is given by a London paediatrician it has fallen to the lot of one who also had the privilege of serving the Middlesex Hospital, where West was a lecturer on midwifery in the years before he devoted his undivided attention to the sick child. I have chosen the subject of infection in the newborn baby partly because of Wests own interest in this subject as an obstetrician and also because I believe it was through this subject, encountered when he was studying in Dublin, that he first became interested in the sick child.

Further Experiences in the Treatment of Phenylketonuria

Since the last paper from the group at the Hospital for Sick Children, Great Ormond Street, was published (Woolf et al., 1958), further experience has been gained. The patient on whom they reported (their Case 1), and who has an unaffected twin, continues to make good progress and has gone to an ordinary primary school with the twin sister. (The affected twin, born in February, 1955, gave a positive test for phenylpyruvic acid in the urine on the seventeenth day of life, and the special diet was started shortly after her admission to hospital at the age of 3 weeks.) Her I.Q. remains in the mid-eighties, whereas her sister scores over 100. Seen together there seems little to choose between them, except the interesting point that the afyected child is in fact a little taller and heavier than her normal sister, and her hair is darker. She takes her special food to school. This has been made possible through the closest co-operation by the education authority. She is also lucky in having an intelligent mother.

Dietetic treatment of phenylketonuria: a follow-up study.

Ordinary school indicates placement with the normal educational system. E.S.N. indicates placement in a school for the educationally subnormal. T.C. indicates placement at a training centre. Hospital indicates placement in a hospital for the subnormal. Rudolph Steiner indicates placement in a special unit. * Consultant Chemical Pathologist, the Hospital for Sick Children, Great Ormond Street, London W.C.I,

The Infantile Type of Gaucher's Disease.

The curious and rare form of splenomegaly which Gaucher first described in 1882 is commonly believed to originate in early childhood, but the majority of the forty to fifty reported cases have sought relief from symptoms arising in adult life. The modern view that the disorder is an inborn error of tissue metabolism would suggest that examples might occur and be discovered accidently in infancy. The object of this paper is to describe a case of Gauchers splenomagaly where death took place at the age of four months. Curious symptoms pointing to some gross disorder of the nervous system were also present, and this appears to be so constant a feature of the few cases of Gauchers disease in infancy already recorded as to constitute a distinct clinical picture, differing from Gauchers disease in adults and presenting many points of interest in diagnosis and pathology. Papers by Oberling and Woringerl in France, and by Dienst2 in Germany, contain accounts of the dozen or:so cases already recorded, together with a full discussion of the condition and of the literature on this subject.

Child Health and the Future

Contains a discussion of infant and child mental health, unintentional injury issues, safety, interpersonal violence, and self-harm.

Lead Absorption in Children

between the teeth on either side of the jaw, a characteristic cracking sensation is detected in the region of the medial pterygoid muscle as the impediment to movement is overcome. Following this action normal mouth opening is restored. The patient does not experience any postoperative pain and there is no tendency to recurrence. Care must of course be taken not to exert excessive force when opening the mouth in this manner, and a wide-bladed instrument, such as a Featherstone gag, should be used in order to avoid damage to the crowns of teeth or the accidental displacement of an upper second premolar into the maxillary sinus. The cases examined appear to have had no common aetiological factor in so far as the injection technique and the nature of the analgesic solution is concerned. The most likely cause appears to be that with the modern, thin, sharp hypodermic needle there is a greater risk of penetrating a small artery. Rupture of the vessel would then cause haematoma formation with subsequent organization of a band of fibrous tissue in the vicinity of the medial pterygoid muscle. This would explain the gradual onset of the trismus and the mechanical locking effect achieved, and also account for the recent increase in the condition.-We are, etc.,

Current Problems in the Tuberculosis of Childhood Infection, Diathesis, Artificial Pneumothorax, Preventive Inoculation

It is a striking fact that tuberculous infection in infancy and childhood has not diminished in proportion to that of the adult. Aschoff,(4) quoting Gxottstein, has particularly emphasised this, and he points out that there are still many problems with regard to the pathogenesis of phthisis yet to be solved. A review of certain views on these problems in the light of recent contributions to their study has been undertaken here almost entirely with regard to lung infections.