328
SCREENING FOR PHENYLKETONURIA SIR,-You describe (Jan. 18, p. 178) the very efficient
phenylketonuria register in Liverpool and you rightly emphasise the need for better centralisation of the screening programme in the United Kingdom, suggesting that one laboratory might serve the whole country. You further ask the question whether " screening is any less successful in Scotland with just one laboratory than in England with 34 ". I am not in a position to answer this question, but I would point out that screening is more than a laboratory procedure, it is a human exercise which demands good communication between the patient, the local health authority, the screening laboratory, and the unit that gives the full sophisticated and experienced clinical and biochemical back up for the confirmation of diagnosis and the supervision of treatment.1 This would be difficult to obtain in any unit which screens more than 75,000 babies a year, since this demands a close relationship with many local authorities-26 in our particular case-as well as accepting 10-12 new metabolic problems each year in addition to clarifying the position in many indeterminate cases in the screening programme. I have long felt that the United Kingdom could be served by 10 efficiently organised regional biochemical genetics laboratories which would have further responsibilities in addition to screening and which would be closely linked with a regional cytogenetics unit, and I would be very distressed if serious consideration were given to the creation of a single screening unit. Willink Biochemical Genetics
Laboratory, Royal Manchester Children’s Hospital, Pendlebury, near
Manchester M27 1HA.
G. M. KOMROWER.
" work of all aides " doing such testing needs to be under the constant supervision of experienced medical doctors. Does universal periodic developmental assessment find the handicaps earlier ? Not many years ago, even in a university city with a medical school, children with cerebral palsy arrived for treatment at an average age of 2t years. Recently, in an area where periodic developmental assessment by doctors of child health clinics has been done for several years, a survey showed that 90% of cerebral-palsied children had started treatment during their first year, the remaining 10% being children recently coming into the
area.
Does earlier recognition of visual handicap, hearing deficity, cerebral palsy, mental or social handicap, improve the ultimate outcome ? It is not easy to find unequivocal evidence that it does in all these cases, but it seems possible and likely that it will be found to be true. It seems better 6 months rather than 18 months of age, and the National Child Development Survey has shown that children who still had squints uncorrected when they
to treat a cataract at
got to school were at a disadvantage. There is also need for research on methods and efficiency of periodic developmental assessment. There is certainly a great desire among doctors, notably those formerly in local authority services for children, to do these assessments; they would gladly cooperate in such research. There is need too for research on whether earlier treatment gives better results. There is at present some research in progress on results of Bobath treatment of cerebral-palsied children started under the age of 1 year. Perhaps the D.H.S.S. will see these areas as areas in which it will, under the Rothschild scheme, actively promote research. 35 Bloomfield Terrace, London SW1.
RONALD MAC KEITH.
UNIVERSAL PERIODIC DEVELOPMENTAL ASSESSMENT
SIR,-Professor Holland (Dec. 21, p. 1494) discusses screening in infancy and childhood. He starts from the " at risk " concept and rightly refers to the dangers of a " risk register " based on unvalidated characteristics and assumptions of outcome. But he does not present clearly the case for universal periodic developmental assessment of children.
Developmental assessment differs from looking for specific disorders, such as dislocation of the hip, heartdisease, or hernias. In problems of developmental delay, the mother suspects, or the doctor finds, developmental delay in one or more of the four main fields of development - movement, vision, hearing and language, everyday and social skills. The child is then referred to a centre for assessment and care for confirmation of the delay, identification of the underlying disorder, and diagnosis of the cause of The assessment must be comprehensive because that. delay in a particular field can have various causes. Delay in walking can be due to visual, motor, learning, or social handicap or to combinations of these. The second reason for comprehensive assessment is that handicap is usually multiple. A person who is mentally handicapped can also have a major refractive error, recognition and treatment of which is likely to help him or her. Developmental assessment is not a method of yes-no screening; the doctor doing it observes the quality of the child’s approach and of his achievement. Parts can be carried out by aides-e.g., vision testing of children over the age of six-and for pre-school children who are not brought to see the doctor for periodic medical examination and developmental assessment, the health visitor can do some tests when she visits the home. But her work and the 1.
Komrower, G. M. Pediatrics, Springfield, 1974, 53, 182.
A VARIANT OF PHENYLKETONURIA
SiR,-We were interested by the letter from Dr Bartholome (Dec. 28, p. 1580) reporting a patient with phenylketonuria and normal phenylalanine-hydroxylase activity. We reported a similar case1 in which the activity of phenylalanine p-hydroxylase was normal. This was measured by a method described previously,2 on a specimen obtained by needle liver biopsy. In the same paper we also described a pair of siblings with an identical syndrome (progressive neurological disease, chemical phenylketonuria, and failure to respond to a low-phenylalanine diet, in spite of satisfactory control of phenylalanine levels), in whom enzyme activity was not measured. All 3 patients have since died of bronchopneumonia at the ages of 2, 6, and 7 years. The clinical picture presented by these 3 cases was quite unlike that seen in any of the other 250 patients with classical or atypical phenylketonuria seen at the Hospital for Sick Children, London, since 1949. It is likely that Dr Bartholome’s and our cases represent a previously undescribed variant of the disease, though it is possible that the case described by Crome3 falls into the same category. A more detailed report of our 3 cases is in preparation. We have postulated that the disorder is due to a defect in the metabolism of biopterin, the natural cofactor for phenylalanine hydroxylase. An abnormality of the enzyme dihydropteridine reductase,4 which plays a vital role in the cofactor system, is a likely possibility. In neural tissue this enzyme and biopterin are involved in the hydroxylation of tyrosine to dihydroxyphenylalanine (dopa) and of trypto1. 2.
Smith, I. Archs Dis. Childh. 1974, 49, 245. McClean, A., Marwick, M. J., Clayton, B. E. J. clin. Path. 1973, 26,
3. 4.
Crome,
678. L. J. Neurol. 1962, 25, 149. Kauffman, S. Advanc. Enzymol. 1971, 35, 245.
SCREENING FOR PHENYLKETONURIA SIR,-You describe (Jan. 18, p. 178) the very efficient
phenylketonuria register in Liverpool and you rightly emphasise the need for better centralisation of the screening programme in the United Kingdom, suggesting that one laboratory might serve the whole country. You further ask the question whether " screening is any less successful in Scotland with just one laboratory than in England with 34 ". I am not in a position to answer this question, but I would point out that screening is more than a laboratory procedure, it is a human exercise which demands good communication between the patient, the local health authority, the screening laboratory, and the unit that gives the full sophisticated and experienced clinical and biochemical back up for the confirmation of diagnosis and the supervision of treatment.1 This would be difficult to obtain in any unit which screens more than 75,000 babies a year, since this demands a close relationship with many local authorities-26 in our particular case-as well as accepting 10-12 new metabolic problems each year in addition to clarifying the position in many indeterminate cases in the screening programme. I have long felt that the United Kingdom could be served by 10 efficiently organised regional biochemical genetics laboratories which would have further responsibilities in addition to screening and which would be closely linked with a regional cytogenetics unit, and I would be very distressed if serious consideration were given to the creation of a single screening unit. Willink Biochemical Genetics
Laboratory, Royal Manchester Children’s Hospital, Pendlebury, near
Manchester M27 1HA.
G. M. KOMROWER.
" work of all aides " doing such testing needs to be under the constant supervision of experienced medical doctors. Does universal periodic developmental assessment find the handicaps earlier ? Not many years ago, even in a university city with a medical school, children with cerebral palsy arrived for treatment at an average age of 2t years. Recently, in an area where periodic developmental assessment by doctors of child health clinics has been done for several years, a survey showed that 90% of cerebral-palsied children had started treatment during their first year, the remaining 10% being children recently coming into the
area.
Does earlier recognition of visual handicap, hearing deficity, cerebral palsy, mental or social handicap, improve the ultimate outcome ? It is not easy to find unequivocal evidence that it does in all these cases, but it seems possible and likely that it will be found to be true. It seems better 6 months rather than 18 months of age, and the National Child Development Survey has shown that children who still had squints uncorrected when they
to treat a cataract at
got to school were at a disadvantage. There is also need for research on methods and efficiency of periodic developmental assessment. There is certainly a great desire among doctors, notably those formerly in local authority services for children, to do these assessments; they would gladly cooperate in such research. There is need too for research on whether earlier treatment gives better results. There is at present some research in progress on results of Bobath treatment of cerebral-palsied children started under the age of 1 year. Perhaps the D.H.S.S. will see these areas as areas in which it will, under the Rothschild scheme, actively promote research. 35 Bloomfield Terrace, London SW1.
RONALD MAC KEITH.
UNIVERSAL PERIODIC DEVELOPMENTAL ASSESSMENT
SIR,-Professor Holland (Dec. 21, p. 1494) discusses screening in infancy and childhood. He starts from the " at risk " concept and rightly refers to the dangers of a " risk register " based on unvalidated characteristics and assumptions of outcome. But he does not present clearly the case for universal periodic developmental assessment of children.
Developmental assessment differs from looking for specific disorders, such as dislocation of the hip, heartdisease, or hernias. In problems of developmental delay, the mother suspects, or the doctor finds, developmental delay in one or more of the four main fields of development - movement, vision, hearing and language, everyday and social skills. The child is then referred to a centre for assessment and care for confirmation of the delay, identification of the underlying disorder, and diagnosis of the cause of The assessment must be comprehensive because that. delay in a particular field can have various causes. Delay in walking can be due to visual, motor, learning, or social handicap or to combinations of these. The second reason for comprehensive assessment is that handicap is usually multiple. A person who is mentally handicapped can also have a major refractive error, recognition and treatment of which is likely to help him or her. Developmental assessment is not a method of yes-no screening; the doctor doing it observes the quality of the child’s approach and of his achievement. Parts can be carried out by aides-e.g., vision testing of children over the age of six-and for pre-school children who are not brought to see the doctor for periodic medical examination and developmental assessment, the health visitor can do some tests when she visits the home. But her work and the 1.
Komrower, G. M. Pediatrics, Springfield, 1974, 53, 182.
A VARIANT OF PHENYLKETONURIA
SiR,-We were interested by the letter from Dr Bartholome (Dec. 28, p. 1580) reporting a patient with phenylketonuria and normal phenylalanine-hydroxylase activity. We reported a similar case1 in which the activity of phenylalanine p-hydroxylase was normal. This was measured by a method described previously,2 on a specimen obtained by needle liver biopsy. In the same paper we also described a pair of siblings with an identical syndrome (progressive neurological disease, chemical phenylketonuria, and failure to respond to a low-phenylalanine diet, in spite of satisfactory control of phenylalanine levels), in whom enzyme activity was not measured. All 3 patients have since died of bronchopneumonia at the ages of 2, 6, and 7 years. The clinical picture presented by these 3 cases was quite unlike that seen in any of the other 250 patients with classical or atypical phenylketonuria seen at the Hospital for Sick Children, London, since 1949. It is likely that Dr Bartholome’s and our cases represent a previously undescribed variant of the disease, though it is possible that the case described by Crome3 falls into the same category. A more detailed report of our 3 cases is in preparation. We have postulated that the disorder is due to a defect in the metabolism of biopterin, the natural cofactor for phenylalanine hydroxylase. An abnormality of the enzyme dihydropteridine reductase,4 which plays a vital role in the cofactor system, is a likely possibility. In neural tissue this enzyme and biopterin are involved in the hydroxylation of tyrosine to dihydroxyphenylalanine (dopa) and of trypto1. 2.
Smith, I. Archs Dis. Childh. 1974, 49, 245. McClean, A., Marwick, M. J., Clayton, B. E. J. clin. Path. 1973, 26,
3. 4.
Crome,
678. L. J. Neurol. 1962, 25, 149. Kauffman, S. Advanc. Enzymol. 1971, 35, 245.
