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Hartnup Disease in Psychiatric Practice: Clinical and Biochemical Features of Three Cases by L

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Hartnup Disease in Psychiatric Practice: Clinical and Biochemical Features of Three Cases by L J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.23.1.40 on 1 February 1960. Downloaded from J. Neurol. Neurosurg. Psychiat., 1960, 23, 40. HARTNUP DISEASE IN PSYCHIATRIC PRACTICE: CLINICAL AND BIOCHEMICAL FEATURES OF THREE CASES BY L. A. HERSOV* and R. RODNIGHT From the Maudsley Hospital, London In a previous paper the case history was given of abnormality and examination of her family revealed a 10-year-old boy admitted to hospital for a an affected sister. The present paper describes the psychotic illness associated with a photosensitive follow-up of our original case for six years, together skin rash (Hersov, 1955). The condition resembled with as much information on his family as it has classical pellagra, and although no dietary reason been possible to obtain, and the clinical and bio- for a vitamin deficiency was apparent, a good chemical features of the second family. A pre- response was obtained to treatment with nicotin- liminary report of some of the biochemical data has amide. Biochemical investigations revealed gross already been given (Rodnight, 1959a). and persistent indicanuria and it was suggested by Rodnight and Mcllwain (1955), who studied this Case Reports guest. Protected by copyright. aspect of the illness, that the nicotinamide deficiency Family A.-This is the family of the boy (M.H.) whose might be due to a diversion of trytophan from its first attack of Hartnup disease has already been described by one of us (Hersov, 1955). The parents are not related. normal route of nicotinamide formation into that of The incidence of amino-aciduria in the family is given in indican formation. Table I. M.H. remains the only affected member, but it Shortly after the publication of these papers we has unfortunately been impossible to test the father (who were approached by Professor C. E. Dent, who deserted some years ago) and a brother on military expressed interest in the patient and with whose help service in the Far East. Further relatives have been we were able to show that the boy was an instance sought without success. of Hartnup disease, the hereditary pellagra-like M.H. was admitted to the Children's Department of disorder later reported in detail by Baron, Dent, the Maudsley Hospital in May, 1953, and discharged free Harris, Hart, and Jepson (1956). The syndrome of symptoms in July of that year. Shortly afterwards the these workers occurred in out of family moved to the north of England and contact with described by four the patient has been maintained through his school eight siblings of a marriage between first cousins and medical officer and general practitioner. He ceased was characterized by attacks of dermatitis and taking extra nicotinamide (prescribed on discharge) in cerebellar ataxia; it was also claimed that the October, 1955, and apart from a short spell of diarrhoea condition was probably associated with progressive in the summer of 1954 and a transient skin rash in the mental deterioration. Well-defined biochemical spring of 1957, he has remained in good health. He abnormalities were present in the affected siblings, completed schooling at a secondary modern school consisting of a constant renal aminoaciduria of without difficulty and is now apprenticed to a transport http://jnnp.bmj.com/ distinctive pattern and a high excretion of indican corporation as a mechanic. The last report we had from and other abnormal Our his general practitioner (Dr. C. Potts) was in April, 1958, tryptophan metabolites. when no -skin lesions or neurological or psychiatric patient was shown to have an aminoaciduria of abnormalities were found. exactly the same pattern, and although his clinical were in some no Family B.-The parents are not related and there are symptoms respects different, there is three daughters; the incidence of aminoaciduria is doubt that he has the same basic disorder. shown in Table I. The second daughter (E.) was first We were stimulated by this observation to search treated at the age of 18 years in 1949 by Dr. Denis Leigh on September 27, 2021 by for further cases of Hartnup disease amongst for a psychiatric disorder associated with pellargrous skin psychiatric patients. A female patient with similar lesions. Following publication of the paper by Baron symptoms, kindly brought to our notice by Dr. et al. (1956) we tested her urine for amino-acids and found Denis Leigh, was then found to have the biochemical her to be a case of Hartnup disease. Investigation of her family then showed that the eldest sister (J.) was also * Present address: Child Guidance Training Centre, Osnaburgh suffering from the disease, but there were no other Street, London. affected members. 40 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.23.1.40 on 1 February 1960. Downloaded from HARTNUP DISEASE IN PSYCHIATRIC PRACTICE 41 TABLE I resulted in the patient becoming markedly more cheerful INCIDENCE OF AMINO-ACIDURIA IN THE FAMILIES and active after 72 hours, followed by a decrease in the depression and depersonalization. Within a week the Subject Age (years) Aminoaciduria skin lesions had returned to normal, and she was also Family A - N free of psychiatric symptoms and somatic complaints. Fatner Not tested no Mother - Absent Prolonged exposure to sunlight then had further M., female 28 Absent harmful effect and she was discharged home fully R., male 26 Not tested S., female 23 Absent recovered in July, 1949, after three months in hospital. M., male 16 Present The patient has been followed up as an out-patient over Family B the past 10 years. In May, 1950, she suffered from weekly Father Absent fainting attacks which came on without warning and Mother ii Absent J., female 29 Present lasted one or two minutes. There was no tongue biting, E., female 27 Present incontinence, or muscular spasms, and no drowsiness or B., female 26 Absent confusion followed the attacks. Enquiry revealed no history of previous epileptic attacks and no family history E.-The patient is now a married woman of 27 years. of epilepsy. However, an electroencephalogram at this She was a healthy child apart from enuresis and tension time showed a number of non-specific anomalies at habits which ceased at the age of 6 years. Her parents varying frequencies of photic stimulation; coincidental noticed from an early age that her skin would easily injection of "metrazol" elicited a short burst of bilaterally redden and "peel" after exposure to sunlight. A severe synchronous 3 per second spike and wave. The fainting attack occurred during a summer holiday when she was attacks ceased with the administration of nicotinic acid 8 years old, the exposed areas of her body becoming red, (100 mg. daily). The patient remained well throughout painful, and later dark and scaly. There was another the summer of that year and did not develop any skin severe recurrence of the same skin lesions in the summer lesions. Nicotinic acid was discontinued in October, of 1948, the year before her admission to hospital. 1950. guest. Protected by copyright. She was a rather timid, dependent child, attended a In June, 1951, she had a similar fainting attack on one central school, and was generally average in class with no occasion, but again with no skin lesions or other symp- behaviour problems. She began work as a duplicating toms apart from irregular menstrual periods. Nicotinic machine operator and continued in this occupation until acid was again prescribed and continued throughout the she fell ill. At work she was popular, sociable, able, and winter. In the summer of 1952 she again had fainting easy to supervise. attacks once a week for four weeks, but they ceased when In October, 1948, she gradually experienced weakness "phenytoin" (grains thrice daily 1-5) and nicotinic acid and stiffness in the lower limbs and on several occasions (75 mg. daily) were given. "collapsed" while walking and had to be assisted. She In June, 1953, the patient developed a sore tongue, was able to continue work until February, 1949, when she angular stomatitis, and an erythematous scaly dermatitis complained of giddiness and double vision. This was of the exposed areas of the face and hands. There were followed by complaints of recurrent feelings of stiffness no complaints of fainting, depression, or depersonaliza- in the back and legs, which felt numb and tremulous after tion and the skin lesions responded rapidly to treatment exertion. She gave up work, but failed to improve. with nicotinic acid. In April, 1949, she became severely depressed with Since then the patient has remained free of symptoms suicidal preoccupation and complaints of inability to apart from mild anxiety and tension lasting a few months feel properly, and was admitted to the Maudsley Hospital. and related to marital difficulties. A neurological and Physical examination showed a fair-skinned, well- psychiatric examination in November, 1958, showed no nourished girl (7 st. 7 lb.) with no skin lesions or ab- abnormality. On this occasion psychological tests were normality in the central nervous system apart from brisk also carried out using the Wechsler intelligence scale reflexes. All other systems were normal. She was with the following results: full-scale I.Q., 95; verbal http://jnnp.bmj.com/ untidy in appearance, depressed, apprehensive, tense and I.Q., 102; performance I.Q., 88. The patient is now in tearful, expressing suicidal ideas. She described severe regular employment as a shop assistant. and persistent feelings of depersonalization. No J.-The patient, a single woman of 29 years, is an hallucinations or delusions were elicited; orientation, experienced typist holding a responsible position. She concentration, and memory were unimpaired. Her state is a reticent, unassertive person with few friends and showed no change during the following three weeks: she limited interests.
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