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Early Diagnosis of Severe Combined Immunodeficiency Syndrome

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Early Diagnosis of Severe Combined Immunodeficiency Syndrome 260 Archives ofDisease in Childhood 1994; 70: 260-263 ORIGINAL ARTICLES Arch Dis Child: first published as 10.1136/adc.70.4.260 on 1 April 1994. Downloaded from Early diagnosis of severe combined immunodeficiency syndrome R A Hague, S Rassam, G Morgan A J Cant Abstract treatment die within the first year of life from Infants with severe combined immuno- overwhelming infection.' The prognosis of deficiency syndrome (SCIDS) have a children with SCIDS has been transformed by greatly improved prognosis if diagnosed bone marrow transplantation and data from a and treated before they develop over- European collaborative study of affected whelming infection. Clinical and labora- infants (in which Newcastle upon Tyne and tory data on 45 patients with SCIDS were London are the participating centres in the retrospectively reviewed to assess the UK) have shown 97°/0 long term survival for value of absolute lymphocyte counts in recipients ofHIA identical sibling marrow and making an early diagnosis. Ninety infants 52% survival for recipients of HLA mis- matched for age, sex, and presenting matched (haploidentical) marrow from a symptoms were used as controls. Thirteen parent.2 The survival rate for infants trans- (29%) infants with SCIDS were diagnosed planted after 6 months of age is only 45%/o, at birth as previous siblings had been however, compared with 70°/ in younger affected; 32 (71%) were diagnosed after children. Although facilities for bone marrow the development of symptoms. Eighteen transplantation for the treatment of SCIDS (56%) of these remained undiagnosed are available within the UK, many affected until after 6 months of age. The first children without a family history are older than symptoms occurred at a median of 5 6 months of age at referral, or are terminally ill weeks 1 to 8 and the with (range day months) overwhelming infection, making trans- http://adc.bmj.com/ first admission to hospital was at 4 months plantation a risky procedure. (range 1 week to 16 months). Symptoms The incidence of SCIDS is one in 66 000 live included respiratory infection (91%), births in most parts of the world,3 6 although it vomiting and diarrhoea (81%), failure to is higher in some populations.7 Thus in thrive (88%), candidiasis (50°/0), and skin paediatric practice in the UK a case will be lesions (28%). The mean lymphocyte encountered only rarely. Early symptoms and count was 171X109/1 compared with signs can be non-specific and only after a 792X iO1/l in controls. Excluding one child number of infective episodes, or an infection of on September 25, 2021 by guest. Protected copyright. with Omenn's syndrome (lymphocyte unusual severity, may immunodeficiency be count 23-3X 109I), all symptomatic infants suspected. A full blood count with differential with SCIDS had lymphocyte counts less white blood cell count is usually performed in than 2-8X 1o9/ at presentation. The infants with an infection severe enough to merit median delay between the first abnormal admission to hospital. Previous workers have lymphocyte count and diagnosis was seven reported conflicting data on the proportion of weeks (range one day to 13 months). infants with SCIDS who are lymphopenic.81l Twenty eight (88%) of 32 infants would We have therefore documented the presenting have been diagnosed before 6 months of clinical features of such infants and studied the Department of Paediatric age if investigated after the first low usefulness oftheir absolute lymphocyte count in Inmmunology, lymphocyte count. These data indicate alerting a paediatrician to the possibility of Newcastle General that low lymphocyte counts are predictive SCIDS at an early stage when immediate Hospital, Newcastle upon Tyne ofSCIDS. Paediatricians are urged to pay treatment would greatly improve the prognosis. R A Hague attention to the absolute lymphocyte A J Cant counts in all infants in whom a full blood count is performed. Those with Methods Department of lympho- Immunology, Institute cyte counts persistently less than 2-8X 109/1 Patients with SCIDS seen in Newcastle upon ofChild Health, should be investigated for SCIDS. Tyne, London, and Edinburgh were identified London (Arch Dis Child 1994; 70: 260-263) from hospital records. Clinical and laboratory S Rassam G Morgan data on each child were reviewed retrospec- tively and for those referred from elsewhere Correspondence to: Dr A J Cant, Department of Severe combined immunodeficiency syndrome additional data about the initial presentation Paediatric Immunology, (SCIDS) is a heterogeneous group of inherited were sought from the referring hospital. Two Newcastle General Hospital, Westgate Road, Newcastle disorders characterised by the failure ofcellular control groups were identified among infants upon Tyne NE4 6BE. and humoral immunity. Children present with presenting to Newcastle General Hospital. Accepted 5 December 1993 recurrent or persistent infections and without The first group consisted of infants matched Early diagnosis ofsevere combined immunodeficiency syndrome 261 14 ment of symptoms was 5 weeks, the earliest 12 being at 1 day of age. Only one child, who 10 first became unwell at 8 months, had been Arch Dis Child: first published as 10.1136/adc.70.4.260 on 1 April 1994. Downloaded from cn C.) 8 asymptomatic at 6 months of age. 0 6 The median age on first admission for 0 symptomatic infants was 4 months (range 1 z week to 16 months) (fig 2). Respiratory infec- 2 tion (cough and wheeze, or less commonly 0 2 3 4 5 6 7 8 pneumonia), seen in 22 infants, was the most Age (months) common presenting symptom. Nine presented with and with Figure 1 in index vomiting diarrhoea, eight children. candidal infection, six were failing to thrive, and two had skin sepsis. Six children had only one of these symptoms by the time they were for age and first presenting symptom (for first admitted to hospital, eight had two, 10 example, chest infection, wheeze, diarrhoea, had three, eight had four, and one had all five failure to thrive) with the infants with SCIDS (one was admitted for an unrelated cause). presentinig with infection. The second control The diagnosis of SCIDS was not made until a group cc)nsisted of uninfected term infants median age of 7 months (range 4 weeks to 16 undergoi.ng blood counts either before an months). By the time all infants had at least operatiori or for the investigation of jaundice, two symptoms and most were failing to thrive. and was imatched with the infants with SCIDS The age of onset of the commonly observed who wer*e diagnosed at birth because of a symptoms and their frequency among the family hiEstory of the syndrome. group is shown in the table. White cell counts in index cases and controls Twenty eight (88%) of the 32 infants had a were me-asured by an automated Coulter 'routine' blood count checked at the time of method and blood was also filmed for a the first hospital admission, the count not differentiial white cell count. Statistical analysis being checked until later in the other four of the two groups used Student's t test. infants. The median age for the first blood count was 4 months (range 1 week to 11 months). The mean total white cell count in Results these infants was in the normal range at Forty fivee children with SCIDS were identified 8 29X 109/l and did not differ significantly and each child was matched with two control from the controls (9 25 X 109/1): only five were children from the appropriate group (90 leucopenic (white cell count <4 OX 109/1) and children) Thirteen (29%) infants were seven had a white cell count greater than http://adc.bmj.com/ diagnosed at or around the time of birth and 11 X 109/l. In 44 infants with SCIDS, excluding were asyimptomatic (all had a family history of the one child with Omenn's syndrome a previously affected sibling). Thirty two (lymphocyte count 23 4X 109/l), the mean (71%/o) c:hildren with no family history of lymphocyte count was 1 72X 109/1 compared SCIDS Nwere diagnosed once symptoms had with 6e02 x 109/1 in controls (p<O*00 1). developed. Of these only 14 (44%) were Figure 3 illustrates the distribution of diagnoseid before the age of 6 months. As lymphocyte counts in index and control shown in fig 1, the median age for the develop- children. All symptomatic infants except the on September 25, 2021 by guest. Protected copyright. one with Omenn's syndrome had lymphocyte counts less than 2 8X 109/1 and their lympho- penia persisted on repeat sampling. Five con- trol children also had lymphocyte counts <2 8X 109/1 on initial presentation, but in these a) the counts were normal on repeat testing. In C.)a) the index children lymphocyte counts tended to co decrease with time, despite the children being 0 0 treated for their presenting infection. For the z symptomatic children the false positive rate for SCIDS among children with a lymphocyte count <2 8X 109/1 was 8%, with a positive pre- 1 3 5 7 9 dictive value of 86% and a negative predictive 24 6 8 1011 1214162131415161718 A4g6e8Age (months)10onths) valuepredictiveof 100%.valueForwasall the93%childrenand thethenegativepositive Figure 2 Age offirst hospital admission for symptomatic predictive value was 93%/o. index child? Although the most rapid diagnosis after the Frequency and median (range) age ofonset ofcommonly observed symptoms in index first blood count was made the next day, the children median delay between the first low lymphocyte count and diagnosis was seven weeks. One No (% of childre°) Median (range) age of onset child was only diagnosed 13 months later. Only four children did not receive a blood Respiratory infection 30 (941) 10 Weeks (1 day to 9 months) count in the first six months of life, and so Vomiting/diarrhoea 26 (81I) 4 Months (1 week to 14 months) Candidal infection 15 (477) 3 Months (2 weeks to 10 months) 28 could have been diagnosed before this Failure to thrive 28 (88 10 Weeks (1 to 11 months) Skin sepsis 9 (2E3)1) 3 Months (1 to 8 months) time if investigated after the first abnornal lymphocyte count.
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