856

pools by deflecting such donors from whole blood to plasma donation. This could, at least theoretically, jeopardise the efficacy of current virus-inactivation methods. Moreover, the introduction of anti-HCV positive plasma donations into the operation of blood centres could increase the risk of error and contamination. Pending the production of proof of the invalidity of the above arguments anti-HCV positive plasma should be excluded from fractionation pools. However, studies on the presence and potency of neutralising anti-HCV in such positive plasma donations and, eventually, clinical trials of the efficacy of specific high titre anti-HCV Ig in the treatment of HCV infections do seem warranted. BAHMAN HABIBI National Blood Transfusion Centre, 75571 Paris, France MICHEL GARRETTA

HJ, Purcell RH, Shih JW, et al. Detection of antibody to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A non-B hepatitis. N Engl J Med 1989; 321: 1494-500. 2. American Association of Blood Banks/American Red Cross/Council of Community Blood Centers. Guidelines for planning the implementation of anti-HCV testing of blood and components for transfusion. Feb 8, 1990. 3. Maisonneuve P, Guerois C, Noel L, et al Anti-HCV antibodies in French haemophiliacs only substituted with factor VIII SD concentrates. In: First Ortho Diagnostics International Meeting on Hepatitis C Virus. (Sept 14-15, 1989, Rome); abstr. 4. First Ortho Diagnostics International Meeting on Hepatitis C Virus. (Sept 14-15, 1989, Rome); abstr. 5. Nihon University International Symposium on non-A non-B hepatitis and blood borne infectious disease. (Sept 27-30, 1989, Tokyo); abstr. 1. Alter

Mutation of aldolase B genes in hereditary fructose intolerance SIR,-Dr Cross and colleagues (Feb 10, p 306) describe three mutations in patients with hereditary fructose intolerance. We are currently examining the frequency of the mutation A149P in our clinic population, with a view to establishing less invasive diagnostic techniques. We have completed studies on four kindreds (six patients). The procedure used is as described by Cross et al/ with minor modifications. Exon 5 of the aldolase B gene is amplified by means of the polymerase chain reaction, and the A149P mutation is detected by the restriction enzyme site (AhaII) it creates. All four kindreds were of Anglo-Saxon origin. The diagnosis was confirmed by either intravenous fructose tolerance test or enzymatic assay on liver biopsy. Four patients in two kindreds were homozygous for A 149P, and two patients in the other two kindreds were heterozygous for that mutation-ie, all our patients carried at least one A149P allele. We believe that its presence in a child with a characteristic history, in view of the low carrier frequency, would be sufficient for diagnosis in our population. However, the use of several specific oligonucleotide probes will enable definitive diagnosis in more patients, and will prove especially useful in individuals in whom the history is not characteristic (eg, in infants with unexplained liver disease). Department of Gastroenterology, Royal Alexandra Hospital for Children, Camperdown, NSW 2050, Australia; and Clinical Immunology Research Centre, University of Sydney, Camperdown

M. DE SOUZA R. LINDEMAN F. VOLPATO R. J. TRENT R. KAMATH

10% represented 8 people, only 1 of whom was a carrier. The data showed that most carriers (36 of 37) remembered the pertinent facts. Ten Kate and Tijmstra interpreted the data selectively and to the discredit of carriers. Holtzmandescribes our screening programme’in high schools with an exclamation point and the word coercion to describe the high participation rates. Readers with a different point of view will find alternative explanations in the articles. They will also discover that high school students in Montreal combined opportunity and self-interest to improve their awareness, understanding, and knowledge about their own genetic risk. Is that bad? Why does their apparently positive experience invite negative opinion? Meanwhile, we and others’ recognise that differences of opinion are the nonn among medical

geneticists.

De Belle Laboratory for Biochemical Genetics, Montreal Children’s Hospital, Montreal, Quebec H3H 1P3, Canada

CHARLES R. SCRIVER CAROL L. CLOW

CL, Cartier L, Scriver CR. A private view of heterozygosity eight-year follow-up study on carrier of the Tay-Sachs gene detected by high school screening m Montreal. Am J Med Genet 1984; 18: 769-78 2. Holtzman NA. Proceed with caution: predicting genetic risks in the recombinant DNA era Baltimore: Johns Hopkins University Press, 1989: 217-18. 3. Scnver CR, Bardanis M, Cartier L, Clow CL, Lancaster GA, Ostrowsky JT. &bgr;-thalassemia disease prevention: genetic medicine applied. Am J Hum Genet 1984, 1. Zeesman S, Clow

36: 1024-38. DC, Fletcher JC. An international survey of attitudes of medical geneticists toward mass screening and access to results. Publ Health Rep 1989; 104: 35-44

4. Wertz

Anti-glomerular-basement-membrane disease after lithotripsy SIR,-Extracorporeal shock wave lithotripsy (ESWL) is an effective non-invasive treatment for renal calculi, but it carries a risk of renal damage.’ We report on a 67-year-old man treated by ESWL (Dornier HM3) in March, 1989, with 1800 shocks plus 1350 shocks 10 days later, for a single stone in his left kidney; his right kidney had been removed in 1975 for pyonephrosis. Before treatment the patient’s serum creatinine level was slightly increased (105 Nrmol/1) and it rose transiently after ESWL. 7 months later, the patient was admitted for fever and left-sided loin pain without any sign of pulmonary involvement. All bacteriological and virological tests proved negative. Intravenous pyelography did not suggest any obstruction. His serum creatinine rose within 10 days from 147 to 1074 umol/1, and haemodialysis was required (figure). Renal biopsy revealed burst glomeruli with complete necrosis of the flocculus and disruption of Bowman’s capsule, surrounded by cellular crescents and multinucleated giant cells; diffuse interstitial cell infiltration was present. Immunofluorescence demonstrated linear fixation of anti-IgG and anti-C3 along the glomerular basement membrane (GBM). Circulating anti-GBM antibodies were detected by indirect immunofluorescence and ELISA. All other immunological tests were normal. The patient had stopped smoking 6 years ago earlier. He had no history of recent infection or injury and had not received immunosuppressive therapy. A search for GBM antibodies in a

NCP, Tolan DR, Cox TM. Catalytic deficiency of human aldolase B in hereditary fructose intolerance caused by a common missense mutation. Cell 1988;

1. Cross

53: 881-85.

Carrier

screening for Tay-Sachs disease

SIR,-Our follow-up study1 of screening for Tay-Sachs carriers high school students continues to elicit surprising opinions and interpretations. Dr Ten Kate and Dr Tijmstra (Oct 21, p 973), in their analysis of carrier screening for cystic fibrosis, state that screening in adolescence carries the danger that those screened will forget the results, and they cite our finding that 10% did so in a Tay-Sachs screening programme in Canada. They did not say that among

Course of plasma creatinine concentration and of GBM antibodies after lithotripsy.

857

stored

serum

sample obtained

3

days

before

lithotripsy

was

negative. His HLA phenotype was B7 DR2. More and

more

publications mention the

emergence of

extrarenal or renal lesions after ESWL, including release of renal tubular enzymes. Histological and ultrastructural evaluation after ESWL revealed alterations in the endothelium and glomerular and haemosiderin accumulation in tubular cells .2 A in dogs has suggested a time-course for the histological study changes: bleeding foci with complete tissue destruction and rupture of the glomerular capsule, veins, and arteries are noted 1 hour after ESWL, tubular cell vacuolisation is seen after 24 hours, and interstitial fibrosis develops after 3 months.3 Alterations to the structure of GBM might favour the exposure of the globular domain NC1 of collagen IV, which contains the Goodpasture antigen. The GBM antigen exposed or released after lithotripsy could precipitate Goodpasture and anti-GBM diseases in genetically predisposed patients. Patients treated by ESWL should be considered at risk of autoimmune renal diseases, and a search for GBM autoantibodies could help in the management of acute renal failure after ESWL.

epithelium

Department of Nephrology, Hôpital Necker, 75015 Paris, France

V. GUERIN C. RABIAN L. H. NOEL D. DROZ C. BARON F. LALLEMAND P. JUNGERS

1. Williams CM, Thomas WC. Permanently decreased renal blood flow and hypertension after lithotripsy. N Engl J Med 1989; 321: 1269-70. 2. Rigatti P, Colombo R, Centemero A, et al. Histological and ultrastructural evaluation of extracorporeal shock wave lithotripsy-induced acute renal lesions: preliminary report. Eur Urol 1989; 16: 207-11. 3. Jaeger P, Redha F, Uhlschmid G, Hauri D. Morphological changes in canine kidneys following extra-corporeal shock wave treatment. Urol Res 1988; 16: 161-66.

Acute non-lymphocytic leukaemia versus transient leukaemoid reaction in fetuses with Down syndrome SIR,—Dr Zerres and colleagues (Jan 13, p 117) describe the prenatal diagnosis of acute non-lymphocytic leukaemia in two fetuses with

syndrome. The association between Down syndrome

and congenital acute leukaemia is well established.1 The differential diagnosis of congenital leukaemia includes a poorly understood myeloproliferative disorder in fetuses and newborn babies with Down syndrome, known as a transient leukaemoid reaction. We report our experience and offer some words of caution.2 Patient 1. Down syndrome (47XY, + 21) and hydrops fetalis was diagnosed by routine sonography in the 27th week of gestation. Soon afterwards the fetus died. Necropsy showed leukaemic blood indices, with blastic leucocytosis, anaemia, thrombocytopenia, and leukaemic infiltrations of the pericardium and the myocardium. Hydrops was attributed to the leukaemic cardiac infiltrations and not to haemolytic anaemia or a detectable infectious disease. Patient 2. Routine fetal ultrasonography at 31 weeks’ gestation had shown a pericardial effusion, slight hepatosplenomegaly, enlarged kidneys, and ascites but no signs of hydrops of the fetus or the placenta. Cytogenetic analysis of fetal blood indicated Down syndrome (47XY, +21) without any additional chromosomal abnormalities. Haematology showed a leukaemic picture with 70 000/ul atypical blasts, pronounced fetal anaemia (Hb 10-6 g/dl), and thrombocytopenia. Immunophenotyping of the blasts showed CD 33, CD 22; TdT was positive. At birth (37 weeks) this picture was unchanged and bone marrow was densely populated by a monomorphic cell population consisting of myeloid blasts. The baby had the same organ involvement as patient 1 and leukaemic skin infiltrations. However, signs of disease disappeared spontaneously within the first 8 weeks of life, blood indices returned to normal. The child is now 12 months old and doing well. Patient 3. Because of premature labour at 37 weeks’ gestation the fetus was investigated by sonography and proved to have a pericardial effusion, ascites, and a slight hepatosplenomegaly. Karotype was 47XY, + 21; the fetus had a pronounced anaemia (Hb 102 g/dl), thrombocytopenia 60 000/1, and 78 000/fil atypical

Down

myeloid blasts. Intrauterine infections were ruled out. The blast cells expressed CD 33 and CD 34 on their surface and were TdT positive; cells carried no additional chromosomal marker. The leukaemic blood picture resolved spontaneously within the first 10 weeks of life. The child is now eight months old and doing well. In view of the favourable course in patients 2 and 3

we

would be

very cautious about diagnosing congenital leukaemia in a child with

syndrome either during pregnancy or after birth. It is impossible to differentiate true congenital leukaemia from transient leukaemoid reaction by means of clinical signs and cell marker analysis.3 The occurrence of an additional marker chromosome in Zerres and colleagues’ patient 1 is of great importance since it suggests that a prominent monoclonal myeloid cell proliferation can disappear spontaneously in newborn babies with Down syndrome. One could further postulate that the described disorder might be in line with Bolande’s4 notion of benignity of malignant tumours in early life. Our observations emphasise the need to withhold any specific therapy in these conditions -during their prenatal and postnatal course. These children must be followed up carefully since they may have an increased risk of true leukaemia.’’ Down

University Children’s Hospital, Department of Paediatrics II, Ulm

G. GAEDICKE E. KLEIHAUER

Department of Gynecology and Obstetrics, University of Ulm, 7900 Ulm, West Germany

R. TERINDE

Eys J, Flexner JM. Transient spontaneous remission in a case of untreated congenital leukemia. Am J Dis Child 1969; 118: 507-14. 2. Gaedicke G, Terinde R, Kleihauer E. Akute Leukamie versus leukamische Reaktion. Intrauterine Diagnose bei einem Kind mit Morbus Down. Mschr Kinderheilk 1989; 137: 529. 3. Weinberg AG, Schiller G, Windmiller J. Neonatal leukemoid reaction. Am J Dis Child 1982; 136: 310-11. 4. Bolande RP. Benignity of neonatal tumors and concept of cancer repression in early life. Am J Dis Child 1971; 122: 12-24. 5. Lin Hu P, Menaka H, Lim KH, Yong HS. Congenital leukemoid reaction followed by fatal leukemia. Am J Dis Child 1980; 134: 939-41. 1. van

Cromoglycate treatment of patient with hyperimmunoglobulinaemia E syndrome SiR,—The hyperimmunoglobulinaemia E syndrome (HIE) is

a

immunodeficiency disorder characterised by increased serum IgE, sinopulmonary infections, cold skin abscesses, chronic pruritic dermatitis, and growth retardation.1,2The most successful treatment is long-term antibiotic therapy with drainage of abscesses. We describe here a patient with HIE syndrome whose susceptibility to infection ceased when he was taking disodium cromoglycate (DSCG). Immunological abnormalities improved at rare

the same time. The patient, now aged 7, had been referred at the age of 3 years with a history of eczema, large scalp abscesses associated with Staphylococcus aureus, chronic otitis media with purulent discharge, and cold abscesses, eventually diagnosed as being due to staphylococcal infection. This was followed by recurrent pneumonia, and between the ages of 6 and 7 he had been admitted to hospital several times with severe pneumonia. During the past 4z years he had put on only 1-5 kg. He also had a history of fractures, candidiasis of the nails, mouth, and skin, and chronic pruritic eczematoid rashes that sometimes flared up despite use of an antibiotic/steroid ointment. Eosinophils made up 6-12% of his white-cell count. IgE levels were 9800 IU/ml (normal below 250) at age 3, rising to 43 000 IU/n-d just before treatment with DSCG at age 7. Antigen-specific IgE was moderately increased, specially against candida and food allergens, as would be expected in atopic disease. He had an antistaphylococcal IgE of 8-9% (normal 0-2-0-6%). IgA was normal (100 mg/dl) but IgM (300 mg/dl), IgG (2000-2300 mg/dl at age 7), and IgD (100-150 mg/dl; normal below 9) were all increased; serum C3, C4, and CH were normal. Neutrophil chemotaxis was normal. T and B cell counts were 84% and 11 %, respectively. T-cell subsets were normal (CD3 + 77%, CD4+ 47%, CD8+24%, CD2+ 78%), the one abnormality