LETTERS TO THE EDITOR Byler’s syndrome EDITOR,—The report of Byler’s syndrome with raised sweat electrolytes in an Irish trav- eller kindred1 interests us, as we have observed raised sweat electrolytes in two members of the original Byler kindred who have Byler’s disease. Neither has cystic fibro- sis; both underwent liver transplantation in their second decade and subsequently devel- oped pancreatic disease. One has had recur- rent pancreatitis and the other has a fibrotic pancreas with exocrine insuYciency.2 In the children without Byler’s disease whom we attend, pancreatic disease after liver trans- plantation is not usual.Have aVected traveller children, particularly older ones, had pan- creatitis? We can provide additional information on the sister and brother with progressive famil- ial intrahepatic cholestasis and raised sweat electrolytes referred to by Bourke et al1 and described by Lloyd-Still3 4 (fig 1). Neither parent was of Irish or Amish background; the father (II.2) came of Norwegian and the mother (II.3) of Italian stock. At age 3.5 years, the boy (III.5) had normal serum ã-glutamyltranspeptidase activity (29 U/ml; expected, <40) and moderately raised cholesterol concentrations (8.0 mmol/l; ex- pected 3.9–6.5; determination at age 1 year,4 1.6) with marked hyperbilirubinaemia (458 µmol/l; expected, 1.7–20.5). Fasting serum bile acid concentrations were not measured but at age 1 year had been ‘markedly elevated’4; intense pruritus was present. Serum amylase and lipase activities were nor- mal. The (III.2) girl came to liver transplanta- tion aged 8 years and the boy 4.5 years. Both died of infection within two months of surgery. On light microscopy, findings in the native livers resembled those in the older traveller children1 and in the two Amish chil- dren who underwent hepatectomy.5 Coarsely granular bile like that seen in Byler’s disease (‘Byler bile’)5 was found on transmission electron microscopy (fig 2). Convergence of phenotypes leads us to believe that these children may have had a lesion at 18q21-q22, the Byler’s disease locus,6 to which the disorder in the traveller kindred also has been mapped.7 We would like to know what was seen if liver tissue from an aVected traveller child was examined by transmission electron microscopy. A S KNISELY Denver-Aurora Pathology Associates, 1719 East 19th Avenue, Denver,CO 80218,USA R M AGOSTINI B J ZITELLI* S A KOCOSHIS** Departments of Pathology,Pediatrics*,and Pediatric Gastroenterology**, Children’s Hospital of Pittsburgh, Pittsburgh,PA,USA J T BOYLE Division of Pediatric Gastroenterology, Rainbow Babies and Children’s Hospital, Cleveland,OH,USA Dr Bourke and Professor Drumm comment: We thank Dr Agostini and colleagues for their interest in our paper describing an Irish kin- dred with Byler syndrome.1 As yet, we have not examined liver tissue from the traveller kindred using transmission electron micros- copy. As these children likely will need further evaluation and/or transplantation in the coming years we will have the opportunity to undertake further studies including analy- sis of biliary bile acid content and examin- ation of biopsy samples for the presence of ‘Byler bile’. We are aware of the report of Knisely et al describing pancreatic disease in members of the original Amish kindred with Byler’s disease.2 Although we have not observed pancreatitis or evidence of pancreatic dys- function in the Irish traveller family with Byler’s syndrome, one of us (BB) has encountered a child with progressive familial intrahepatic cholestasis and chronic pancrea- titis at another institution (patient of E Rob- erts and R Superina, Hospital For Sick Chil- dren, Toronto). Whether this child has a mutation at 18q21-q22 is currently being evaluated. The presence of raised sweat electrolytes and pancreatitis in a subset of these children with Byler’s disease/syndrome is certainly intriguing and raises interesting questions about the function of the mutated allele at 18q21-22. Ongoing genetic studies of mem- bers of the original kindred and unrelated families such as this Irish family should soon provide answers to these questions. 1 Bourke B, Goggin N, Walsh D, Kennedy S, Setchell KDR, Drumm B. Byler-like familial cholestasis in an extended kindred. Arch Dis Child 1996;75:223-7. 2 Knisely AS, Boyle JT, Naylor EW, Klinger K, Freimer NB, Kocoshis S. Pancreatic dysfunc- tion in Byler disease. J Pediatr Gastroenterol Nutr 1995;21:328 (abstr). 3 Lloyd-Still JD. Familial cholestatic syndrome with elevated sweat electrolytes. In: Sturgess JM, ed. Proceedings of the 8th International Con- gress on Cystic Fibrosis. Toronto: Imperial Press, 1980:25a (abstr). 4 Lloyd-Still JD.Familial cholestasis with elevated sweat electrolyte concentrations. J Pediatr 1981;99:580-3. 5 Bull LN, Carlton VEH, Stricker NL, et al. Genetic and morphologic findings in progres- sive familial intrahepatic cholestasis (Byler dis- 1 2 1 3 4 75 8 9 10 32 4 5 6431 III II I 2 6 Figure 1 Pedigree of family with Byler disease-like progressive familial intrahepatic cholestasis described by Lloyd-Still.3 4 Figure 2 Transmission electron micrograph of coarsely granular bile, characteristic of bile from children with Byler’s disease,5 within canaliculus of liver obtained at hepatectomy in aVected boy (III.3);4% paraformaldehyde/0.5% glutaraldehyde in Swenson’s phosphate buVer,pH 7.3; OsO4/uranyl acetate/lead citrate (original magnification × 18 000). Archives of Disease in Childhood 1997;77:276–277276 o n A p ril 5 , 2 0 2 1 b y g u e st. P ro te cte d b y co p yrig h t. h ttp ://a d c.b m j.co m / A rch D is C h ild : first p u b lish e d a s 1 0 .1 1 3 6 /a d c.7 7 .3 .2 7 6 o n 1 S e p te m b e r 1 9 9 7 . D o w n lo a d e d fro m http://adc.bmj.com/ ease and Byler syndrome): evidence for hetero- geneity. Hepatology 1997;26:155-64. 6 Carlton VEH, Knisely AS, Freimer NB. Map- ping of a locus for progressive familial intrahe- patic cholestasis (Byler disease) to 18q21-q22, the benign recurrent intrahepatic cholestasis region. Hum Mol Genet 1995;4:1049-53. 7 Barton DE, McQuaid S, Bourke B, et al. Famil- ial progressive intrahepatic cholestasis (Byler disease): evidence that the disease haplotype in the Old Order Amish is also found in the Irish ‘traveller’ population. Am J Hum Genet 1996; 59:A248 (abstr). Intestinal neuronal dysplasia associated with cystic fibrosis EDITOR,—The association between cystic fibrosis and intestinal neuronal dysplasia (IND) has been rarely described.1 We report a case of full thickness, biopsy proved, IND type B of the ileum and colon associated with cystic fibrosis. The boy was born at full term to non-consanguineous parents. Because of obstructive symptoms, several resections were performed: 20 cm of distal ileum after birth; distal ileum and part of ascending colon at the age of 18 days; ileum, part of jejunum, and colon at the age of 2 months. A series of radiographs of the upper gastrointes- tinal tract series showed a normal duodenum at 16 months and no dilatations of the remaining intestinal tract. Contrast appeared in the rectum after 90 minutes. By histology, the proximal ileal tract had 6.25 neurons/mm of myenteric plexus, according to Smith’s method (normal values: 2–4),2 the ascending colon 16.0 neurons/mm, and the transverse colon 8 neurons/rnm. Acetylcholinesterase staining showed an increase of number of submucosal ganglia, neuronal heterotopy, and increase of positive fibres in circular muscular layer and lamina propria.3 NADPH-DH showed an increased number of neurons in myenteric and submu- cosal plexuses. The study with neurofila- ments (NF65, NN18) showed a normal maturity of neurons. The results of two sweat tests were abnormal.An homozygosity for the delta F508 mutation was demonstrated and both parents were carriers of the allele. It is possible that there is an NID-B determining gene linked to the cystic fibrosis transmem- brane conductance regulator locus for cystic fibrosis, localised on chromosome 7q. We suggest that intestinal neuronal dyspla- sia should be considered as an underesti- mated, underlying cause in patients with cystic fibrosis having functional small bowel dysmotility and obstruction leading to emer- gencies, such as meconium ileus in neonates or meconium ileus equivalent in children and adults. A TOZZI G ASCIONE* M L CARPENTIERI A STAIANO Departments of Paediatrics and Division of Paediatric Surgery*, University Federico II, Via S Pansini 5, 80131 Naples, Italy 1 Wildhaber J, Seelentag WKF, Spiegel R, Schoni MH. Cystic fibrosis associated with neuronal intestinal dysplasia ype B: a case report. J Pedi- atr Surg 1996;31:9411-4. 2 Smith VV. Intestinal neuronal density in childhood: a baseline for objective assessment of hypo- and hyperganglionosis. Pediatr Pathol 1993;13:225-37. 3 Milla PJ, Smith VV. Intestinal neuronal dyspla- sia. J Pediatr Gastroenterol Nutr 1993;17:356-7. Legislation and drug trials EDITOR,—In their recent leader, Walsh and Drumm point out important diYculties facing paediatricians wishing to conduct intervention trials where the aim is to prevent disease in children (or anyone incapable of giving fully informed consent) in Ireland.1 It is worth pointing out that the Irish legislation that prevents such studies thereby prevents all vaccine studies in children from being conducted in that country. Vaccines against Haemophilus influenzae type b and more recently acellular vaccines against pertussis have been licensed and introduced in Ireland on the basis of immunogenicity and eYcacy studies done elsewhere. While it is not neces- sary for each vaccine to be studied in every country, there is a clear need for all countries to be able to contribute clinical studies particularly as the number of new antigens and combinations grows. It is to be hoped that the current stranglehold on research into child health in Ireland is loosened in the near future. ADAM FINN Department of Paediatrics, University of SheYeld, SheYeld Children’s Hospital, SheYeld S10 2TH 1 Walsh D, Drumm B. Legislation and drug trials. Arch Dis Child 1997;76:296-7. Situs inversus and left sided pyloric tumours EDITOR,—The case report by Harrington et al1 reminded me of the procedure to examine for a pyloric tumour taught by Dr M J Simp- kiss, based on an identical case he had seen decades previously. Namely, define the apex beat before examining the abdomen. This combination will occur again, just like the case of ‘The glass eye...’.2 RICHARD SPORIK Institute of Respiratory Medicine, University of Sydney,NSW 2006, Australia 1 Harrington B, Chambers T, Grier D. A diagno- sis obscured:pyloric stenosis with situs inversus [letter]. Arch Dis Child 1997;76:385. 2 Gordon RM, Greene JM, Kassirer JP. Solution to a ‘medical mystery’[letter]. N Engl J Med 1997;336:1393-4. Head lice in schoolchildren EDITOR,—I am grateful to Ibarra and Hall for reviewing a common problem in general practice.1 I recently performed a Medline search of the literature regarding the role of hairdressers and head lice. To my concern no references existed and my personal experience compounds my view that some gentlemen’s hairdressers do not wash, let alone sterilise their ‘tools’ or drapes between customers. Therapy has an important role in the eradication of head lice, but there is a more important public health issue in relation to prevention. RODGER CHARLTON The Surgery,Fentham Hall, Marsh Lane,Hampton-in-Arden, Solihull,West Mdlands B92 0AH 1 Ibarra J, Hall DMB. Head lice in schoolchil- dren. Arch Dis Child 1996;75:471-3. Letters 277 o n A p ril 5 , 2 0 2 1 b y g u e st. P ro te cte d b y co p yrig h t. h ttp ://a d c.b m j.co m / A rch D is C h ild : first p u b lish e d a s 1 0 .1 1 3 6 /a d c.7 7 .3 .2 7 6 o n 1 S e p te m b e r 1 9 9 7 . D o w n lo a d e d fro m http://adc.bmj.com/