Auditory brainstem response in children with total intestinal aganglionosis

(Thr2184Ala) and G5380A (Vall732Met), represented neutral polymorphisms. When 17 APC-resistant and 11 normal relatives of 5 symptomatic probands were tested,

only the APC-resistant relatives had the heterozygous Arg506Gln mutation whereas all normal relatives had only the normal sequence, showing that this mutation cosegregated with APC resistance. Since the peptide bond between Arg-506 and Gly-507 is the first bond cleaved by APC during inactivation of factor Va, the observed resistance of Arg506Gln factor Va to APC inactivation5 is easily rationalised on a biochemical level as is the dominant transmission of APC resistance. ’’" The 8 APC-resistant probands included 7 whites (2 Ashkenazi Jews and 5 probands of varying European origin) and 1 African American. Thus the Arg506Gln mutation is present in different ethnic groups, and since all 8 tested APC-resistant probands are heterozygous for Arg506Gln, we speculate that most APC-resistant subjects will have this common Arg506Gln factor V mutation. We propose that thrombophilia associated with APC resistance caused by factor V mutations be designated "thrombophilia V". Judith S Greengard, Xi Sun, Xiao Xu, Jose A Fernandez, John H Griffin, Bruce Evatt Scripps Research Institute, La Jolla, CA 92037, USA; and Centers for Disease Control and Prevention, Atlanta, GA

1-111 and III-V intervals remained within normal limits. The abnormality recorded was consistent with an inner-ear deficiency that developed from an impaired distribution of spiral ganglion cells. These results indicate that the inner ears may also be affected in patients with very severe forms of intestinal aganglionosis, possibly because of a common embryonal defect of neural-crest-derived cells. We believe that these patients show extensive variations in neural-crest-cell disorders, and suggest the need for auditory brainstem response screening in these children.5 Because of progress in treatment by total parenteral nutrition and intestinal transplantation, these patients may have longer lives than

previously. Takashi Shimotake, Naomi Iwai Surgery, Children’s Research Hospital, Kyoto Prefectural University of Medicine, Kamigyo, Kyoto 602, Japan Division of

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Dahlbäck B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci USA 1993; 90: 1004-08. Koster T, Rosendaal FR, de Ronde H, Briët E, Vandenbroucke JP, Bertina RM. Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study. Lancet 1993; 342: 1503-06. Griffin JH, Evatt B, Wideman C, Fernández JA. Anticoagulant protein C pathway defective in majority of thrombophilic patients. Blood 1993; 82: 1989-93. Svensson PJ, Dahlbäck B. Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 1994; 330: 517-22. Sun X, Evatt B, Griffin JH. Blood coagulation factor Va abnormality associated with resistance to activated protein C in venous thrombophilia. Blood 1994; 83: 3120-25.

Auditory brainstem response in children with total intestinal aganglionosis SiR-Genetic mutations in patients with multiple endocrine neoplasia type 2A and familial Hirschsprung’s disease have been reported in the Ret proto-oncogene of chromosome 10 (lO.qll.2).’ Eng and colleagues (March 19, p 709) reviewed the genetic abnormalities in hereditary diseases that are intimately associated with neural-crest-derived cells. We have examined auditory function in children with total intestinal aganglionosis, an extreme form of a neural crest migration disorder, to see whether acoustic spiral ganglion cells are also affected.’ We recorded auditory brainstem responses in three children with total or near-total intestinal aganglionosis who had undergone surgery as neonates for severe gut motility disorders. No aminoglycosides had been given to these children. In a 2-year-old child whose most distal ganglion cells were found 5 cm from the ligament of Treitz, the auditory brainstem response showed a normal physiological pattern. The second patient, aged 3 months, had ganglion cells up to the second portion of the duodenum. The thresholds of auditory brainstem response were mildly increased in this patient. The third patient was 5 months old and had no ganglion cells identified, even in the stomach. The thresholds in this patient were increased bilaterally and waves I, III, and V were substantially delayed, although the

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Mulligan LM, Kwok BJ, Healey CS, et al. Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature 1993; 363: 458-60. Romeo G, Ronchetto P, Luo Y, et al. Point mutations affecting the tyrosine kinase domain of the RET proto-oncogene in Hirschsprung’s disease. Nature 1994; 367: 377-78. Edery P, Lyonnet S, Mulligan LM, et al. Mutations of the RET proto-oncogene in Hirschsprung’s disease. Nature 1994; 367: 378-80. Doel MS. The neural crest and the acoustic ganglion. J Embryol Exp Morph 1967; 17: 533-41. Cox C, Hack M, Aram D, et al. Neonatal auditory brainstem response failure of very low birth weight infants: 8-year outcome. Pediatr Res 1992; 31: 68-72.

Varicella-zoster vaccination for health workers

care

SiR-In their April 16 commentary Watson and Starr recommend a universal childhood varicella vaccine immunisation programme both to prevent illness and as an economic saving in terms of diminishing hours parents spend away from work looking after ill children. Adult chickenpox also has important health and economic implications, especially if the adult concerned is a health worker involved in the care of immunocompromised

patients.

managed on two occasions immunosuppressed patients exposed to chickenpox in staff on a haematology unit. In the first episode, the index case was a doctor who had spent his childhood in the tropics. During his prodromal illness, 50 patients were identified as having been exposed to varicella-zoster virus (VZV), including patients undergoing chemotherapy (n= 11) or bone marrow transplantation for malignant haematological disease (4). 6 patients needed zoster hyperimmune globulin and 15 received prophylactic acyclovir. In the second episode, the Over the past year,

we

have

index case was a doctor who had spent his childhood in the UK. On this occasion 38 patients were exposed to VZV, of whom 13 were undergoing chemotherapy and 5 had received a bone marrow transplant. 5 patients needed zoster hyperimmune globulin and 10 are receiving prophylactic acyclovir. The cost of infection control measures adopted during the first episode, including follow-up of staff and patients, was about 5435. The second episode is still in progress. VZV outbreaks among staff and patients in hospital have been well described.’ Hospital workers from the tropics may be at higher risk of chickenpox.2 Recent data suggest that there is an increase in adult disease in the UK. One would therefore expect an increase in infections in health care

workers with

subsequent implications for nosocomial spread.