Manganese deposits in patients with biliary atresia after hepatic porto-enterostomy

doi:10.1016/S0022-3468(00)90212-4

Journal of Pediatric Surgery

Volume 35, Issue 3, March 2000, Pages 450-453

https://doi.org/10.1016/S0022-3468(00)90212-4 Get rights and content

Abstract

Purpose: The aim of this study was to determine if there is latent manganese toxicity in patients with biliary atresia. Methods: Fifteen children with biliary atresia were examined postoperatively with regard to whole-blood manganese levels using brain magnetic resonance imaging (MRI) and I-123 iodoamphetamine (IMP) per rectal portal scintigraphy. Results: Nine (60%) of the 15 had high whole-blood manganese levels (mean, 4.1 μg/dL; range, 1.2 to 9.6; normal, 0.5 to 2.5), and these 9 had hyperintense globus pallidus on T1-weighted images, with no corresponding signal change in T2 sequences. I-123 IMP per rectal portal scintigraphy was done for 13 patients to evaluate portosystemic shunt flow. 12 (92%) of these patients had an increased flow. Mean shunt ratio was estimated to be 41% (range, 0.6 to 98; normal, <5%). Encephalopathy was evident in only 1 patient. Conclusions: Some patients with biliary atresia in the postoperative period have manganese deposits in globus pallidus on T1-weighted images and high whole-blood manganese levels, possibly caused by increased portsystemic shunt, and a latent or subclinical encephalopathy is also present. J Pediatr Surg 35:450-453. Copyright © 2000 by W.B. Saunders Company.

Section snippets

Materials and methods

Fifteen Japanese children with biliary atresia underwent follow-up in the Department of Pediatric Surgery, Kumamoto University Medical School. All had been treated using the Kasai procedure (hepatic portoenterostomy). The median age at the time of diagnosis and surgery was 1.6 months (range, 1 to 3 months; Table 1).Informed consent was obtained from a parent or guardian of each patient; the consent included permission for oral sedation. The median age of the children was 7 years at the time of

Results

Nine (60%) of the 15 children had high whole-blood manganese levels (mean, 4.1 μg/dL; range, 1.2 to 9.6; normal, 0.5 to 2.5; Table 1) and 6 of the 9 patients had no jaundice. Of the 9 with high whole-blood manganese levels, all had hyperintense globus pallidus on T1-weighted images, without a corresponding signal change on the T2 sequences (Fig 1).

. Axial T1-weighted MRI in the case 12 patient showing abnormal increased signal intensity in the region of the globus pallidus (arrows).

In 2 of the

Discussion

Pallidal signal hyperintensity on T1-weighted MRI has been reported to occur in a majority of cirrhotic patients.⁶ There is substantial evidence to suggest that manganese deposition is the cause of pallidal MRI signal hyperintensity in cirrhotic patients.⁷ Devenyi et al⁸ reported a patient with decompensated cirrhosis caused by Alagille syndrome, and pallidal signal hyperintensity on MRI was increased as was blood manganese. It is inferred that deposition of high concentrations of manganese may

Acknowledgements

The authors thank M. Ohara for language assistance.

References (17)

A Matsui et al.
Identification of infants with biliary atresia in Japan
Lancet
(1994)
R Ohi et al.
Long-term follow-up after surgery for patients with biliary atresia
J Pediatr Surg
(1990)
AG Devenyi et al.
Dystonia, hyperintense basal ganglia and high whole blood manganese level in Alagilles syndrome
Gastroenterology
(1994)
L Spahr et al.
Increased blood manganese in cirrhotic patients: Relationship to pallidal magnetic resonance signal hyperintensity and neurological symptoms
Hepatology
(1996)
SEM Ibim et al.
Depletion of essential elements by calcium disodium EDTA treatment in the dog
Toxicology
(1992)
M Nio et al.
Long-term outcome of surgery for biliary atresia
J Jpn Surg Soc
(1996)
T Kashiwagi et al.
Portosystemic shunting in portal hypertension: Evaluation with portal scintigraphy with transrectally administered I-123IMP
Radiology
(1988)
E Inoue et al.
Portal-systemic encephalopathy: Presence of basal ganglia lesions with high signal intensity on MR images
Radiology
(1991)

There are more references available in the full text version of this article.

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^☆: Address reprint requests to Shinji Ikeda, MD, Department of Pediatric Surgery, Kumamoto University Medical School, Honjo 1-1-1, Kumamoto 860-8544, Japan.

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Manganese deposits in patients with biliary atresia after hepatic porto-enterostomy☆

Abstract

Section snippets

Materials and methods

Results

Discussion

Acknowledgements

Lancet

J Pediatr Surg

Gastroenterology

Hepatology

Toxicology

Long-term outcome of surgery for biliary atresia

J Jpn Surg Soc

Portosystemic shunting in portal hypertension: Evaluation with portal scintigraphy with transrectally administered I-123IMP

Radiology

Portal-systemic encephalopathy: Presence of basal ganglia lesions with high signal intensity on MR images

Radiology