Letter to the Editorped_3624 443

3b-Hydroxy-D5-C27-steroid dehydrogenase/isomerase deficiency in apatient who underwent oral bile acid therapy for 10 years anddelivered two healthy infants: Reply

Hiroshi Nittono

Junshin Clinic Bile Acid Institute, Tokyo, Japan

The article by Gonzales et al.1 had not been reported as of March2009, when we submitted our article. Our report was accepted inJanuary 2011, and we were not aware of the report by Gonzaleset al. during this period.

Although our report describes the concomitant use of cheno-deoxycholic acid (CDCA) and cholic acid (CA), and differs fromthe single use of CA by Gonzales et al., we concede that Gonza-les et al. reported on the fact that “A patient who underwentprimary bile acid therapy for IEBAM (inborn error of bile acidmetabolism) gave birth to a normal baby” ahead of us. For thisreason, we will revise our report from being the first case in theworld to the first case in Japan.

The reason for concomitantly using CDCA and CA for3b-hydroxy-D5-C27-steroid dehydrogenase/isomerase (3b-HSD)deficiency is based on the fact that abnormal bile acid in the urinedecreased the most due to CDCA + CA from among the testedoptions of ursodeoxycholic acid, CDCA, CA, and CDCA + CA.2

CA was originally not sold in Japan as a drug formulation, and sowe referred to reports by Ichimiya et al. and the use of CDCA incerebrotendinous xanthomatosis as the fundamental therapy forbile acid,3,4 and CA was given only at a low dose. The purpose ofCDCA + CA was to reduce the production of abnormal bile acidas much as possible, rather than to target the bile acid composi-tion of healthy individuals.

We ourselves confirmed that the hepatotoxicity of CDCA isvery strong.5 Therefore, we are following up this patient by

periodically testing the liver function and total bile acid in theserum as well as identifying any abnormal bile acid in the urineto confirm that there are no abnormalities. There were no abnor-malities observed during the neonatal period in the bile acid inthe urine of the babies born to this patient.

Cholic acid could not be obtained in Japan and in this case,we switched to the single use of CDCA from January 2009. Forthe time being, however, normal liver function has been main-tained. Against this background, we plan to continue to useCDCA for patients in Japan with 3b-HSD deficiency. Needlessto say, we believe that careful testing of liver function andregular analysis for any abnormal bile acid in the urine arenecessary.

Please accept our sincere apologies for any inconveniencecaused to the persons involved regarding this issue.

References

1 Gonzales E, Gerhardt MF, Fabre M et al. Oral cholic acid for heredi-tary defects of primary bile acid synthesis: A safe and effectivelong-term therapy. Gastroenterology 2009; 137: 1310–20.

2 Kobayashi M, Koike M, Sakiyama M et al. 3b-Hydroxy-D5-C27-steroid dehydrogenase/isomerase deficiency in a 23-year oldwoman. Pediatr. Int. 2000; 42: 685–8.

3 Ichimiya H, Nazer H, Gunasekaran T, Clayton P, Sjövall J. Treat-ment of chronic liver disease caused by 3b-hydroxy-D5-C27-sterioddehydrogenase deficiency with chenodeoxycholic acid. Arch. Dis.Child. 1990; 65: 1121–4.

4 Batta AK, Shefer S, Batta M, Salen G. Effect of chenodeoxycholicacid on biliary and urinary bile acids and bile alcohols in cerebro-tendinous xanthomatosis; monitoring by high performance liquidchromatography. J. Lipid Res. 1985; 26: 690–98.

5 Nittono H. Studies on the toxicity of bile acid in infants. Part1.Effect of orally fed bile acids on the hepatobiliary system in rabbits.Acta Paediatr. Jpn 1979; 21: 11–24.

Correspondence: Hiroshi Nittono, MD PhD, Junshin Clinic Bile AcidInstitute, 2-1-22, Hara-machi, Meguro-ku, Tokyo 152-0011, Japan.Email: bile-res@eco.ocn.ne.jp

Received 10 June 2011; revised 1 December 2011; accepted 6 March2012.

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Pediatrics International (2012) 54, 443 doi: 10.1111/j.1442-200X.2012.03624.x

© 2012 The AuthorPediatrics International © 2012 Japan Pediatric Society