Successful heterozygous living donor liver transplantation for an oxysterol 7α-hydroxylase deficiency in a Japanese patient

Abstract

Only 2 patients with an oxysterol 7a-hydroxylase deficiency caused by mutations of the cytochrome P450 7B1 (CYP7B1) gene have been reported; for both, the outcome was fatal. We describe the clinical and laboratory features, the hepatic and renal histological findings, and the results of bile acid and CYP7B1 gene analyses for a third patient. This Japanese infant presented with progressive cholestatic liver disease and underwent successful heterozygous living donor liver transplantation. Sources of relevant data included medical records, hepatic and renal histopathological findings, gas chromatography/ mass spectrometry analyses of bile acids in serum and urine samples, and analyses of the CYP7B1 gene in the DNA of peripheral blood lymphocytes. Large excesses of 3b-hydroxy-5-cholen-24-oic acid were detected in the patient's serum and urine. Cirrhosis and polycystic changes in the kidneys were documented. The demonstration of compound heterozygous mutations (R112X/R417C) of the CYP7B1 gene led to the diagnosis of an oxysterol 7a-hydroxylase deficiency. After liver transplantation with an allograft from a heterozygous living donor (the patient's mother), the features of decompensated hepatocellular failure abated, and the renal abnormalities were resolved. In conclusion, we report the first Japanese patient with an oxysterol 7a-hydroxylase deficiency associated with compound heterozygous mutations of the CYP7B1 gene; in this patient, liver transplantation with an allograft from a parental donor was effective.

Cholestenoic acids regulate motor neuron survival via liver X receptors

“…circulation. We previously investigated the plasma oxysterol and cholestenoic acid profile of 3 infants with mutations in CYP7B1 (Supplemental Table 2) resulting in oxysterol 7α-hydroxylase deficiency (O7AHD) and neonatal liver disease (27)(28)(29)(30), as well as SPG5 in adults (31). The first identification of CYP7B1 mutations were found in a child with severe cholestasis (32), defining a new inborn error of bile acid biosynthesis.…”

A blood test for cerebrotendinous xanthomatosis with potential for disease detection in newborns

“…The mean plasma concentrations of 7 ␣ C4, 7 ␣ 12 ␣ C4, and 5 ␣ -cholestanol measured in CTX-affected adults were, respectively, 183-, 3862-, and 24-fold the mean concentrations in unaffected adults, with no The acidic BA pathway initiated by cholesterol 27-hydroxylation (lower pathway in Fig. 1 ) has been proposed to be the major BA synthesis pathway in neonates, as deficiency in the oxysterol 7 ␣ -hydroxylase enzyme (CYP7B1) can cause severe liver disease in infancy (36)(37)(38). Our data and the recent observation that CYP7B1 mutations also cause a form of hereditary spastic paraplegia with disease onset outside of the newborn period ( 39 ) suggest that when the acidic pathway is blocked, neonates are able to synthesize BA via the neutral pathway.…”

Tandem Mass Spectrometric Determination of Atypical 3β-Hydroxy-Δ5-Bile Acids in Patients with 3β-Hydroxy-Δ5-C27-Steroid Oxidoreductase Deficiency: Application to Diagnosis and Monitoring of Bile Acid Therapeutic Response

“…With collision-induced dissociation of the parent ion, all of the 3␤-hydroxy-⌬ 5 -bile acid sulfates yielded a common intense base peak at m/z 96.6 resulting from loss of the sulfate group. Consequently, the deprotonated molecular ion and its [HSO 4 Ϫ ] fragment were selected as the appropriate mass transition pairs for monitoring and quantifying all the 3␤-hydroxy-⌬ 5 -bile acid sulfates by LC-ESI-MS/MS (Fig. 1A).…”