title: Living-Donor Liver Transplantation From a Heterozygous Parent for Infantile Refsum Disease.
abstract: Infantile Refsum disease (IRD) is a rare autosomal recessive disorder of peroxisome biogenesis characterized by generalized peroxisomal metabolic dysfunction, including accumulation of very long-chain fatty acids (VLCFAs) and phytanic acid (PA), as well as decreased plasmalogen contents (PL). An effective therapy for this intractable disease has not been established, and only supportive management with docosahexaenoic acid supplementation and low PA diet has been reported so far. A boy of 3 years and 8 months presented with facial dysmorphism, transaminitis, and psychomotor retardation. Biochemical analysis showed elevated PA and VLCFAs, with reduced PL in the serum. Immunofluorescence study of fibroblasts from the patient indicated a mosaic pattern of catalase-positive and -negative particles, and molecular analysis revealed compound heterozygous mutations of PEX6 The failure of medical management to prevent the progression of clinical symptoms and abnormal biochemistry prompted us to consider liver transplantation (LT). With the chances of receiving a deceased donor liver being poor, we performed a living-donor LT from the patient's heterozygous mother. At 6-month follow-up, the patient's serum PA levels had normalized. VLCFAs and PL levels had declined and increased, respectively. To the best of our knowledge, this is the second reported case in which IRD was treated by living-donor LT by using a heterozygous donor. Only long-term follow-up will reveal if there is any clinical improvement in the present case. With the liver being a major site for peroxisomal pathways, its replacement by LT may work as a form of partial enzyme therapy for patients with IRD.
authors.affiliation: Organ Transplantation Center, and matsunami-m@ncchd.go.jp.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Matsunami
authors.affiliation: Division of Genomics Research, Life Science Research Center, Gifu University, Gifu, Japan; and.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Shimozawa
authors.affiliation: Organ Transplantation Center, and.
authors.forename: Akinari
authors.initials: A
authors.lastname: Fukuda
authors.affiliation: Division of Neurology, National Center for Child Health and Development, Tokyo, Japan;
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Kumagai
authors.affiliation: Division of Neurology, National Center for Child Health and Development, Tokyo, Japan;
authors.forename: Masaya
authors.initials: M
authors.lastname: Kubota
authors.affiliation: Department of Pediatric Neurology, Fukuoka Children's Hospital, Fukuoka, Japan.
authors.forename: Pin Fee
authors.initials: PF
authors.lastname: Chong
authors.affiliation: Organ Transplantation Center, and.
authors.forename: Mureo
authors.initials: M
authors.lastname: Kasahara
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics; D002675:Child, Preschool; D005227:Fatty Acids / Q000097:blood; D005260:Female; D006579:Heterozygote; D006801:Humans; D016031:Liver Transplantation; D019520:Living Donors; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D010831:Phytanic Acid / Q000097:blood; D052919:Refsum Disease, Infantile / Q000235:genetics / Q000601:surgery*; D066127:White Matter / Q000000981:diagnostic imaging / Q000473:pathology
chemical_list: D005227:Fatty Acids; D010831:Phytanic Acid; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities; C490759:PEX6 protein, human