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Living-Donor Liver Transplantation From a Heterozygous Parent for Infantile Refsum Disease
Masatoshi Matsunami1, Nobuyuki Shimozawa2, Akinari Fukuda3
1Organ Transplantation Center, and matsunami-m@ncchd.go.jp.
Insights
Infantile Refsum disease (IRD) is a rare metabolic disorder. Liver transplantation using a heterozygous donor normalized phytanic acid levels and improved other biomarkers in a young patient.
Area of Science:
- Biochemistry
- Genetics
- Pediatrics
Background:
- Infantile Refsum disease (IRD) is a rare, inherited peroxisomal disorder.
- Characterized by metabolic dysfunction, including elevated very long-chain fatty acids (VLCFAs) and phytanic acid (PA), and low plasmalogens (PL).
- Current treatments are supportive, lacking established therapies for this intractable condition.
Observation:
- A 3-year-old boy presented with dysmorphism, liver dysfunction, and psychomotor delay.
- Biochemical tests revealed high PA and VLCFAs, with low PL.
- Fibroblast analysis showed mosaic peroxisomal defects, with PEX6 mutations identified.
Findings:
- Liver transplantation (LT) was performed using a heterozygous living donor due to the severity and lack of response to medical management.
- Post-transplant, serum PA normalized, VLCFAs decreased, and PL levels increased at 6 months.
- This is the second reported case of IRD treated with living-donor LT from a heterozygous donor.
Implications:
- Liver transplantation may serve as a partial enzyme replacement therapy for IRD, given the liver's role in peroxisomal pathways.
- Long-term follow-up is necessary to assess clinical improvement.
- This case highlights living-donor LT as a viable option for IRD when deceased donors are unavailable.
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.
