Death after Transplantation of a Liver from a Donor with Unrecognized Ornithine Transcarbamylase Deficiency

Plöchl, Walter; Spiss, Christian K.; Plöchl, E

doi:10.1056/nejm199909163411214

Cited by 29 publications

(24 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Male hemizygotes of OTCD can range in severity from fatal neonatal hyperammonaemic coma to asymptomatic adults. Indeed, it was reported that the recipient of a liver harvested from an adult male deceased donor who had unrecognized OTCD died as a result of hyperammonemia (32). Therefore, a genetic assay is necessary to exclude male hemizygotes from blood relative donor candidates for females with OTCD, and if male hemizygotes for OTCD are identified, they must be strictly followed-up, because such individuals may themselves be candidates for LT due to their risk of developing sudden hyperammonaemic coma.…”

Section: Discussionmentioning

confidence: 99%

Living Donor Liver Transplantation for Pediatric Patients with Inheritable Metabolic Disorders

Morioka

Kasahara

Takada

et al. 2005

American Journal of Transplantation

104

111

View full text Add to dashboard Cite

Forty-six pediatric patients who underwent living donor liver transplantation (LDLT) using parental liver grafts for inheritable metabolic disorders (IMD) were evaluated to determine the outcomes of the surgery, decisive factors for post-transplant patient survival and the impact of using donors who were heterozygous for the particular disorder. Disorders included Wilson disease (WD, n = 21), ornithine transcarbamylase deficiency (OTCD, n = 6), tyrosinemia type I (TTI, n = 6), glycogen storage disease (GSD, n = 4), propionic acidemia (PPA, n = 3), methylmalonic acidemia (MMA, n = 2), Crigler-Najjar syndrome type I (CNSI, n = 2), bile acid synthetic defect (BASD, n = 1) and erythropoietic protoporphyria (EPP, n = 1). The post-transplant cumulative patient survival rates were 86.8 and 81.2% at 1 and 5 years, respectively. Posttransplant patient survival and recovery of the growth retardation were significantly better in the liveroriented diseases (WD, OTCD, TTI, CNSI and BASD) than in the non-liver-oriented diseases (GSD, PPA, MMA and EPP) and pre-transplant growth retardation disadvantageously affected post-transplant outcomes. Although 40 of 46 donors were considered heterozygous for each disorder, neither mortality nor morbidity related to the heterozygosis has been observed. LDLT using parental donors can be recommended as an effective treatment for pediatric patients with IMD. In the non-liver-oriented diseases, however, satisfactory outcomes were not obtained by hepatic replacement alone.

show abstract

Section: Discussionmentioning

confidence: 99%

Living Donor Liver Transplantation for Pediatric Patients with Inheritable Metabolic Disorders

Morioka

Kasahara

Takada

et al. 2005

American Journal of Transplantation

104

111

View full text Add to dashboard Cite

show abstract

“…Although the Australian family has no known Spanish ancestry, the proband's maternal grandfather (not studied) was of North Italian descent and could conceivably share ancestry with the Spanish family. It remains possible that the mutation occurred recurrently, but it is noteworthy that the allele in these families has a low haplotype frequency (0.033) among 25 Present report Present report Arranz et al 27 Pinner et al 28 Plöchl et al 23 Tuchman et al, 11 Tuchman et al 10 Kim et al 29 McCullough et al 14 Nishiyori et al 16 Caucasians. Families 12 and 13 share a haplotype, but there is insufficient information to say whether this represents the effect of common ancestry or of recurrence on the same haplotype.…”

Section: Discussionmentioning

confidence: 78%

“…In family 12, the DNA specimen of the proband was prepared from the liver tissue obtained after it had been inadvertently transplanted to a woman. 23 …”

Section: Materials and Methods Familiesmentioning

confidence: 99%

Mutant alleles associated with late-onset ornithine transcarbamylase deficiency in male patients have recurrently arisen and have been retained in some populations

et al. 2009

View full text Add to dashboard Cite

We performed haplotype analysis using nine single nucleotide polymorphisms in the ornithine transcarbamylase gene to explore the ancestral origins of three mutations associated with late-onset phenotype in male patients: p.R40H, p.R277W and p.Y55D. Overall, 8 haplotypes were defined among 14 families carrying p.R40H, 5 families carrying p.R277W and 2 families with p.Y55D mutations. Of nine Japanese families carrying p.R40H, eight exhibited haplotype (HT)1, whereas the other family harbored HT2. Among three Caucasian families, one Spanish and one Australian family bore HT3; one Austrian family had HT4. Two US patients harbored HT2 and HT4. Among families carrying p.R277W, HT5 was found in one Japanese, one Korean and one US family. Two other US families had HT2 and HT6. Two families carrying p.Y55D, both Japanese, shared HT1. These results indicate that the p.R40H mutation has arisen recurrently in all populations studied, although there is evidence for a founder effect in Japan, with most cases probably sharing a common origin, and to a lesser extent in subjects of European ancestry (HT3). It is evident that p.R277W mutation has recurred in discrete populations. The p.Y55D mutation appears to have arisen from a common ancestor, because this transversion (c.163T4G) occurs rarely.

show abstract

“…In contrast, certain mutations were repeatedly found in families in the series reported here that are reportedly unrelated, although all the R40H mutant alleles in the series were found in families living in an area with a radius of 120 km, suggesting a possible common ancestral origin. In addition, this mutant allele has occurred recurrently (Tuchman et al 1995;Plöchl et al 1999;Arranz et al 2007;Pinner et al personal communication). Thus, R40H alleles may be maintained mostly by transmission from ancestors to their offspring, with occasional addition by de novo mutation.…”

Section: Discussionmentioning

confidence: 98%

“…However, the R40H mutation has been found in discrete families in the Japanese population (Matsuda et al 1996;Nishiyori et al 1997;Harada et al 2006) and in other ethnic groups (Tuchman et al 1995;Plöchl et al 1999;Arranz et al 2007). The R277W mutation was also found in multiple families with different ethnic origins (Finkelstein et al 1990b;Hata et al 1991;Matsuura et al 1993; present series).…”

Section: Introductionmentioning

confidence: 99%

Paternal transmission and slow elimination of mutant alleles associated with late-onset ornithine transcarbamylase deficiency in male patients

et al. 2007

View full text Add to dashboard Cite

In ten families with late-onset ornithine transcarbamylase (OTC) deficiency in male patients, three mutant alleles-R40H, R277W, and Y55D-were identified. In a total of 20 informative parent-offspring pairs, father-to-daughter transmission and mother-to-offspring transmission occurred in five (25%) and 15 (75%), respectively, indicating that paternal transmission contributes substantially to the pool of these mutant alleles. Relative reproductive fitness of males and females carrying the mutant alleles was calculated to be 0.49 and 0.89, respectively. Comparison of the life span of the mutant alleles, estimated on the basis of these fitness values with those associated with classic phenotype (neonatal onset) in which reproductive fitness of male patients was nil, revealed that mutant alleles associated with the late-onset phenotype were eliminated more slowly. This would allow the late-onset phenotype mutant alleles to be retained more frequently in a population than those associated with classic phenotype. Although heterozygous females carrying the late-onset phenotype mutant alleles were generally asymptomatic, one female carrying the R40H allele died after a hyperammonemic episode at the age of 18 years. Such heterozygous females should be alerted to possible hyperammonemic crisis.

show abstract

Death after Transplantation of a Liver from a Donor with Unrecognized Ornithine Transcarbamylase Deficiency

Cited by 29 publications

References 4 publications

Living Donor Liver Transplantation for Pediatric Patients with Inheritable Metabolic Disorders

Living Donor Liver Transplantation for Pediatric Patients with Inheritable Metabolic Disorders

Mutant alleles associated with late-onset ornithine transcarbamylase deficiency in male patients have recurrently arisen and have been retained in some populations

Paternal transmission and slow elimination of mutant alleles associated with late-onset ornithine transcarbamylase deficiency in male patients

Contact Info

Product

Resources

About