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1.
J Inherit Metab Dis ; 47(2): 220-229, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38375550

RESUMO

Carbamoyl phosphate synthetase 1 (CPS1) and ornithine transcarbamylase (OTC) deficiencies are rare urea cycle disorders, which can lead to life-threatening hyperammonemia. Liver transplantation (LT) provides a cure and offers an alternative to medical treatment and life-long dietary restrictions with permanent impending risk of hyperammonemia. Nevertheless, in most patients, metabolic aberrations persist after LT, especially low plasma citrulline levels, with questionable clinical impact. So far, little is known about these alterations and there is no consensus, whether l-citrulline substitution after LT improves patients' symptoms and outcomes. In this multicentre, retrospective, observational study of 24 patients who underwent LT for CPS1 (n = 11) or OTC (n = 13) deficiency, 25% did not receive l-citrulline or arginine substitution. Correlation analysis revealed no correlation between substitution dosage and citrulline levels (CPS1, p = 0.8 and OTC, p = 1). Arginine levels after liver transplantation were normal after LT independent of citrulline substitution. Native liver survival had no impact on mental impairment (p = 0.67). Regression analysis showed no correlation between l-citrulline substitution and failure to thrive (p = 0.611) or neurological outcome (p = 0.701). Peak ammonia had a significant effect on mental impairment (p = 0.017). Peak plasma ammonia levels correlate with mental impairment after LT in CPS1 and OTC deficiency. Growth and intellectual impairment after LT are not significantly associated with l-citrulline substitution.


Assuntos
Hiperamonemia , Transplante de Fígado , Doença da Deficiência de Ornitina Carbomoiltransferase , Humanos , Doença da Deficiência de Ornitina Carbomoiltransferase/cirurgia , Hiperamonemia/tratamento farmacológico , Citrulina , Carbamoil-Fosfato/metabolismo , Carbamoil-Fosfato/uso terapêutico , Amônia/metabolismo , Estudos Retrospectivos , Carbamoil-Fosfato Sintase (Amônia)/metabolismo , Arginina/uso terapêutico , Ornitina Carbamoiltransferase
2.
Paediatr Anaesth ; 33(8): 620-630, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37401903

RESUMO

BACKGROUND: Ornithine transcarbamylase deficiency is an X-linked genetic disorder that induces accumulation of ammonia in the liver and is the most common urea cycle disorder. The clinical manifestation of ornithine transcarbamylase deficiency is hyperammonemia that causes irreversible neurological damage. Liver transplantation is a curative therapy for ornithine transcarbamylase deficiency. The aim of this study is to suggest, from our previous experience, an anesthesia management protocol of liver transplantation for ornithine transcarbamylase deficiency, particularly focused on liver transplantation for cases with uncontrolled hyperammonemia. METHOD: We retrospectively reviewed our anesthesia-related experience in all cases of liver transplantation for ornithine transcarbamylase deficiency in our center. RESULTS: Twenty-nine liver transplantation cases for ornithine transcarbamylase deficiency were found between November 2005 and March 2021 in our center. Of these, 25 cases were stable through the perioperative period. However, 2 cases with carrier donor graft had hyperammonemia after liver transplantation. Another two cases had uncontrolled hyperammonemia before liver transplantation, even with continuous hemodialysis. They underwent life-saving liver transplantation. Their metabolic status stabilized after the anhepatic phase. CONCLUSION: Liver transplantation for cases with uncontrolled hyperammonemia can be performed with proper management. Second, liver transplantation with carrier donors should be avoided because of the risk of postoperative recurrence.


Assuntos
Anestesia , Hiperamonemia , Transplante de Fígado , Doença da Deficiência de Ornitina Carbomoiltransferase , Humanos , Doença da Deficiência de Ornitina Carbomoiltransferase/cirurgia , Doença da Deficiência de Ornitina Carbomoiltransferase/tratamento farmacológico , Doença da Deficiência de Ornitina Carbomoiltransferase/genética , Hiperamonemia/cirurgia , Hiperamonemia/etiologia , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Anestesia/efeitos adversos
3.
Brain Behav ; 12(10): e2765, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36128655

RESUMO

BACKGROUND: Ornithine transcarbamylase deficiency (OTCD) is a genetic metabolic disease. Its clinical manifestations are mainly central nervous system dysfunction caused by high blood ammonia. Late-onset OTCD combined with central nervous system injury has a poor therapeutic response, which is one of the main factors affecting the prognosis and quality of life of patients. liver transplantation (LT) has gradually become a radical treatment for OTCD, which has achieved good results. However, there is no consensus on the timing of LT and problems of nervous system damage and repair. METHODS: We report the development of late-onset OTCD with central nervous system injury in an 11-year-old child who received liver transplantation at our transplant center. His first symptoms were nonprojectile vomiting, followed by irritability and disturbance of consciousness, after which the disease progressed rapidly and finally resulted in a coma. After liver transplantation, the child's consciousness returned to normal, muscle strength of the limbs gradually recovered from grade 0 to grade 4, and muscle tone gradually recovered from grade 4 to grade 1, suggesting that the motor nerves had gradually recovered. However, the child is currently mentally retarded, and the language center has not yet fully recovered.At the same time, we made a literature review of OTCD. CONCLUSION: For OTCD patients with central nervous system injury, liver transplantation can fundamentally solve the problem of ammonia metabolism in the liver and avoids further damage to the central nervous system caused by hyperammonemia. At the same time, children's nervous systems are in the developmental stage when neuroplasticity is greatest. If liver transplantation is performed as soon as possible, nerve repair is still possible.


Assuntos
Transplante de Fígado , Doença da Deficiência de Ornitina Carbomoiltransferase , Amônia/uso terapêutico , Sistema Nervoso Central , Criança , Humanos , Doença da Deficiência de Ornitina Carbomoiltransferase/complicações , Doença da Deficiência de Ornitina Carbomoiltransferase/cirurgia , Qualidade de Vida
4.
Am J Med Genet A ; 185(3): 909-915, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33369132

RESUMO

We describe 10 females with ornithine transcarbamylase (OTC) deficiency and liver dysfunction, revealing a unique pattern of hepatocyte injury in which initial hyperammonemia and coagulopathy is followed by a delayed peak in aminotransferase levels. None of the patients required urgent liver transplantation, though five eventually underwent transplant for recurrent metabolic crises. We intend that this novel observation will initiate further investigations into the pathophysiology of liver dysfunction in OTC-deficient patients, and ultimately lead to the development of therapies and prevent the need for liver transplant.


Assuntos
Alanina Transaminase/sangue , Hepatopatias/etiologia , Doença da Deficiência de Ornitina Carbomoiltransferase/complicações , Idade de Início , Substituição de Aminoácidos , Aspartato Aminotransferases/sangue , Biomarcadores , Pré-Escolar , Terapia Combinada , Deficiências do Desenvolvimento/genética , Progressão da Doença , Feminino , Transtornos Hemorrágicos/etiologia , Humanos , Hiperamonemia/genética , Lactente , Coeficiente Internacional Normatizado , Hepatopatias/sangue , Hepatopatias/cirurgia , Transplante de Fígado , Mutação de Sentido Incorreto , Doença da Deficiência de Ornitina Carbomoiltransferase/sangue , Doença da Deficiência de Ornitina Carbomoiltransferase/dietoterapia , Doença da Deficiência de Ornitina Carbomoiltransferase/cirurgia , Vômito/genética
6.
Exp Clin Transplant ; 17(1): 119-120, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-27447480

RESUMO

One of the X chromosome-linked disorders is ornithine transcarbamylase deficiency in the urea cycle. This disorder results in increased ammonia and glutamine in the blood. Accumulation of these metabolites without treatment causes brain edema, which often progresses to coma and death. This study describes a 5-year-old girl with ornithine transcarbamylase deficiency who presented with hyperammonemic encephalopathy that was successfully treated with an orthotropic liver transplant. Recently, liver transplant has been introduced as an alternative treatment for patients with ornithine transcarbamylase deficiency.


Assuntos
Encefalopatia Hepática/cirurgia , Hiperamonemia/cirurgia , Transplante de Fígado , Doença da Deficiência de Ornitina Carbomoiltransferase/cirurgia , Pré-Escolar , Feminino , Encefalopatia Hepática/sangue , Encefalopatia Hepática/diagnóstico , Encefalopatia Hepática/etiologia , Humanos , Hiperamonemia/sangue , Hiperamonemia/diagnóstico , Hiperamonemia/etiologia , Doença da Deficiência de Ornitina Carbomoiltransferase/sangue , Doença da Deficiência de Ornitina Carbomoiltransferase/complicações , Doença da Deficiência de Ornitina Carbomoiltransferase/diagnóstico , Resultado do Tratamento
7.
Medicine (Baltimore) ; 97(51): e13843, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30572553

RESUMO

RATIONALE: Graft-derived-cell-free DNA (Gcf-DNA) in plasma was a promising biomarker to monitor graft-rejection after liver transplantation. However, little is known about the application of Gcf-DNA in living-donor-liver-transplantation (LDLT). PATIENTS CONCERN: In this study, 2 patients diagnosed with Ornithine Transcarbamylase Deficiency (OTCD) were enrolled and indicated for LDLT. DIAGNOSES: Two patients were genetically diagnosed with OTCD, and they suffered from recurrent and uncontrollable hyper-ammonemia and failed in accepting the normalized OTCD treatments, such as decreasing dietary nitrogen intake and increasing waste-nitrogen excretion. INTERVENTIONS: LDLT was performed in the 2 patients uneventfully, and we collected circulating cell-free DNA from plasma in specific postoperative time points (day 1, day 7, day 14, day 30, day 60). Since both of the recipients were sex-mismatch with the donors, we measured Gcf-DNA through the Y-chromosome method and compared it with the routine liver function. OUTCOMES: The result showed that Gcf-DNA had the similar discrimination of graft injury trend while compared to routine liver function. The follow-up showed these 2 patients' status is stable. LESSONS: Applying Gcf-DNA to monitor graft injury in LDLT is promising, but still long term follow-up and more samples are needed for validation.


Assuntos
Ácidos Nucleicos Livres/sangue , Rejeição de Enxerto/sangue , Transplante de Fígado , Doença da Deficiência de Ornitina Carbomoiltransferase/sangue , Doença da Deficiência de Ornitina Carbomoiltransferase/cirurgia , Biomarcadores/sangue , Feminino , Humanos , Lactente , Testes de Função Hepática , Doadores Vivos , Masculino , Doença da Deficiência de Ornitina Carbomoiltransferase/genética , Resultado do Tratamento
8.
World J Gastroenterol ; 23(46): 8227-8234, 2017 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-29290659

RESUMO

AIM: To assess the efficacy and safety of balloon dilatation for the treatment of hepatic venous outflow obstruction (HVOO) following pediatric liver transplantation. METHODS: A total of 246 pediatric patients underwent liver transplantation at our hospital between June 2013 and September 2016. Among these patients, five were ultimately diagnosed with HVOO. Seven procedures (two patients underwent two balloon dilatation procedures) were included in this analysis. The demographic data, types of donor and liver transplant, interventional examination and therapeutic outcomes of these five children were analyzed. The median interval time between pediatric liver transplantation and balloon dilatation procedures was 9.8 mo (range: 1-32). RESULTS: Five children with HVOO were successfully treated by balloon angioplasty without stent placement, with seven procedures performed for six stenotic lesions. All children underwent successful percutaneous intervention. Among these five patients, four were treated by single balloon angioplasty, and these patients did not develop recurrent stenosis. In seven episodes of balloon angioplasty across the stenosis, the pressure gradient was 12.0 ± 8.8 mmHg before balloon dilatation and 1.1 ± 1.5 mmHg after the procedures, which revealed a statistically significant reduction (P < 0.05). The overall technical success rate among these seven procedures was 100% (7/7), and clinical success was achieved in all five patients (100%). The patients were followed for 4-33 mo (median: 15 mo). No significant procedural complications or procedure-related deaths occurred. CONCLUSION: Balloon dilatation is an effective and safe therapeutic option for HVOO in children undergoing pediatric liver transplantation. Venous angioplasty is also recommended in cases with recurrent HVOO.


Assuntos
Angioplastia com Balão/métodos , Síndrome de Budd-Chiari/terapia , Dilatação/métodos , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/terapia , Angioplastia com Balão/efeitos adversos , Atresia Biliar/cirurgia , Síndrome de Budd-Chiari/epidemiologia , Síndrome de Budd-Chiari/etiologia , Criança , Pré-Escolar , Constrição Patológica/epidemiologia , Constrição Patológica/etiologia , Constrição Patológica/terapia , Dilatação/efeitos adversos , Feminino , Seguimentos , Veias Hepáticas/patologia , Humanos , Incidência , Lactente , Masculino , Doença da Deficiência de Ornitina Carbomoiltransferase/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do Tratamento
9.
Orphanet J Rare Dis ; 11(1): 116, 2016 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-27538463

RESUMO

BACKGROUND: Urea cycle disorders (UCDs) are rare inherited metabolic defects of ammonia detoxification. In about half of patients presenting with a UCD, the first symptoms appear within a few days after birth. These neonatal onset patients generally have a severe defect of urea cycle function and their survival and outcome prognoses are often limited. To understand better the current situation of neonatal onset in UCDs, we have performed a multicentre, retrospective, non-interventional case series study focussing on the most severe UCDs, namely defects of carbamoyl phosphate synthetase 1 (CPS1), ornithine transcarbamylase (OTC), and argininosuccinate synthetase (ASS). METHODS AND RESULTS: Data of 63 patients were collected (27 patients with ASS deficiency, 23 patients with OTC deficiency, and 12 patients with CPS1 deficiency, one patient definite diagnosis not documented). The majority of patients (43/63, 68 %) had an initial ammonia concentration exceeding 500 µmol/L (normal < 100), of which most (26/43, 60.5 %) were also encephalopathic and were treated with hemodialysis. In patients surviving the initial crisis, recurrence of hyperammonemic events within the first 1.5 years of life occurred frequently (mean 3.6 events, range 0-20). Of all patients, 16 (25.4 %) died during or immediately after the neonatal period. CONCLUSION: We observed in this cohort of neonatal onset UCD patients a high rate of initial life-threatening hyperammonemia and a high risk of recurrence of severe hyperammonemic crises. These corresponded to a high mortality rate during the entire study period (30.2 %) despite the fact that patients were treated in leading European metabolic centers. This underlines the need to critically re-evaluate the current treatment strategies in these patients.


Assuntos
Hiperamonemia/patologia , Distúrbios Congênitos do Ciclo da Ureia/patologia , Arginina/uso terapêutico , Pré-Escolar , Feminino , Humanos , Hiperamonemia/tratamento farmacológico , Hiperamonemia/mortalidade , Hiperamonemia/cirurgia , Lactente , Estimativa de Kaplan-Meier , Transplante de Fígado , Masculino , Doença da Deficiência de Ornitina Carbomoiltransferase/tratamento farmacológico , Doença da Deficiência de Ornitina Carbomoiltransferase/mortalidade , Doença da Deficiência de Ornitina Carbomoiltransferase/patologia , Doença da Deficiência de Ornitina Carbomoiltransferase/cirurgia , Prognóstico , Estudos Retrospectivos , Benzoato de Sódio/uso terapêutico , Distúrbios Congênitos do Ciclo da Ureia/tratamento farmacológico , Distúrbios Congênitos do Ciclo da Ureia/mortalidade , Distúrbios Congênitos do Ciclo da Ureia/cirurgia
10.
Exp Clin Transplant ; 13 Suppl 3: 126-30, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26640932

RESUMO

Urea cycle defects are a group of metabolic disorders caused by enzymatic disruption of the urea cycle pathway, transforming nitrogen to urea for excretion from the body. Severe cases present in early infancy with life-threatening metabolic decompensation, and these episodes of hyperammonemia can be fatal or result in permanent neurologic damage. Despite the progress in pharmacologic treatment, long-term survival is poor especially for severe cases. Liver transplant is an alternative treatment option, providing sufficient enzymatic activity and decreasing the risk of metabolic decompensation. Three patients with urea cycle defects received related living-donor liver transplants at our hospital. Patients presented with late-onset ornithine transcarbamylase deficiency, argininosuccinate lyase deficiency, and citrullinemia. Maximum pretransplant ammonia levels were between 232 and 400 µmol/L (normal range is 18-72 µmol/L), and maximum posttransplant values were 52 to 94 µmol/L. All patients stopped medical treatment and dietary protein restriction for urea cycle defects after transplant. The patient with late-onset ornithine transcarbamylase deficiency already had motor deficits related to recurrent hyperammonemia attacks pretransplant. A major improvement could not be achieved, and he is wheelchair dependent at the age of 6 years. The other 2 patients had normal motor and mental skills before transplant, which have continued 12 and 14 months after transplant. Hepatic artery thrombosis in the patient with the ornithine transcarbamylase deficiency, intraabdominal infection in the patient with argininosuccinate lyase deficiency, and posterior reversible encephalopathy syndrome in the patient with citrullinemia were early postoperative complications. Histopathologic changes in livers explanted from patients with ornithine transcarbamylase deficiency and citrullinemia were nonspecific. The argininosuccinate lyase-deficient patient had portoportal fibrosis and cirrhotic nodule formation. In conclusion, liver transplant was a lifesaving procedure for our patients. Proper timing for transplant is important because high ammonia levels may result in permanent neurologic damage; however, transplant at younger ages also may increase morbidity.


Assuntos
Acidúria Argininossuccínica/cirurgia , Citrulinemia/cirurgia , Transplante de Fígado/métodos , Doadores Vivos , Doença da Deficiência de Ornitina Carbomoiltransferase/cirurgia , Acidúria Argininossuccínica/diagnóstico , Acidúria Argininossuccínica/genética , Criança , Citrulinemia/diagnóstico , Citrulinemia/genética , Pai , Feminino , Humanos , Lactente , Masculino , Mães , Doença da Deficiência de Ornitina Carbomoiltransferase/diagnóstico , Doença da Deficiência de Ornitina Carbomoiltransferase/genética , Resultado do Tratamento
12.
Mol Genet Metab ; 105(3): 404-7, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22264779

RESUMO

There are no objective and concrete guidelines for the management of Ornithine transcarbamylase deficiency (OTCD). Based on previous findings, we hypothesized that patients with OTCD have a low Ornithine transcarbamylase (OTC) activity in the liver, and therefore it would be better to determine the appropriate indications and optimal timing for liver transplantation (LT) based on the OTC activity. However, few data have so far been accumulated on the OTC activity in cases that are indicated for LT. The purpose of the present study was to clarify the OTC activity in cases that were indicated for LT. This study involved thirteen children with OTCD (8 males and 5 females) who underwent LT, and two females with OTCD who did not require LT. The OTC activity of the neonatal onset type ranged from 0% to 7.2%, while that of the late onset type who underwent LT ranged from 4.4% to 18.7%. The OTC activity of the late onset type which did not require LT was 33-38% based on a preoperative needle liver biopsy. Some late onset patients that underwent LT, showed an activity that was as low as that observed in the neonatal onset cases. This is the first report to show the results of measuring the OTC activity for serial OTCD cases indicated for LT. OTC activity might be an indicator to determine the indications for and the timing of LT in the late onset type, however, further investigations are necessary.


Assuntos
Ensaios Enzimáticos , Transplante de Fígado , Fígado/enzimologia , Doença da Deficiência de Ornitina Carbomoiltransferase/enzimologia , Doença da Deficiência de Ornitina Carbomoiltransferase/cirurgia , Ornitina Carbamoiltransferase/metabolismo , Adulto , Pré-Escolar , Feminino , Humanos , Hiperamonemia/complicações , Lactente , Recém-Nascido , Fígado/metabolismo , Masculino
13.
Pediatr Emerg Care ; 27(9): 850-3, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21926883

RESUMO

Recurrent abdominal pain remains one of the most common symptoms in pediatrics. We present the case of a 3-year-old girl who had recurrent episodes of abdominal pain requiring more than 13 visits to the emergency department. A diagnosis of ornithine transcarbamylase deficiency was eventually made. Urea cycle disorders often present beyond the neonatal period with frequent vomiting episodes; however, recurrent abdominal pain as a presenting symptom is unusual. Unnecessary invasive investigations of recurrent abdominal pain in childhood can be avoided by considering inborn errors of metabolism earlier in the differential diagnosis.


Assuntos
Dor Abdominal/etiologia , Doença da Deficiência de Ornitina Carbomoiltransferase/diagnóstico , Alcalose Respiratória/etiologia , Arginina/sangue , Doença da Deficiência da Carbamoil-Fosfato Sintase I/diagnóstico , Pré-Escolar , Citrulina/sangue , Citrulina/uso terapêutico , Transtornos da Consciência/etiologia , Diagnóstico Diferencial , Dieta com Restrição de Proteínas , Emergências , Éxons/genética , Feminino , Glutamina/sangue , Humanos , Hiperamonemia/etiologia , Transtornos do Desenvolvimento da Linguagem/etiologia , Transplante de Fígado , Mutação de Sentido Incorreto , Ornitina Carbamoiltransferase/genética , Doença da Deficiência de Ornitina Carbomoiltransferase/sangue , Doença da Deficiência de Ornitina Carbomoiltransferase/complicações , Doença da Deficiência de Ornitina Carbomoiltransferase/dietoterapia , Doença da Deficiência de Ornitina Carbomoiltransferase/tratamento farmacológico , Doença da Deficiência de Ornitina Carbomoiltransferase/cirurgia , Fenilbutiratos/uso terapêutico , Recidiva
14.
Transplantation ; 87(5): 636-41, 2009 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-19295306

RESUMO

BACKGROUND: Urea cycle disorders (UCD) have a poor prognosis despite dietary and pharmacologic therapy, especially if the onset of the disease is within the neonatal period. They are promising target diseases for liver cell transplantation (LCT), which may be a less invasive alternative or supplementation to orthotopic liver transplantation. METHODS: Cryopreserved hepatocytes were isolated under good manufacturing practice conditions. Four children with severe neonatal UCD (age 1 day-3 years) received multiple intraportal infusions of cryopreserved hepatocytes from that same donor, a 9-day old neonate. Portal vein access was achieved surgically in two children, whereas the umbilical vein was suitable for interventional catheter placement in two neonates. Cell applications were carefully monitored by means of Doppler ultrasound and portal vein pressure. RESULTS: LCT was feasible in all children. No signs of portal vein thrombosis or extrahepatic shunting were observed. All children showed metabolic stabilization during observation periods of 4 to 13 months. One child with prenatally diagnosed ornithine transcarbamylase deficiency died after 4 months from a fatal metabolic decompensation. CONCLUSIONS: Given the poor prognosis of UCD with conservative therapy, LCT caused considerable beneficial effects. Periods of hyperammonemia and clinically relevant crises could be reduced during an observation period of up to 13 months. Though cell therapy is not a permanent therapeutic option, bridging to liver transplantation may be substantially improved.


Assuntos
Transplante de Células/métodos , Hepatócitos/transplante , Transplante de Fígado/métodos , Doença da Deficiência de Ornitina Carbomoiltransferase/cirurgia , Ureia/metabolismo , Amônia/sangue , Criopreservação , Humanos , Lactente , Recém-Nascido , Veia Porta/cirurgia , Doadores de Tecidos , Resultado do Tratamento
15.
Bioanalysis ; 1(9): 1527-35, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21083101

RESUMO

We demonstrate the effective use of NMR spectroscopic profiles of urine and plasma from the first successful use of hepatocyte transplantation as a bridge to auxiliary partial orthotopic liver transplantation in a child antenatally diagnosed with severe ornithine transcarbamylase deficiency. In this single-patient study, NMR profiles indicated that the disrupted urea cycle could be normalized by hepatocyte cell infusion and this was confirmed using orthogonal partial least-squares-based chemometrics. However, despite dietary manipulations and adminstration of ammonia scavengers, the desired reduction in plasma ammonia was not consistently achieved between sessions of hepatocyte transplantation due to episodes of sepsis. A subsequent liver transplant corrected the metabolic abnormalities. The use of metabolic profiling has been shown to be a promising method for evaluating the efficacy of cell infusions and has demonstrated the capability for the early detection of response to therapy in real time, an approach that may be of use in wider clinical settings.


Assuntos
Hepatócitos/transplante , Metabolômica/métodos , Monitorização Fisiológica/métodos , Doença da Deficiência de Ornitina Carbomoiltransferase/cirurgia , Amônia/sangue , Amônia/urina , Hepatócitos/fisiologia , Humanos , Lactente , Recém-Nascido , Transplante de Fígado , Espectroscopia de Ressonância Magnética , Masculino , Mutação , Doença da Deficiência de Ornitina Carbomoiltransferase/sangue , Doença da Deficiência de Ornitina Carbomoiltransferase/urina , Sepse/sangue , Sepse/diagnóstico , Sepse/urina , Resultado do Tratamento , Ureia/sangue , Ureia/urina
16.
Am J Transplant ; 8(2): 452-7, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18211511

RESUMO

We report the first successful use of hepatocyte transplantation as a bridge to subsequent auxiliary partial orthotopic liver transplantation (APOLT) in a child antenatally diagnosed with severe ornithine transcarbamylase (OTC) deficiency. A total of 1.74 x 10(9) fresh and cryopreserved hepatocytes were administered intraportally into the liver over a period of 6 months. Immunosuppression was with tacrolimus and prednisolone. A sustained decrease in ammonia levels and a gradual increase in serum urea were observed except during episodes of sepsis in the first 6 months of life. The patient was able to tolerate a normal protein intake and presented a normal growth and neurological development. APOLT was successfully performed at 7 months of age. We conclude that hepatocyte transplantation can be used in conjunction with APOLT as an effective treatment for severe OTC-deficient patients, improving neurodevelopmental outcomes.


Assuntos
Hepatócitos/transplante , Transplante de Fígado , Doença da Deficiência de Ornitina Carbomoiltransferase/cirurgia , Doença da Deficiência de Ornitina Carbomoiltransferase/terapia , Adolescente , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Diagnóstico Pré-Natal , Resultado do Tratamento
17.
Surg Today ; 35(12): 1087-91, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16341494

RESUMO

We report the case of a 7-year-old girl with ornithine transcarbamylase deficiency whose quality of life (QOL) improved greatly after a living donor liver transplantation (LDLT). Ornithine transcarbamylase deficiency had been diagnosed when she was 2 years old and she finally underwent LDLT, with her father as the donor, when she was 7 years old. The patient had suffered episodes of hyperammonemic encephalopathy ranging from lethargy to coma, treated by hemodialysis twice before LDLT, and her intelligence quotient was borderline for her age. Preoperative magnetic resonance imaging (MRI) showed an atrophic area in the subcortical white matter of the frontal lobe. After LDLT, the patient suffered acute rejection with hyperamylasemia, but not hyperammonemia. Postoperative MRI and quantitative MR spectroscopy showed no changes in the subcortical lesion. She has been followed up carefully for 16 months and has had no further complications or any sign of hyperammonemia.


Assuntos
Encéfalo/patologia , Transplante de Fígado , Doença da Deficiência de Ornitina Carbomoiltransferase/cirurgia , Qualidade de Vida , Atrofia , Criança , Feminino , Humanos , Doadores Vivos , Imageamento por Ressonância Magnética
18.
J Formos Med Assoc ; 104(9): 623-9, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16276436

RESUMO

BACKGROUND AND PURPOSE: Liver transplantation could be a useful treatment for selected inborn errors of metabolism. This study evaluated the outcome and viral infections after liver transplantation in young children and infants with these diseases. METHODS: The outcome of liver transplantation and clinical characteristics of the following 4 patients were assessed: 1 infant with ornithine transcarbamylase deficiency (OTCD) who received liver transplant aged 3 years and 4 months; 1 infant with carbamyl phosphate synthetase I deficiency (CPSID) who received liver transplant at 14 months of age; and 2 infants with methylmalonic acidemia (MMA) who received liver transplant at 8 months and 11 months of age, respectively. All donors, except the 8-month-old infant with MMA, showed serologic evidence of previous cytomegalovirus (CMV) infection before transplantation. All 4 of these donors showed serologic evidence of previous infection of Epstein-Barr virus (EBV). None of the recipients had previous CMV infection. Both the infant with OTCD and the 8-month-old infant with MMA had previous EBV infection, while the other 2 patients did not. Preoperative hemodialysis was performed in both infants with MMA. Postoperative follow-up included metabolic stability, disability degree, and viral infections. RESULTS: None of the patients developed severe metabolic decompensation after transplantation and all increased protein intake postoperatively. Symptomatic viral infections, however, were present in all patients postoperatively, including CMV infection in the infant with OTCD and the 11-month-old infant with MMA, reactivation of EBV infection in the infant with OTCD and the 8-month-old infant with MMA, and primary EBV infection in the infant with CPSID. CONCLUSIONS: Liver transplantation was an effective treatment for all 4 of these patients with inborn errors of metabolism. The risk of symptomatic viral infections for these patients was high. This was likely associated with conditions including immunosuppression, young age, endemic nature of CMV and EBV infections, and lack of CMV prophylaxis.


Assuntos
Infecções por Citomegalovirus/etiologia , Infecções por Vírus Epstein-Barr/etiologia , Febre/etiologia , Transplante de Fígado/efeitos adversos , Erros Inatos do Metabolismo/cirurgia , Complicações Pós-Operatórias/etiologia , Doença da Deficiência da Carbamoil-Fosfato Sintase I/cirurgia , Pré-Escolar , Humanos , Lactente , Ácido Metilmalônico/urina , Doença da Deficiência de Ornitina Carbomoiltransferase/cirurgia
19.
Liver Transpl ; 11(11): 1332-42, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16237708

RESUMO

To address the current role of liver transplantation (LT) for urea cycle disorders (UCDs), we reviewed the worldwide English literature on the outcomes of LT for UCD as well as 13 of our own cases of living donor liver transplantation (LDLT) for UCD. The total number of cases was 51, including our 13 cases. The overall cumulative patient survival rate is presumed to be more than 90% at 5 years. Most of the surviving patients under consideration are currently doing well with satisfactory quality of life. One advantage of LDLT over deceased donor liver transplantation (DDLT) is the opportunity to schedule surgery, which beneficially affects neurological consequences. Auxiliary partial orthotopic liver transplantation (APOLT) is no longer considered significant for the establishment of gene therapies or hepatocyte transplantation but plays a significant role in improving living liver donor safety; this is achieved by reducing the extent of the hepatectomy, which avoids right liver donation. Employing heterozygous carriers of the UCDs as donors in LDLT was generally acceptable. However, male hemizygotes with ornithine transcarbamylase deficiency (OTCD) must be excluded from donor candidacy because of the potential risk of sudden-onset fatal hyperammonemia. Given this possibility as well as the necessity of identifying heterozygotes for other disorders, enzymatic and/or genetic assays of the liver tissues in cases of UCDs are essential to elucidate the impact of using heterozygous carrier donors on the risk or safety of LDLT donor-recipient pairs. In conclusion, LT should be considered to be the definitive treatment for UCDs at this stage, although some issues remain unresolved.


Assuntos
Causas de Morte , Rejeição de Enxerto/epidemiologia , Transplante de Fígado/métodos , Doença da Deficiência de Ornitina Carbomoiltransferase/diagnóstico , Doença da Deficiência de Ornitina Carbomoiltransferase/cirurgia , Ureia/metabolismo , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Sobrevivência de Enxerto , Humanos , Incidência , Lactente , Recém-Nascido , Japão , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Probabilidade , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Estatísticas não Paramétricas , Taxa de Sobrevida , Doadores de Tecidos
20.
Leuk Lymphoma ; 46(7): 1057-60, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16019558

RESUMO

Organ transplant recipients are generally considered to be at greater risk for developing malignant disorders because of prolonged immunosuppression for organ grafting, but acute leukemia is a rare complication after organ transplantation (0.2 -2.5%). We encountered two girls with acute promyelocytic leukemia (APL) after living donor partial orthotopic liver transplantation. In one patient, APL developed 21 months after liver transplantation for ornithine transcarbamylase deficiency. She had been administered tacrolimus for prophylaxis of graft-versus-host reaction. In the other patient, APL was diagnosed 46 months after liver transplantation for congenital biliary atresia. Both patients were successfully treated by chemotherapy including all-trans retinoic acid (ATRA), and after reaching complete remission, they have subsequently been in continuous remission. Although leukemia after liver transplantation is generally thought of as a rare complication, increases in survival rate following liver transplantation is likely to lead to more such cases, and documentation of these cases is therefore of importance.


Assuntos
Leucemia Promielocítica Aguda/etiologia , Transplante de Fígado/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Atresia Biliar/cirurgia , Criança , Pré-Escolar , Citarabina/administração & dosagem , Daunorrubicina/administração & dosagem , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Imunossupressores/administração & dosagem , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/patologia , Doadores Vivos , Doença da Deficiência de Ornitina Carbomoiltransferase/cirurgia , Indução de Remissão , Tacrolimo/administração & dosagem , Tretinoína/administração & dosagem
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