Hepatorenal tyrosinemia.
Ontology highlight
ABSTRACT:
SUBMITTER: Kitagawa T
PROVIDER: S-EPMC3410490 | biostudies-literature | 2012
REPOSITORIES: biostudies-literature
Publications
Hepatorenal tyrosinemia.
Proceedings of the Japan Academy. Series B, Physical and biological sciences 20120101 5
In 1957 Sakai and Kitagawa in Japan reported the clinical and biochemical findings in a patient with tyrosinemia, tyrosyluria, liver cirrhosis, and renal rickets. Subsequently, reports were published from various countries of other patients with hepatorenal tyrosinemia (HRT). 4-Hydroxyphenylpyruvate dioxygenase deficiency was originally proposed as the cause of HRT. However, in 1977 Lindblad et al. found that succinylacetone, which accumulates in the serum and urine from patients with HRT, inhib ...[more]
Similar Datasets
Project description:Hepatorenal syndrome (HRS) is the most serious hepatorenal disorder and one of the most difficult to treat. To date, the best treatment options are those that reverse the mechanisms underlying HRS: portal hypertension, splanchnic vasodilation, and/or renal vasoconstriction. Therefore, liver transplantation is the preferred definitive treatment option. The role of other therapies is predominantly to prolong survival sufficiently to allow patients to undergo transplantation. Terlipressin with the addition of adjunctive albumin volume expansion is the preferred pharmacologic therapy for the treatment of patients with HRS. Norepinephrine and vasopressin are acceptable alternatives in countries where terlipressin is not yet available. For patients with Type II HRS, midodrine plus octreotide appears to be an effective pharmacologic regimen that can be administered outside of an intensive care unit setting. Regardless of chosen vasoconstrictor therapy, careful monitoring is needed to ensure tissue ischemia and severe adverse effects do not occur. Artificial hepatic support devices, renal replacement therapy, and transjugular intrahepatic portosystemic shunt (TIPS) are non-pharmacologic options for patients with HRS. However, hepatic support devices and renal replacement therapies have not yet demonstrated improved outcomes and TIPS is difficult to be employed in patients with Type I HRS due to contraindications in the majority of patients. Despite advances in our understanding of hepatorenal syndrome, the disease is still associated with significant morbidity, mortality, and costs. More evidence is urgently needed to help improve patient outcomes in this difficult-to-treat population.
| S-EPMC7153775 | biostudies-literature
Project description:Tyrosinemia type 3 (HT3) is a rare inborn error of tyrosine metabolism caused by mutations in the HPD gene encoding 4-hydroxyphenyl-pyruvate dioxygenase, which is transmitted in an autosomal recessive trait. The disorder is characterized by tyrosine accumulation in body fluids and massive excretion of tyrosine derivatives into urine (www.orpha.net). Since it is the least frequent form of tyrosinemia, only few cases with the variable but rather mild clinical features have been described so far. We report an 11 year old girl presenting with no clinical symptoms and with normal mental development who has been diagnosed with HT3 through metabolic screening on the basis of elevated serum level of tyrosine ranging from 425 to 535 ?mol/L (normal values: 29-86 ?mol/L), and elevated urinary excretion of p-hydroxyphenyl derivatives confirmed genetically with the homozygous c.479A > G (p.Tyr160Cys) missense change in the HPD gene. The girl has been only presenting with recurrent proteinuria of unknown etiology. A phenylalanine- and tyrosine-restricted diet has never been administered. Presented case may suggest that high tyrosine concentration itself does not participate directly in neuronal damage described in patients with tyrosinemia type 3.
| S-EPMC5471395 | biostudies-literature
Project description:BackgroundWhile therapeutic advances have significantly improved the prognosis of patients with hereditary tyrosinemia type 1 (HT1), adherence to dietary and pharmacological treatments is essential for an optimal clinical outcome. Poor treatment adherence is well documented among patients with chronic diseases, but data from HT1 patients are scarce. This study evaluated pharmacological and dietary adherence in HT1 patients both directly, by quantifying blood levels nitisinone (NTBC) levels and metabolic biomarkers of HT1 [tyrosine (Tyr), phenylalanine (Phe), and succinylacetone]; and indirectly, by analyzing NTBC prescriptions from hospital pharmacies and via clinical interviews including the Haynes-Sackett (or self-compliance) test and the adapted Battle test of patient knowledge of the disease.ResultsThis observational study analyzed data collected over 4 years from 69 HT1 patients (7 adults and 62 children; age range, 7 months-35 years) who were treated with NTBC and a low-Tyr, low-Phe diet. Adherence to both pharmacological and, in particular, dietary treatment was poor. Annual data showed that NTBC levels were lower than recommended in more than one third of patients, and that initial Tyr levels were high (> 400 µM) in 54.2-64.4% of patients and exceeded 750 µM in 25.8% of them. Remarkably, annual normalization of NTBC levels was observed in 29.4-57.9% of patients for whom serial NTBC determinations were performed. Poor adherence to dietary treatment was more refractory to positive reinforcement: 36.2% of patients in the group who underwent multiple analyses per year maintained high Tyr levels during the entire study period, and, when considering each of the years individually this percentage ranged from 75 to 100% of them. Indirect methods revealed percentages of non-adherent patients of 7.3 and 15.9% (adapted Battle and Haynes tests, respectively).ConclusionsDespite initially poor adherence to pharmacological and especially dietary treatment among HT1 patients, positive reinforcement at medical consultations resulted in a marked improvement in NTBC levels, indicating the importance of systematic positive reinforcement at medical visits.
| S-EPMC8173906 | biostudies-literature
Project description:The hepatorenal fibrocystic (HRFC) syndromes are a heterogeneous group of severe monogenic conditions that may be detected before birth. Commonly, HRFC syndromes present in the neonatal and paediatric age, with consistent developmental abnormalities mostly involving the liver and kidney. The changes include the proliferation and dilatation of epithelial ducts in these tissues with abnormal deposition of extracellular matrix. In this review, we examine the clinical features and differential diagnoses of this group of syndromes, including autosomal recessive polycystic kidney disease (ARPKD), juvenile nephronophthisis (NPHP), Meckel-Gruber syndrome (MKS), Bardet-Biedl syndrome (BBS), and Jeune asphyxiating thoracic dystrophy (JATD). Extrahepatic manifestations include mostly bone and central nervous system abnormalities, dysmorphic features, and developmental delay. Previously, it has been suggested that ARPKD, JATD, and Ellis-van Creveld syndrome (EvC) may arise from defects in differentiation in a common developmental pathway. We review recent molecular advances in the recessive HRFC syndromes and discuss this hypothesis.
| S-EPMC1735460 | biostudies-other
Project description:Tyrosinemia type 1 (HT1) is an inborn error of tyrosine catabolism caused by fumarylacetoacetase deficiency. Biochemically, this results in accumulation of toxic metabolites including succinylacetone. Clinically, HT1 is characterized by severe liver, kidney, and neurological problems. Treatment with NTBC and dietary restriction of tyrosine and phenylalanine have strongly improved outcome, but impaired neurocognitive development has been reported. Whether impaired neurocognitive outcome results from high blood tyrosine or low blood phenylalanine concentrations is currently unknown. In this report, two HT1 newborns, diagnosed by neonatal screening, are presented. The first patient showed low phenylalanine concentrations, growth retardation, neurological impairments, and skin problems, clearly improving after institution of phenylalanine supplementation (~30 mg/kg/day) at age 6 months, while both blood phenylalanine and tyrosine concentrations increased. In the second patient, phenylalanine supplementation (~20 mg/kg/day) was initiated as soon as low phenylalanine concentrations were observed at age 19 days. On this regimen, blood phenylalanine concentrations increased, and hypophenylalaninemia was less frequently observed than in the first patient, whereas blood tyrosine concentrations tended to increase. Clinically, no growth, neurological, or skin problems have been observed. The combination of knowledge obtained from these cases suggests that hypophenylalaninemia rather than hypertyrosinemia during the first months of life may impair neurocognitive development in young HT1 infants. Phenylalanine supplementation should really be considered in HT1 patients with consistently low blood phenylalanine concentrations during the first months of life. However, the minimal phenylalanine concentrations acceptable and the optimal phenylalanine supplementation regimen require further investigation.
| S-EPMC4361924 | biostudies-literature
Project description:Neurometabolic disorders such as tyrosinemia type 1 (TYRSN1) may interfere with brain metabolism and show symptoms of attention-deficit hyperactivity disorder (ADHD) in patients treated with the enzyme inhibitor nitisinone [2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione, NTBC]. It has been reported that ADHD treatment improves treatment compliance, which is imperative for the long-term prognosis of patients with TYRSN1. In this study, we report the case of a male patient who was diagnosed with TYRSN1 at 3 months of age and was subsequently treated with NTBC, restricted protein intake, and amino acids supplementation. At 7 years of age, he was referred for neuropsychiatric assessment, diagnosed with ADHD, and treated with methylphenidate. The effects of the treatment were monitored via parental interviews, questionnaires covering ADHD symptoms, and a continuous performance test. A reduction in ADHD symptoms, particularly inattentiveness, was observed across all measures. The early identification of ADHD and the treatment of neurometabolic disorders, such as TYRSN1, may be important from a lifetime perspective as this may improve the prognosis of the medical condition as well.
| S-EPMC10392124 | biostudies-literature
Project description:BackgroundThe spectrum of disorders associated with hyperinsulinemic hypoglycemia (HHI) has vastly increased over the past 20 years with identification of molecular, metabolic and cellular pathways involved in the regulation of insulin secretion and its actions. Hereditary tyrosinemia (HT1) is a rare metabolic disorder associated with accumulation of toxic metabolites of the tyrosine pathway due to a genetically mediated enzyme defect of fumarylacetoacetate hydrolase. Transient tyrosinemia of the newborn (TTN) is a benign condition with a maturational defect of the enzymes associated with tyrosine metabolism without any genetic abnormalities.ResultsWe describe two rare cases of HHI, one in a patient with HT1 and for the first time, in a patient with TTN. Each of our patients presented in the neonatal period with persistent hypoglycemia that on biochemical evaluation was consistent with HHI. Each patient received diazoxide therapy for 3.5 months and 17 months of life, respectively and HHI resolved thereafter.ConclusionDespite the fact that HHI has been described in HT1 for several decades, no specific mechanism has been delineated. Although we considered the common embryonal origin of the liver and pancreas with the hepatotoxic effect in HT1 also impacting the latter, this was not a possible explanation for TTN. The commonality between our two patients is the accumulation of certain amino acids which are known to be insulinotropic. We therefore hypothesize that the excess of amino acids such as leucine, lysine, valine and isoleucine in our patients resulted in HHI, which was transient. Both patients responded to diazoxide. This novel presentation in TTN and the reassuring response in both HT1 and TTN to diazoxide will be useful to inform physicians about managing HHI in these patients. Further studies are required to delineate the mechanism of HHI in these infants.
| S-EPMC8082838 | biostudies-literature
Project description:Efficient detoxification and clearance of cholesterol metabolites such as oxysterols, bile alcohols, and bile acids are critical for survival because they can promote liver and cardiovascular disease. We report here that loss of the nuclear xenobiotic receptor PXR (pregnane X receptor), a regulator of enterohepatic drug metabolism and clearance, results in an unexpected acute lethality associated with signs of severe hepatorenal failure when mice are fed with a diet that elicits accumulation of cholesterol and its metabolites. Induction of a distinct drug clearance program by a high-affinity ligand for the related nuclear receptor, the constitutive androstane receptor, does not overcome the lethality, indicating the unique requirement of PXR for detoxification. We propose that the PXR signaling pathway protects the body from toxic dietary cholesterol metabolites, and, by extension, PXR ligands may ameliorate human diseases such as cholestatic liver diseases and the associating acute renal failure.
| S-EPMC548561 | biostudies-literature
Project description:OBJECTIVE:Hepatorenal Syndrome (HRS) is a devastating form of acute kidney injury (AKI) in advanced liver disease patients with high morbidity and mortality, but phenotyping algorithms have not yet been developed using large electronic health record (EHR) databases. We evaluated and compared multiple phenotyping methods to achieve an accurate algorithm for HRS identification. MATERIALS AND METHODS:A national retrospective cohort of patients with cirrhosis and AKI admitted to 124 Veterans Affairs hospitals was assembled from electronic health record data collected from 2005 to 2013. AKI was defined by the Kidney Disease: Improving Global Outcomes criteria. Five hundred and four hospitalizations were selected for manual chart review and served as the gold standard. Electronic Health Record based predictors were identified using structured and free text clinical data, subjected through NLP from the clinical Text Analysis Knowledge Extraction System. We explored several dimension reduction techniques for the NLP data, including newer high-throughput phenotyping and word embedding methods, and ascertained their effectiveness in identifying the phenotype without structured predictor variables. With the combined structured and NLP variables, we analyzed five phenotyping algorithms: penalized logistic regression, naïve Bayes, support vector machines, random forest, and gradient boosting. Calibration and discrimination metrics were calculated using 100 bootstrap iterations. In the final model, we report odds ratios and 95% confidence intervals. RESULTS:The area under the receiver operating characteristic curve (AUC) for the different models ranged from 0.73 to 0.93; with penalized logistic regression having the best discriminatory performance. Calibration for logistic regression was modest, but gradient boosting and support vector machines were superior. NLP identified 6985 variables; a priori variable selection performed similarly to dimensionality reduction using high-throughput phenotyping and semantic similarity informed clustering (AUC of 0.81 - 0.82). CONCLUSION:This study demonstrated improved phenotyping of a challenging AKI etiology, HRS, over ICD-9 coding. We also compared performance among multiple approaches to EHR-derived phenotyping, and found similar results between methods. Lastly, we showed that automated NLP dimension reduction is viable for acute illness.
| S-EPMC5920557 | biostudies-literature
Project description:IntroductionUltrasonography is widely used as the first tool to evaluate fatty liver disease, and the hepatorenal index is a semi-quantitative method that improves its performance. Fibrosis can co-exist with steatosis or even replace it during disease progression. This study aimed to evaluate the influence of fibrosis on the measurement of steatosis using the hepatorenal index.Materials and methodsThis cross-sectional study included 89 patients with nonalcoholic fatty liver disease and in whom liver fibrosis was determined by ultrasound elastography. The Pearson's correlation coefficient was used to compare between the results of the sonographic hepatorenal index and the quantification of steatosis using magnetic resonance spectroscopy as well the accuracy of detecting moderate to severe steatosis using sonography in two groups of patients: (A) without advanced fibrosis and (B) with advanced fibrosis. Advanced fibrosis was defined as a shear wave speed ≥ 1.78 m/s on ultrasound elastography. We calculated the area under the curve (AUC-ROC) to detect the ability of the hepatorenal index to differentiate light from moderate to severe steatosis in both groups. Moderate to severe steatosis was defined as a fat fraction > 15% on the magnetic resonance spectroscopy. The intra-observer variability was assessed using the Bland-Altman plot.ResultsAmong patients, the mean age was 54.6 years and 59.6% were women, 50.6% had a body mass index ≥ 30 kg/m2, 29.2% had moderate to severe steatosis, and 27.2% had advanced fibrosis. There was a correlation between steatosis grading by ultrasonography and magnetic resonance in group A (0.73; P < 0.001), but not in Group B (0.33; P = 0.058). The AUC-ROC for detecting a steatosis fraction ≥ 15% was 0.90 and 0.74 in group A and group B, respectively. The intra-observer variability for the hepatorenal index measurements was not significant (-0.036; P = 0.242).ConclusionThe hepatorenal index is not appropriate for estimating steatosis in livers with advanced fibrosis.
| S-EPMC7880490 | biostudies-literature