Severe neurological crisis in adult patients with Tyrosinemia type 1.
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ABSTRACT:
SUBMITTER: Dawson C
PROVIDER: S-EPMC7480904 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
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Severe neurological crisis in adult patients with Tyrosinemia type 1.
Dawson Charlotte C Ramachandran Radha R Safdar Samreen S Murphy Elaine E Swayne Orlando O Katz Jonathan J Newsome Philip N PN Geberhiwot Tarekegn T Geberhiwot Tarekegn T
Annals of clinical and translational neurology 20200821 9
We report six adult patients with Tyrosinaemia type 1 (HT-1) who presented with recurrent porphyria-like neurological crises after discontinuation/interruption of 2-(2-nitro-4-trifluoro-methylbenzyol)-1,3 cyclohexanedione (NTBC) treatment. The crises were life-threatening for some of the patients, with respiratory muscle paralysis requiring ventilatory support, hemodynamic disturbance due to autonomic changes requiring resuscitation, acute progressive ascending motor neuropathy causing profound ...[more]
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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.
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Project description:Background/Objective: The changes to medical studies that became necessary as part of the Corona pandemic have also forced considerable adjustments in Neurology. Classroom teaching had to be converted almost entirely to digital formats within a short period of time. The present study provides an overview of the respective changes and associated complications as well as opportunities in teaching Neurology. Methodology: Lecturers in Neurology at all University hospitals in Germany were asked about their approach and the individual changes in their curriculum. Of a total of 39 locations, 23 answered the online questionnaire (see attachment 1). Results: While frontal teaching and lectures could be carried out digitally without any problems, difficulties arose especially in learning physical examination and bedside teaching. Most of the participants stated that they had not found satisfactory e-learning formats to replace teaching at the patients bed. Conclusion: The ad hoc changes in teaching Neurology resulted in significant additional effort for the part of lecturers, but were generally well accepted by students. The Corona pandemic thus ultimately offers an opportunity to enrich teaching in Neurology.
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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.
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Project description:BackgroundTyrosinemia type 1 (hepatorenal tyrosinemia, HT1) is a rare autosomal recessive inborn error of tyrosine metabolism caused by deficiency of the last enzyme in the tyrosine catabolic pathway, fumarylacetoacetate hydrolase (FAH) leading to severe hepatic, renal and peripheral nerve damage if left untreated. Early treatment may prevent acute liver failure, renal dysfunction, liver cirrhosis, hepatocellular carcinoma (HCC) and improves survival.Material and methodsA retrospective single center study was carried out based on the clinical and biochemical presentation, therapy and outcome of 25 Palestinian patients with HT1 diagnosed during the last 25 years.ResultsHT1 is not included in newborn screening program in Palestine. The mean age at diagnosis was 8 months and the main clinical manifestations were coagulopathy, hepatomegaly, splenomegaly and renal tubular dysfunction. The main biochemical abnormalities were elevated plasma tyrosine, serum transaminases and prothrombin time, and low serum phosphorous with elevated alkaline phosphatase compatible with hypophosphatemic rickets secondary to renal tubular dysfunction. All patients were treated with nitisinone. The mean duration of nitisinone treatment was 74 months and the mean dosage was 0.89 mg/kg/day. None developed HCC or neurological crisis.ConclusionsMost patients present with liver failure and renal tubular dysfunction. Nitisinone treatment was effective therapy in all patients and improved both short- and long-term prognosis of HT1. Renal tubular dysfunction improved in all patients within the first week of starting nitisinone. Early diagnosis is necessary because delay in the treatment increases the risk of progressive liver failure HCC, progressive renal disease and neuropathy.
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Project description:Phenylketonuria (PKU) is treated with dietary restrictions and sometimes tetrahydrobiopterin (BH4). PKU patients are at risk for developing micronutrient deficiencies, such as vitamin B12 and folic acid, likely due to their diet. Tyrosinemia type 1 (TT1) is similar to PKU in both pathogenesis and treatment. TT1 patients follow a similar diet, but nutritional deficiencies have not been investigated yet. In this retrospective study, biomarkers of micronutrients in TT1 and PKU patients were investigated and outcomes were correlated to dietary intake and anthropometric measurements from regular follow-up measurements from patients attending the outpatient clinic. Data was analyzed using Kruskal-Wallis, Fisher's exact and Spearman correlation tests. Furthermore, descriptive data were used. Overall, similar results for TT1 and PKU patients (with and without BH4) were observed. In all groups high vitamin B12 concentrations were seen rather than B12 deficiencies. Furthermore, all groups showed biochemical evidence of vitamin D deficiency. This study shows that micronutrients in TT1 and PKU patients are similar and often within the normal ranges and that vitamin D concentrations could be optimized.
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