Data on items of AKUSSI in Alkaptonuria collected over three years from the United Kingdom National Alkaptonuria Centre and the impact of nitisinone

Griffin, Rebecca; Psarelli, EE; Cox, TF; Khedr, Milad; Milan, Anna M.; Davison, Andrew S.; Hughes, Andrew T.; Usher, J.; Taylor, Sophie; Loftus, Nadia; Daroszewska, Anna; West, Elizabeth A.; Jones, A. S.; Briggs, Michael; Fisher, Michael; McCormick, M; Judd, Shirley; Vinjamuri, Sobhan; Sireau, Nicolas; Dillon, J.P.; Devine, J.; Hughes, Georgina; Harrold, Joanne A.; Barton, Gábor; Jarvis, JC; Gallagher, J.A.; Ranganath, L.R.

doi:10.1016/j.dib.2018.09.021

Cited by 15 publications

(33 citation statements)

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“…This could at least partly be explained as the aim in TT1 is to have no activity of 4HPPD at all, while this is different in AKU. Although this low dose of NTBC initially failed to show a response on non-biochemical outcomes [60], a decrease in clinical progression of eye and ear ochronosis in AKU patients has recently been reported [62, 63]. It is not known whether long-term NTBC treatment in AKU is effective, neither is it known whether NTBC could prevent the severe bone disease caused by ochronosis in AKU patients if started early.…”

Section: Ntbc Treatment In Other Disorders Of Tyrosine Metabolismmentioning

confidence: 99%

Long-Term Outcomes and Practical Considerations in the Pharmacological Management of Tyrosinemia Type 1

et al. 2019

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Tyrosinemia type 1 (TT1) is a rare metabolic disease caused by a defect in tyrosine catabolism. TT1 is clinically characterized by acute liver failure, development of hepatocellular carcinoma, renal and neurological problems, and consequently an extremely poor outcome. This review showed that the introduction of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) in 1992 has revolutionized the outcome of TT1 patients, especially when started pre-clinically. If started early, NTBC can prevent liver failure, renal problems, and neurological attacks and decrease the risk for hepatocellular carcinoma. NTBC has been shown to be safe and well tolerated, although the long-term effectiveness of treatment with NTBC needs to be awaited. The high tyrosine concentrations caused by treatment with NTBC could result in ophthalmological and skin problems and requires lifelong dietary restriction of tyrosine and its precursor phenylalanine, which could be strenuous to adhere to. In addition, neurocognitive problems have been reported since the introduction of NTBC, with hypothesized but as yet unproven pathophysiological mechanisms. Further research should be done to investigate the possible relationship between important clinical outcomes and blood concentrations of biochemical parameters such as phenylalanine, tyrosine, succinylacetone, and NTBC, and to develop clear guidelines for treatment and follow-up with reliable measurements. This all in order to ultimately improve the combined NTBC and dietary treatment and limit possible complications such as hepatocellular carcinoma development, neurocognitive problems, and impaired quality of life. Key Points Treatment with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) has been found to be generally safe and has clearly improved treatment and outcomes for patients with tyrosinemia type 1.

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Section: Ntbc Treatment In Other Disorders Of Tyrosine Metabolismmentioning

confidence: 99%

Long-Term Outcomes and Practical Considerations in the Pharmacological Management of Tyrosinemia Type 1

et al. 2019

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“…Nitisinone therapy in the NAC, and in the NIH, decreased serum and urine HGA by over 95%, offering for all practical purposes a "biochemical" cure of AKU. [19][20][21][22] The aim of the study discussed further in this manuscript was to examine the effect of nitisinone on the ochronotic process in photographs of the eyes and ears, as well as in ear cartilage biopsies taken four years apart, in patients attending the NAC.…”

Section: Introductionmentioning

confidence: 99%

Reversal of ochronotic pigmentation in alkaptonuria following nitisinone therapy: Analysis of data from the United Kingdom National Alkaptonuria Centre

et al. 2020

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Background Increased homogentisic acid (HGA) causes ochronosis. Nitisinone decreases HGA. The aim was to study the effect of nitisinone on the ochronosis progression. Methods Photographs of the eyes and ears were acquired from patients attending the National Alkaptonuria Centre (NAC) at V‐1 (pre‐baseline visit), V0 (baseline visit when 2 mg nitisinone was commenced), and yearly at V1, V2, and V3 visits. Photographs were inspected for evolution of ochronotic pigment and also scored categorically to derive eye, ear, and combined ochronosis scores. An ear cartilage biopsy was also carried out at V0 and one year after V3 (V4) and ochronotic pigment was assessed and quantitated. Visits were compared for changes in pigment. Fasting blood and 24‐hour urine samples were collected for measurement of HGA. Results There were 80 AKU patients at V0, and 52, 47, and 40 at V1, V2, and V3 in the group with variable numbers (VAR Group) respectively; 23 patients attended once before V0, in the V‐1 visit. Photographs of patients show increase in eye pigment between V‐1 and V0, followed by decrease post‐nitisinone at V1, V2, and V3. Ear and combined ochronosis semiquantitative scoring showed an increase between V‐1 and V0 (P < .01), followed by a decrease at V1, V2, and V3, in the VAR group (P < .01). Ochronotic pigment in ear biopsy between V0 and V4 showed a 19.1% decrease (P < .05). Conclusions Nitisinone decreases HGA and partially reverses ochronosis.

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“…As AKU research has gathered traction and more patients have become involved in research, the AKUSSI has clearly demonstrated the effect of nitisinone on the various parameters of the index. It shows how effective the therapy is, adding further validation to its use in AKU, it reduces HGA but also demonstrates numerous secondary important features of monitoring patients and their tissues which become symptomatic during the course of the disease [77,78]. The efficacy of nitisinone is clearer seen in longitudinal studies spanning 3 years examining multiple patients with AKU, not only reducing HGA, but also arresting ocular and auricular ochronosis [59].…”

Section: Effectiveness Of Nitisinone In Akumentioning

confidence: 91%

The potential of nitisinone for the treatment of alkaptonuria

Taylor

Shepherd

2019

Expert Opinion on Orphan Drugs

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Introduction: Alkaptonuria is an iconic disease, dating back to the Egyptians and has continued to prove a valuable teaching tool to many medics as an example of an inborn error of metabolism. In recent years, much progress has been made on understanding the condition and its symptoms; the single defective gene has been identified and cloned. In humans novel phenotypic presentations of the condition have been documented, and in vitro models developed to understand the disease. Furthermore, a mouse model has studied and most recently clinical trials into the effectiveness of nitisinone have been undertaken. Nitisinone has been on a miraculous journey from its discovery as a weed killer to its effective treatment in hereditary tyrosinaemia type-1. Areas covered: The authors describe research into nitisinone and its application in model and human systems in both hereditary tyrosinaemia type 1 (HTT-1) and Alkaptonuria. The published literature was searched for outputs relating to "Alkaptonuria", "ochronosis", "nitisinone", "hereditary tyrosinaemia type 1". Any paper not in English or had no translation were excluded. Expert opinion: Now nitisinone is being studied for use in Alkaptonuria and this paper documents the journey of AKU and the promising potential of nitisinone in the treatment of Alkaptonuria.

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Data on items of AKUSSI in Alkaptonuria collected over three years from the United Kingdom National Alkaptonuria Centre and the impact of nitisinone

Cited by 15 publications

References 1 publication

Long-Term Outcomes and Practical Considerations in the Pharmacological Management of Tyrosinemia Type 1

Long-Term Outcomes and Practical Considerations in the Pharmacological Management of Tyrosinemia Type 1

Reversal of ochronotic pigmentation in alkaptonuria following nitisinone therapy: Analysis of data from the United Kingdom National Alkaptonuria Centre

The potential of nitisinone for the treatment of alkaptonuria

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