Suitability of nitisinone for alkaptonuria

Häberle, Johannes

doi:10.1016/s2213-8587(20)30222-9

Cited by 7 publications

(5 citation statements)

References 8 publications

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“…The objective of this manuscript is to compare the efficacy and specific aspects of safety of nitisinone 2 mg daily with 10 mg daily, in order to guide nitisinone dosing in AKU, an issue also raised in a recently published communication. 16 between 2007 and 2020. Attendance between 2007 and 2011, a single non-interventional visit (VR), was part of a research study (Natural History study in alkaptonuria; UK Research Ethics Committee Number 07/Q1002/111).…”

Section: Introductionmentioning

confidence: 99%

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Comparing nitisinone 2 mg and 10 mg in the treatment of alkaptonuria—An approach using statistical modelling

et al. 2021

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Background: Outcomes from studies employing nitisinone 10 mg and 2 mg in alkaptonuria were compared. Patients and methods: Sixty-nine patients in each of the nitisinone (10 mg daily) and controls of suitability of nitisinone in alkaptonuria 2 (SONIA 2), as well as 37 and 23 in nitisinone (2 mg daily) and control cohorts at the National Alkaptonuria Centre (NAC), respectively, were followed up for 4 years. Severity of alkaptonuria (AKU) was assessed by the AKU Severity Score Index (AKUSSI). 24-h urine homogentisic acid (uHGA 24 ), serum HGA (sHGA), serum tyrosine (sTYR) and serum nitisinone (sNIT) were also analysed at each time point. Dietetic support was used in the NAC, but not in SONIA 2. Safety outcomes were also compared. All statistical analyses were post hoc. Results:The slope of the AKUSSI was 0.55, 0.19, 0.30, and 0.06 per month in the control NAC, nitisinone NAC, control SONIA 2, and nitisinone SONIA 2 cohorts, respectively. The intersection of the slopes on the x-axis was À132, À411, À295, and À 1460 months, respectively. The control and nitisinone slope comparisons were statistically significant both in the NAC (p < 0.001) and the SONIA 2 (p < 0.001). Corneal keratopathy occurred in 3 and 10 patients in the NAC and SONIA 2, respectively. Discussion: The nitisinone 10 mg dose decreased disease progression more than the 2 mg dose although the incidence of corneal keratopathy was 14.5% and 4.9%, respectively. Conclusion: Nitisinone 10 mg decreased urine and serum HGA, increased serum tyrosine, and decreased disease progression more than 2 mg. Low-protein dietetic support may be needed to mitigate tyrosinaemia following nitisinone.

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Section: Introductionmentioning

confidence: 99%

“…This allows comparison of efficacy and safety data from these two data sets. The objective of this manuscript is to compare the efficacy and specific aspects of safety of nitisinone 2 mg daily with 10 mg daily, in order to guide nitisinone dosing in AKU, an issue also raised in a recently published communication 16 …”

Section: Introductionmentioning

confidence: 99%

Comparing nitisinone 2 mg and 10 mg in the treatment of alkaptonuria—An approach using statistical modelling

et al. 2021

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“…One study has shown that a strict low-protein diet can reduce the production of HGA, thus achieving the purpose of delaying the development of the disease (11). Additionally, a three-year prospective study of 39 patients has confirmed that the use of nitisinone can inhibit the activity of hydroxyphenylalanine oxidase during the formation of HGA, thereby delaying the clinical course of AKU (12). When patients suffer from joint pain, especially knee pain, studies have reported that the use of glucosamine can effectively relieve joint pain (13), but due to the lack of a large number of clinical studies, its clinical effects should be considered with caution.…”

Section: Discussionmentioning

confidence: 99%

Total knee arthroplasty and physical therapy for arthropathy in alkaptonuria: A 4-year follow-up case report

Wu¹,

2023

Front. Surg.

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IntroductionAlkaptonuria is a rare autosomal recessive metabolic disorder which leads to accumulation of homogentisic acid in the body.Case PresentationWe report a rare case of an alkaptonuria-related knee arthritis who underwent left total knee arthroplasty and received postoperative systematic physical therapy in a 57-year-old male patient. The patient has suffered from bilateral knee pain for over 4 years. The patient developed melanin pigmentation on the skin of the whole body, especially on the face and auricle. He self-reported that fresh urine was normal color but after standing overnight, the color deepened to black or soy color. He underwent routine urine examination for many times, but no obvious abnormality was found. The patient has suffered from low back pain for more than 20 years. He had been considered for lumbar disc herniation and ankylosing spondylitis after many in-hospital visits. After symptomatic medication, there was no obvious relief. We followed the patient for 4 years after surgery.ResultThe patient presented with pain relief and enhanced range of motion at the 4-year follow-up. The improvements of daily living and the pain relief suggest that the surgery is appropriate for this rare disease.ConclusionIt is rare that the knee pain is diagnosed as alkaptonuria. After total knee arthroplasty and physical therapy, the patient had a good outcome. This case provides experience for the diagnosis and treatment of alkaptonuria-related knee arthritis.

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“…Important questions such as the optimal age at start of treatment, the desired dose of nitisinone and the need of a diet need to be addressed in our conversations with patients [ 13 ]. When started early in the course of the disease, for instance in the third decade or even earlier, treatment with nitisinone—perhaps at even lower doses than used in the intervention studies—may be able to prevent the development of the long-term consequences as a result of its HGA-reducing properties.…”

Section: Preventive Treatment With Low-dose Nitisinonementioning

confidence: 99%

Preventive use of nitisinone in alkaptonuria

Wolffenbuttel

Heiner‐Fokkema

Spronsen

2021

Orphanet J Rare Dis

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Alkaptonuria (AKU, OMIM 203500) is a rare congenital disorder caused by a deficiency of the enzyme homogentisate-1,2,-dioxygenase. The long-term consequences of AKU are joint problems, cardiac valve abnormalities and renal problems. Landmark intervention studies with nitisinone 10 mg daily, suppressing an upstream enzyme activity, demonstrated its beneficial effects in AKU patients with established complications, which usually start to develop in the fourth decade. Lower dose of nitisinone in the range of 0.2–2 mg daily will already reduce urinary homogentisic acid (uHGA) excretion by > 90%, which may prevent AKU-related complications earlier in the course of the disease while limiting the possibility of side-effects related to the increase of plasma tyrosine levels caused by nitisinone. Future preventive studies should establish the lowest possible dose for an individual patient, the best age to start treatment and also collect evidence to which level uHGA excretion should be reduced to prevent complications.

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Suitability of nitisinone for alkaptonuria

Cited by 7 publications

References 8 publications

Comparing nitisinone 2 mg and 10 mg in the treatment of alkaptonuria—An approach using statistical modelling

Comparing nitisinone 2 mg and 10 mg in the treatment of alkaptonuria—An approach using statistical modelling

Total knee arthroplasty and physical therapy for arthropathy in alkaptonuria: A 4-year follow-up case report

Preventive use of nitisinone in alkaptonuria

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