Dataset Information

Fatal acute haemolysis and methaemoglobinaemia in a man with renal failure and Alkaptonuria - Is nitisinone the solution?

ABSTRACT: Haemolysis and methaemoglobinaemia (MetHb) are rare metabolic complications that can occur in Alkaptonuria (AKU), for which there is no curative treatment. Presented is a case of a man who had AKU, and serves as a reminder of life-threatening complications that can occur with haemolysis and MetHb. This case presents an opportunity to revisit important considerations relating to the investigation and treatment of haemolysis and MetHb with a view to raising awareness, and in doing so hopefully reducing the uniformly fatal outcome. Additionally it is proposed that treatment of haemolysis and MetHb with nitisinone is considered as a potentially lifesaving treatment as it is believed that reducing the concentration of circulating homogentisic acid will reduce oxidative stress.

SUBMITTER: Davison AS

PROVIDER: S-EPMC7171525 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Fatal acute haemolysis and methaemoglobinaemia in a man with renal failure and Alkaptonuria - Is nitisinone the solution?

Davison A S AS Luangrath E E Selvi E E Ranganath L R LR

Molecular genetics and metabolism reports 20200416

Haemolysis and methaemoglobinaemia (MetHb) are rare metabolic complications that can occur in Alkaptonuria (AKU), for which there is no curative treatment. Presented is a case of a man who had AKU, and serves as a reminder of life-threatening complications that can occur with haemolysis and MetHb. This case presents an opportunity to revisit important considerations relating to the investigation and treatment of haemolysis and MetHb with a view to raising awareness, and in doing so hopefully red ...[more]

PMID: 32322505

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Project description:Alkaptonuria (AKU) is caused by homogentisate 1,2-dioxygenase deficiency that leads to homogentisic acid (HGA) accumulation, ochronosis and severe osteoarthropathy. Recently, nitisinone treatment, which blocks HGA formation, has been effective in AKU patients. However, a consequence of nitisinone is elevated tyrosine that can cause keratopathy. The effect of tyrosine and phenylalanine dietary restriction was investigated in nitisinone-treated AKU mice, and in an observational study of dietary intervention in AKU patients. Nitisinone-treated AKU mice were fed tyrosine/phenylalanine-free and phenylalanine-free diets with phenylalanine supplementation in drinking water. Tyrosine metabolites were measured pre-nitisinone, post-nitisinone, and after dietary restriction. Subsequently an observational study was undertaken in 10 patients attending the National Alkaptonuria Centre (NAC), with tyrosine >700??mol/L who had been advised to restrict dietary protein intake and where necessary, to use tyrosine/phenylalanine-free amino acid supplements. Elevated tyrosine (813??mol/L) was significantly reduced in nitisinone-treated AKU mice fed a tyrosine/phenylalanine-free diet in a dose responsive manner. At 3?days of restriction, tyrosine was 389.3, 274.8, and 144.3 ?mol/L with decreasing phenylalanine doses. In contrast, tyrosine was not effectively reduced in mice by a phenylalanine-free diet; at 3?days tyrosine was 757.3, 530.2, and 656.2 ?mol/L, with no dose response to phenylalanine supplementation. In NAC patients, tyrosine was significantly reduced (P =?.002) when restricting dietary protein alone, and when combined with tyrosine/phenylalanine-free amino acid supplementation; 4 out of 10 patients achieved tyrosine <700??mol/L. Tyrosine/phenylalanine dietary restriction significantly reduced nitisinone-induced tyrosinemia in mice, with phenylalanine restriction alone proving ineffective. Similarly, protein restriction significantly reduced circulating tyrosine in AKU patients.

Dataset Information

Fatal acute haemolysis and methaemoglobinaemia in a man with renal failure and Alkaptonuria - Is nitisinone the solution?

Publications

Fatal acute haemolysis and methaemoglobinaemia in a man with renal failure and Alkaptonuria - Is nitisinone the solution?

Similar Datasets

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