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

Alkaptonuria is a rare genetic disorder characterized by a high level of circulating (and urine) homogentisic acid (HGA), which contributes to ochronosis when it is deposited in connective tissue as a pigmented polymer. In an observational study carried out by National AKU Centre (NAC) in Liverpool, a total of thirty-nine AKU patients attended yearly visits in varying numbers. At each visit a mixture of clinical, joint and spinal assessments were carried out and the results calculated to yield an AKUSSI (Alkaptonuria Severity Score Index), see "Nitisinone arrests ochronosis and decreases rate of progression of Alkaptonuria: evaluation of the effect of nitisinone in the United Kingdom National Alkaptonuria Centre" (Ranganath at el., 2018). The aim of this data article is to produce visual representation of the change in the components of AKUSSI over 3 years, through radar charts. The metabolic effect of nitisinone is shown through box plots.

Nitisinone arrests ochronosis and decreases rate of progression of Alkaptonuria: Evaluation of the effect of nitisinone in the United Kingdom National Alkaptonuria Centre.

QUESTION: Does Nitisinone prevent the clinical progression of the Alkaptonuria? FINDINGS: In this observational study on 39 patients, 2 mg of daily nitisinone inhibited ochronosis and significantly slowed the progression of AKU over a three-year period. MEANING: Nitisinone is a beneficial therapy in Alkaptonuria. BACKGROUND: Nitisinone decreases homogentisic acid (HGA), but has not been shown to modify progression of Alkaptonuria (AKU). METHODS: Thirty-nine AKU patients attended the National AKU Centre (NAC) in Liverpool for assessments and treatment. Nitisinone was commenced at V1 or baseline. Thirty nine, 34 and 22 AKU patients completed 1, 2 and 3 years of monitoring respectively (V2, V3 and V4) in the VAR group. Seventeen patients also attended a pre-baseline visit (V0) in the VAR group. Within the 39 patients, a subgroup of the same ten patients attended V0, V1, V2, V3 and V4 visits constituting the SAME Group. Severity of AKU was assessed by calculation of the AKU Severity Score Index (AKUSSI) allowing comparison between the pre-nitisinone and the nitisinone treatment phases. RESULTS: The ALL (sum of clinical, joint and spine AKUSSI features) AKUSSI rate of change of scores/patient/month, in the SAME group, was significantly lower at two (0.32 ±â€¯0.19) and three (0.15 ±â€¯0.13) years post-nitisinone when compared to pre-nitisinone (0.65 ±â€¯0.15) (p < .01 for both comparisons). Similarly, the ALL AKUSSI rate of change of scores/patient/month, in the VAR group, was significantly lower at one (0.16 ±â€¯0.08) and three (0.19 ±â€¯0.06) years post-nitisinone when compared to pre-nitisinone (0.59 ±â€¯0.13) (p < .01 for both comparisons). Combined ear and ocular ochronosis rate of change of scores/patient/month was significantly lower at one, two and three year's post-nitisinone in both VAR and SAME groups compared with pre-nitisinone (p < .05). CONCLUSION: This is the first indication that a 2 mg dose of nitisinone slows down the clinical progression of AKU. Combined ocular and ear ochronosis progression was arrested by nitisinone.

Bone turnover in untreated polymyalgia rheumatica.

BACKGROUND: Polymyalgia rheumatica (PMR) is a common condition in the elderly. A previous study demonstrated that it is associated with an increase in bone resorption. This effect was ameliorated by steroids, implying that inflammation is the cause of increased bone resorption and that this can be reduced by steroids. This is in keeping with accumulating evidence that systemic inflammation is associated with bone resorption and bone loss. We studied bone formation and resorption markers in 53 patients with PMR prior to any therapeutic intervention. METHODS: Bone resorption was measured by estimating urinary free pyridinoline (fPYD) and deoxypyridinoline (fDPD). Bone formation was estimated by measuring serum concentrations of procollagen type 1 N-terminal propeptide (P1NP). Disease activity was assessed using inflammatory markers (erythrocyte sedimentation rate and C-reactive protein). Patients had a baseline dual-energy X-ray absorptiometer scan to assess bone mineral density. RESULTS: Bone resorption markers were significantly increased and bone formation markers significantly decreased in PMR patients prior to treatment, compared with a control population matched for gender and age. CONCLUSIONS: This implies that bone turnover is uncoupled in PMR. This may lead to a decrease in skeletal mass in the long term due to the disease process alone. However, no significant loss of bone mineral density was detected. It is possible that, due to the acute onset of PMR, increased bone resorption is not present long enough to result in a detectable decrease in bone mineral density. The effects of steroid treatment on bone metabolism and the subsequent long-term outcome need to be investigated.

Severe hypercalcaemia in B-cell lymphoma: combined effects of PTH-rP, IL-6 and TNF.

Hypercalcaemia as the only manifestation of B-cell lymphoma is seen very rarely. Its pathophysiology is heterogenous and not well understood. We report a 73-year-old man who presented with severe hypercalcaemia before any signs of malignancy became evident. He was diagnosed with a B-cell lymphoma on bone marrow trephine biopsy. The hypercalcaemia was associated with high plasma concentrations of parathyroid-hormone-related protein, interleukin-6 and tumour necrosis factor. Our patient had markedly increased osteoclast and osteoblast activity as a result of synergistic effects between these factors, with consequent severe hypercalcaemia. This is the first reported example of such combined effects of these factors in humans.