Abstract
BackgroundAlkaptonuria (AKU) is an inborn error of catabolism due to a deficient activity of homogentisate 1,2-dioxygenase. Patients suffer from a severe arthropathy, cardiovascular and kidney disease but other organs are affected, too. We found secondary amyloidosis as a life-threatening complication in AKU, thus opening new perspectives for its treatment. We proved that methotrexate and anti-oxidants have an excellent efficacy to inhibit the production of amyloid in AKU model chondrocytes. Owing to the progressive and intractable condition, it seems important to detect amyloid deposits at an early phase in AKU and the choice of specimens for a correct diagnosis is crucial.MethodsTen AKU subjects were examined for amyloidosis; abdominal fat pad aspirates, labial salivary gland, cartilage and synovia specimens were analysed by CR, Th-T, IF, TEM.ResultsAmyloid was detected in only one abdominal fat pad specimen. However, all subjects demonstrated amyloid deposition in salivary glands and in other organ biopsies, indicating salivary gland as the ideal specimen for early amyloid detection in AKU.ConclusionsThis is, at the best of our knowledge, the first report providing correct indications on the diagnosis of amyloidosis in AKU, thus offering the possibility of treatment of such co-morbidity to AKU patients.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_185
Highlights
Alkaptonuria (AKU) is an inborn error of catabolism due to a deficient activity of homogentisate 1,2-dioxygenase
Secondary (AA) amyloidosis is caused by a chronic infection or chronic inflammatory disease where deposits are made up of serum amyloid A (SAA) produced during inflammation
We found SAA amyloidosis as a life-threatening complication in alkaptonuria (AKU) [1], an ultra-rare (1:250.0001.000.000 incidence) autosomal recessive genetic disease due to a deficient activity of homogentisate 1,2-dioxygenase (HGD) leading to the accumulation of homogentisic acid (HGA)
Summary
Alkaptonuria (AKU) is an inborn error of catabolism due to a deficient activity of homogentisate 1,2-dioxygenase. We found SAA amyloidosis as a life-threatening complication in alkaptonuria (AKU) [1], an ultra-rare (1:250.0001.000.000 incidence) autosomal recessive genetic disease due to a deficient activity of homogentisate 1,2-dioxygenase (HGD) leading to the accumulation of homogentisic acid (HGA). HGA-oxidized derivative benzoquinone acetic acid (BQA) forms deposits in the connective tissue, causing a pigmentation known as “ochronosis”, leading to dramatic organ damage. A severe form of arthropathy is AA amyloidosis is one of the most severe complications of several chronic rheumatic disorders [2,3] and is a secondary complication of AKU due to a chronic inflammatory status derived from HGA/BQA-induced oxidative stress [4,5,6,7,8,9,10,11,12]. SAA-amyloid in AKU co-localizes with ochronotic pigment [1], AKU is a complicated inflammatory multisystemic disease, and any body district expressing HGD may be affected [13]
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