ascorbic-acid and Ochronosis

Alkaptonuria is a disease often forgotten because of its rarity. Its pathogenic mechanism is the deficiency of one of the enzymes of the tyrosine degradation pathway-homogentisate-1, 2-dioxygenase, which sequelae is accumulation and deposition of its metabolite homogentisic acid in connective tissues and urine. Alkaptonuria presents as a clinical triad-darkening urine upon prolonged exposure to air, pigmentation of connective tissues and debilitating arthropathy. We present a case report of a 67-year old patient with alkaptonuria who presented with the clinical triad, but was mistakenly diagnosed as having ankylosing spondylitis in the past. Currently there is no treatment for the disease hence the management strategy was focused on symptoms control with analgesics, physical therapy, dietary modification, vitamin C supplementation, and joint arthroplasty. Alkaptonuria's clinical features are extensively described in the literature and despite the fact that it is a rare disease, due to the similar radiographic changes with spondyloarthropathies, it should be included in the differential diagnosis in young patients presenting with severe joint involvement. Early recognition of the disease is necessary since its natural evolution is joint destruction leading to significant reduction in the quality of life. Alkaptonuria's articular features in the spine and peripheral tissues are well described using the classical imaging techniques. Musculoskeletal ultrasonography shows a characteristic set of findings in the soft tissues, including synovium, cartilage, tendons and entheses.

Topics: Aged; Alkaptonuria; Ascorbic Acid; Cartilage Diseases; Dioxygenases; Homogentisic Acid; Humans; Joint Diseases; Ochronosis; Osteoarthritis; Quality of Life; Spondylarthropathies; Tyrosine

Alkaptonuria is a rare autosomal recessive metabolic disease that leads to the deposition of homogentisic acid. Ochronotic arthropathy is the articular manifestation of alkaptonuria with the most common clinical feature being severe spondyloarthropathy. We present the case of a 58-year-old woman with back pain. Radiographs and magnetic resonance imaging (MRI) revealed characteristic features of ochronotic spondyloarthropathy. The literature regarding management of alkaptonuria is reviewed.

Topics: Alkaptonuria; Antioxidants; Ascorbic Acid; Female; Homogentisate 1,2-Dioxygenase; Homogentisic Acid; Humans; Low Back Pain; Middle Aged; Ochronosis; Spondylarthropathies

A 50-year-old man presented with a complaint of low-back pain and widespread joint pain for the previous 20 years. Conventional radiography revealed wide areas of calcification in the intervertebral discs and degenerative changes in the peripheral joints. A diagnosis of ochronosis was made by the observation of bluish-brown pigmentation in the nose and ears, dark urine colors following alkalization, and high levels of homogentisic acid in the urine. Ochronosis should be considered in the differential diagnosis of patients with chronic low-back pain regarding features of widespread calcification in the intervertebral discs at radiography and bluish-brown pigmentation in the nose and ears.

Topics: Alkaptonuria; Anti-Inflammatory Agents, Non-Steroidal; Arthralgia; Ascorbic Acid; Back Pain; Calcinosis; Chronic Disease; Diagnosis, Differential; Diclofenac; Homogentisic Acid; Humans; Intervertebral Disc; Male; Middle Aged; Ochronosis; Radiography; Treatment Outcome; Vitamins

Topics: Alkaptonuria; Ascorbic Acid; Cartilage, Articular; Homogentisic Acid; Humans; Joint Diseases; Ochronosis; Oxygenases; Tyrosine

Alkaptonuria is a rare genetic disorder resulting in abnormality of tyrosine metabolism. It is one of the Garrod's tetrad of 'inborn errors of metabolism' proposed to have Mendelian recessive inheritance. The disorder is characterised by deposition of homogentisic acid leading to ochronosis and ochronotic osteoarthropathy; however, blackish discoloration of urine is the only childhood manifestation. Other manifestations present only after third decade. A 13-year-old boy presented to paediatric nephrology clinic with blackish discolouration of urine since infancy. Examination revealed bluish black discolouration of bilateral sclera and ear cartilage; however, he had no symptoms of ochronotic osteoarthropathy. Genetic test pointed towards alkaptonuria. Currently, he is on regular follow-up and is being treated with vitamin C to delay the progression of the disease. Early diagnosis with appropriate intervention delays the onset of complications and preserves the quality of life of the patient.

Topics: Adolescent; Alkaptonuria; Antioxidants; Ascorbic Acid; Disease Progression; Early Diagnosis; Humans; Male; Ochronosis; Sclera

Alkaptonuria (AKU) is a rare genetic disease associated with deficient homogentisate 1,2-dioxygenase activity in the liver. This leads to the accumulation of homogentisic acid (HGA) and its oxidized/polymerized products in connective tissues, which in turn become characterized by the presence of melanin-like pigments (ochronosis). Since at present, further studies are necessary to support the use of drugs for the treatment of AKU, we investigated the effects of various anti-oxidants in counteracting melanin-like pigmentation and oxidative stress related to HGA and its metabolites.. We set up an in vitro model using human serum treated with 0.33 mM HGA and tested the anti-oxidants ascorbic acid, N-acetylcysteine, phytic acid (PHY), taurine (TAU), ferulic acid (FER) and lipoic acid (LIP) for their ability to prevent or delay the production of melanin-like pigments, as well as to reduce oxidative post-translational modifications of proteins. Monitoring of intrinsic fluorescence of HGA-induced melanin-like pigments was used to evaluate the efficacy of compounds.. Our model allowed us to prove efficacy especially for PHY, TAU, LIP and FER in counteracting the production of HGA-induced melanin-like pigments and protein oxidation induced by HGA and its metabolites.. Our model allows the opening of new anti-oxidant therapeutic strategies to treat alkaptonuric ochronosis.

Topics: Acetylcysteine; Alkaptonuria; Antioxidants; Ascorbic Acid; Cells, Cultured; Coumaric Acids; Homogentisic Acid; Humans; Ochronosis; Oxidative Stress; Phytic Acid; Protein Carbonylation; Taurine; Thioctic Acid

Alkaptonuria (AKU) is a rare autosomal recessive disease, associated with deficiency of homogentisate 1,2-dioxygenase activity in the liver. This leads to an accumulation of homogentisic acid (HGA) and its oxidized derivatives in polymerized form in connective tissues especially in joints. Currently, AKU lacks an appropriate therapy. Hence, we propose a new treatment for AKU using the antioxidant N-acetylcysteine (NAC) administered in combinations with ascorbic acid (ASC) since it has been proven that NAC counteracts the side-effects of ASC. We established an in vitro cell model using human articular primary chondrocytes challenged with an excess of HGA (0.33 mM). We used this experimental model to undertake pre-clinical testing of potential antioxidative therapies for AKU, evaluating apoptosis, viability, proliferation, and metabolism of chondrocytes exposed to HGA and treated with NAC and ASC administered alone or in combination addition of both. NAC decreased apoptosis induced in chondrocytes by HGA, increased chondrocyte growth reduced by HGA, and partially restored proteoglycan release inhibited by HGA. A significantly improvement in efficacy was found with combined addition of the two antioxidants in comparison with NAC and ASC alone. Our novel in vitro AKU model allowed us to demonstrate the efficacy of the co-administration of NAC and ASC to counteract the negative effects of HGA for the treatment of ochronotic arthropathy.

Topics: Acetylcysteine; Alkaptonuria; Antioxidants; Apoptosis; Ascorbic Acid; Cartilage, Articular; Cell Proliferation; Cell Survival; Cells, Cultured; Chondrocytes; Homogentisate 1,2-Dioxygenase; Homogentisic Acid; Humans; Ochronosis; Protein Carbonylation

A 38 years old man presented with 2 years history of low backache and progressively increasing stiffness of the spine. Movements were restricted at lumbar spine due to stiffness especially forward flexion was markedly reduced. He was suspected to be suffering from ankylosing spondylitis. There was no tenderness over sacroiliac joints or lumbar spine. Yellowish green Ochronotic pigmentation of cartilage of ears was noted. Radiographs of lumbar and thoracic spine revealed narrowing of inter-vertebral spaces with calcification of intervertebral discs. Homogentisic acid was present in the patient's urine sample, suggesting him to be suffering from Alkaptonuria. Patient is being managed with non steroidal anti-inflammatory drugs and vitamin C, 1g daily.

Topics: Adult; Alkaptonuria; Anti-Inflammatory Agents, Non-Steroidal; Ascorbic Acid; Homogentisic Acid; Humans; Intervertebral Disc; Low Back Pain; Male; Ochronosis; Radiography; Spondylitis, Ankylosing; Treatment Outcome; Vitamins

Endogenous ochronosis or alkaptonuria is a rare, autosomal recessive disease of tyrosine metabolism that is caused by a deficiency of the enzyme homogentisic acid oxidase. The disease results in the accumulation and deposition of homogentisic acid in the cartilage, eyelids, forehead, cheeks, axillae, genital region, buccal mucosa, larynx, tympanic membranes, and tendons. The disease generally presents in adults with arthritis and skin abnormalities; occasionally, involvement of other organs may be seen. A 49-year-old man was referred to our clinic with verrucous lesions on his hands. On physical examination, caviar-like ochronotic papules were found around his eyes and the helix cartilage of his ears, and on the dorsa of both hands. There were brown macules on the sclera (Osler's sign). The patient had arthritis and nephrolithiasis, and a sample of his urine darkened upon standing. Histopathological examination showed deposition of ochronotic pigment. High-dose ascorbic acid was given, and the patient showed improvement on follow-up examination 6 months later.

Topics: Ascorbic Acid; Ear, External; Female; Humans; Middle Aged; Ochronosis; Treatment Outcome

Topics: Alkaptonuria; Animals; Ascorbic Acid; Dioxygenases; Homogentisate 1,2-Dioxygenase; Homogentisic Acid; Humans; Liver; Mice; Ochronosis; Oxygenases

Topics: Alkaptonuria; Ascorbic Acid; Diagnosis, Differential; Diet Therapy; Dietary Proteins; Humans; Joint Diseases; Male; Middle Aged; Ochronosis; Radiography

Topics: Ascorbic Acid; Cartilage; Collagen; Cytoplasm; Eye; Histiocytes; Humans; Male; Methenolone; Microscopy, Electron; Muscles; Ochronosis; Physical Therapy Modalities; Radiography; Skin

Topics: Alkaptonuria; Ascorbic Acid; Binding Sites; Carbon Isotopes; Connective Tissue; Disease Models, Animal; Ochronosis; Penicillamine; Phenylacetates; Sternum; Tendons; Tyrosine

Topics: Aged; Alkaptonuria; Ascorbic Acid; Diagnosis, Differential; Female; Femoral Neck Fractures; Humans; Methandrostenolone; Ochronosis; Osteoporosis; Phenylacetates; Polymyalgia Rheumatica; Radiography; Skull; Vitamin D

Topics: Adult; Alkaptonuria; Ascorbic Acid; Bone and Bones; Female; Humans; Methylthiouracil; Ochronosis; Physical Therapy Modalities; Radiography

Topics: Ascorbic Acid; Humans; Methylthiouracil; Ochronosis; Osteoarthritis; Thiouracil; Vitamins