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Sclerouveitis as Part of Multiple Autoimmune Syndrome in a Patient with Alkaptonuria: A Case Report.Ocular Immunology and Inflammation Jul 2024To present a novel association of multiple autoimmune syndrome (MAS) in a patient with sclerouveitis and alkaptonuria.
PURPOSE
To present a novel association of multiple autoimmune syndrome (MAS) in a patient with sclerouveitis and alkaptonuria.
CASE REPORT
A 68-year-old female with alkaptonuria, Hashimoto's thyroiditis, and familial autoimmunity presented with decreased VA, red eye, foreign body sensation, and ocular pain. Ophthalmological examination: OD conjunctival hyperemia, ochronosis, a reddish-violet scleral nodule, keratic precipitates, 2+ cells in the anterior chamber, 0.5+ vitreous cells, and mild vitreous haze. The patient was diagnosed with anterior uveitis and anterior nodular scleritis. Due to the associated sicca symptoms, a salivary gland biopsy was ordered, confirming Sjögren's syndrome. Then, MAS was diagnosed, and immunomodulatory medications were started; however, as she was refractory to more than two of them, it was suggested to start biological treatment.
CONCLUSION
We present a novel MAS-type 2 pattern consisting of Hashimoto's thyroiditis, sclerouveitis, and Sjögren's syndrome. Its diagnosis and management represent a challenge, so a multidisciplinary approach should be provided.
Topics: Humans; Female; Aged; Alkaptonuria; Scleritis; Sjogren's Syndrome; Hashimoto Disease; Autoimmune Diseases
PubMed: 36821816
DOI: 10.1080/09273948.2023.2179498 -
Cureus Jan 2023Ochronosis is a rare metabolic disorder characterized by homogentisic acid deposition in the large joints and spine, resulting in progressive degeneration. We present...
Ochronosis is a rare metabolic disorder characterized by homogentisic acid deposition in the large joints and spine, resulting in progressive degeneration. We present two cases of ochronotic arthritis of the knee subjected to cemented total knee arthroplasty (TKA). These cases were diagnosed intraoperatively and later confirmed with a histopathologic examination. Orthopedic surgeons should be aware of the condition as the intraoperative finding of darkened cartilage might surprise them. After a five-year TKA follow-up, both of our cases showed better mobility and function.
PubMed: 36779093
DOI: 10.7759/cureus.33523 -
World Journal of Clinical Cases Jan 2023Ochronosis, also known as alkaptonuria, is a rare autosomal recessive self-metabolic disease arising from deficiency of homogentisate 1,2 dioxygenase enzyme. It affects...
BACKGROUND
Ochronosis, also known as alkaptonuria, is a rare autosomal recessive self-metabolic disease arising from deficiency of homogentisate 1,2 dioxygenase enzyme. It affects several organs and muscoskeletal structures. We herein report a case of a patient who presented with severe hip arthropathy complicated with late stage ochronosis.
CASE SUMMARY
A 56-year-old male patient was admitted in our department in 2019 with complaints of chronic low backache and left hip pain. After the required investigations were done, lumbar disc herniation and severe hip arthritis were the initial diagnosis. A total left hip arthroplasty was performed. Ochronotic osteoarthritis was only obtained post-surgery as confirmatory diagnosis. He was again admitted mid 2022 with the same complaints on the right hip. Subsequently, he underwent a total right hip arthroplasty. Post-operative recovery and follow-ups were deemed very satisfactory.
CONCLUSION
Ochronosis is an unusual diagnosis for a patient who presents with typical hip arthritis. Thus, unless meticulous history taking and advanced laboratory tests, the diagnosis can easily be missed by surgeons.
PubMed: 36687193
DOI: 10.12998/wjcc.v11.i1.210 -
Frontiers in Surgery 2022Alkaptonuria is a rare autosomal recessive metabolic disorder which leads to accumulation of homogentisic acid in the body.
INTRODUCTION
Alkaptonuria is a rare autosomal recessive metabolic disorder which leads to accumulation of homogentisic acid in the body.
CASE PRESENTATION
We 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.
RESULT
The 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.
CONCLUSION
It 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.
PubMed: 36684325
DOI: 10.3389/fsurg.2022.913120 -
Frontiers in Surgery 2022Alkaptonuria is a rare autosomal genetic disorder with an incidence of about 1 in 1 million per year. Spinal involvement often manifests in the later stages of the...
BACKGROUND
Alkaptonuria is a rare autosomal genetic disorder with an incidence of about 1 in 1 million per year. Spinal involvement often manifests in the later stages of the disease. However, this is the first report of the presentation of thoracolumbar spinal stenosis.
CASE PRESENTATION
We report the case of a 61-year-old female patient with significant thoracolumbar stenosis symptoms. The patient had obvious kyphosis with preoperative lower extremity muscle strength grade 2/5. Symptoms and imaging signs initially suggested ankylosing spondylitis. This patient was classified into motor incomplete injury (ASIA C). However, the patient was found to have melanin deposits on the sclera and skin, and the urine was darkened at rest. CT and MRI both suggested no bone bridge connection between vertebrae, which was the key difference between ankylosing spondylitis and alkaptonuria in imaging. Most importantly, urine specimen testing and intraoperative pathology demonstrated alkaptonuria. The patient underwent spinal decompression and vertebral body fixation. Postoperative recovery was good: the patient had significantly relieved pain and could stand and walk.
CONCLUSION
This case is the first report of thoracolumbar spinal stenosis associated with alkaptonuria involving the spine.
PubMed: 36684124
DOI: 10.3389/fsurg.2022.1040715 -
Revista Portuguesa de Cardiologia :... Feb 2023
Topics: Humans; Transcatheter Aortic Valve Replacement; Alkaptonuria; Aortic Valve; Aortic Valve Stenosis; Treatment Outcome; Heart Valve Prosthesis
PubMed: 36608903
DOI: 10.1016/j.repc.2023.01.002 -
The American Journal of the Medical... Apr 2023The aim of the current study was to determine whether there is an association between alkaptonuria (AKU) and urinary tract infection (UTI) by exploring the bacterial...
BACKGROUND
The aim of the current study was to determine whether there is an association between alkaptonuria (AKU) and urinary tract infection (UTI) by exploring the bacterial quality of the urinary tract, as most of the patients with AKU present with frequent occurrence of urinary tract symptoms such as incomplete emptying of urinary bladder, dysuria and nocturia.
METHODS
Study samples were collected from 22 participants; 9 from patients with AKU, 9 from individuals who were AKU carriers, and 4 people served as control. Confirmation of AKU diagnosis was established by the ferric chloride test and quantitative determination of urinary homogentisic acid (HGA) levels.
RESULTS
In the ferric chloride test, the urine samples of AKU patients showed a characteristic black ring upon addition of few drops of ferric chloride solution. During urinary HGA determination, patients with AKU had increased levels of urinary HGA as compared to carriers and controls. The following 10 bacterial species were isolated from the urinary tract of AKU patients, carriers and controls: Sphingomonas paucimobilis, Escherichia coli, Francisella tularensis, Staphylococcus hominis, Staphylococcus haemolyticus, Leuconostoc mesenteroides, Dermacoccus nishinomiyaensis, Kytococcus sedentarius, Serratia fonticola and Granulicatella adiacens. The presence of S. paucimobilis was found in three male patients, and one female each from the carrier and control groups. Almost all study samples were positive for D. nishinomiyaensis and K. sedentarius. S. fonticola and G. adiacens were found only in AKU carrier females.
CONCLUSIONS
The results deduced that males show symptoms of arthritis early and more severely than females and by this it appears that there is an association between these symptoms and the percentage of bacterial infection in males that requires more accurate diagnosis and treatment to clarify such relationship. In the current study, males (patients, carriers, and controls) were more likely to have bacterial infections than females (64% vs. 36%). The 16 and 2 bacterial isolates, detected in 7 males and 2 females AKU patients, respectively, revealed that male AKU patients had a 2.3-fold greater rate of bacterial infection than female AKU patients. Therefore, further studies are warranted to investigate if there's any relationship between higher incidence of bacterial infections and development of AKU-related clinical symptoms in the male population.
Topics: Humans; Male; Female; Alkaptonuria; Arthritis; Homogentisic Acid; Urinary Tract
PubMed: 36608845
DOI: 10.1016/j.amjms.2022.12.028 -
Orphanet Journal of Rare Diseases Jan 2023Alkaptonuria is a rare inherited disorder for which there was no disease-modifying treatment. In order to develop a successful approved therapy of AKU multiple barriers... (Review)
Review
Alkaptonuria is a rare inherited disorder for which there was no disease-modifying treatment. In order to develop a successful approved therapy of AKU multiple barriers had to be overcome. These included activities before the conduct of the study including deciding on the drug therapy, the dose of the drug to be used, clarify the nature of the disease, develop outcome measures likely to yield a positive outcome, have a strategy to ensure appropriate patient participation through identification, build a consortium of investigators, obtain regulatory approval for proposed investigation plan and secure funding. Significant barriers were overcome during the conduct of the multicentre study to ensure harmonisation. Mechanisms were put in place to recruit and retain patients in the study. Barriers to patient access following completion of the study and regulatory approval were resolved.
Topics: Humans; Alkaptonuria; Rare Diseases; Cyclohexanones; Nitrobenzoates; Homogentisic Acid; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 36600285
DOI: 10.1186/s13023-022-02606-0 -
Clinical Case Reports Dec 2022Management of osteoporosis in patients with alkaptonuria can be challenging. This is the first case report confirming the effectiveness of teriparatide following...
Management of osteoporosis in patients with alkaptonuria can be challenging. This is the first case report confirming the effectiveness of teriparatide following zoledronic acid therapy in treating osteoporosis and preventing fragility fractures in a patient with alkaptonuria.
PubMed: 36583204
DOI: 10.1002/ccr3.6729 -
International Journal of Molecular... Dec 2022Alkaptonuria (AKU) is an ultra-rare metabolic disease caused by the accumulation of homogentisic acid (HGA), an intermediate product of phenylalanine and tyrosine...
Alkaptonuria (AKU) is an ultra-rare metabolic disease caused by the accumulation of homogentisic acid (HGA), an intermediate product of phenylalanine and tyrosine degradation. AKU patients carry variants within the gene coding for homogentisate-1,2-dioxygenase (HGD), which are responsible for reducing the enzyme catalytic activity and the consequent accumulation of HGA and formation of a dark pigment called the ochronotic pigment. In individuals with alkaptonuria, ochronotic pigmentation of connective tissues occurs, leading to inflammation, degeneration, and eventually osteoarthritis. The molecular mechanisms underlying the multisystemic development of the disease severity are still not fully understood and are mostly limited to the metabolic pathway segment involving HGA. In this view, untargeted metabolomics of biofluids in metabolic diseases allows the direct investigation of molecular species involved in pathways alterations and their interplay. Here, we present the untargeted metabolomics study of AKU through the nuclear magnetic resonance of urine from a cohort of Italian patients; the study aims to unravel molecular species and mechanisms underlying the AKU metabolic disorder. Dysregulation of metabolic pathways other than the HGD route and new potential biomarkers beyond homogentisate are suggested, contributing to a more comprehensive molecular signature definition for AKU and the development of future adjuvant treatment.
Topics: Humans; Alkaptonuria; Metabolomics; Homogentisic Acid; Biomarkers; Dioxygenases; Magnetic Resonance Spectroscopy
PubMed: 36555443
DOI: 10.3390/ijms232415805