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Asian Biomedicine : Research, Reviews... Jun 2021Alkaptonuria is a rare genetic metabolic disorder due to deficiency of homogentisate 1,2-dioxygenase (HGD), an enzyme catalyzing the conversion of homogentisate to...
BACKGROUND
Alkaptonuria is a rare genetic metabolic disorder due to deficiency of homogentisate 1,2-dioxygenase (HGD), an enzyme catalyzing the conversion of homogentisate to 4-maleylacetoacetate in the pathway for the catabolism of phenylalanine and tyrosine. HGD deficiency results in accumulation of homogentisic acid and its pigmented polymer. Ochronosis is a bluish-black discoloration due to the deposition of the polymer in collagenous tissues. Extensive ochronotic involvement of the Achilles tendon in alkaptonuria and its surgical treatment is rarely reported.
CASE REPORT
A 43-year-old man presented to our clinic in March 2019 with sudden onset of left Achilles tendon pain with no history of prior trauma. Surgical exploration revealed a complete disruption of the tendon at its attachment to the calcaneus. Black pigmentation was extensive and reached the calcaneal tuberosity, extending about 7 cm from the insertion.
DISCUSSION
Achilles reconstruction was performed using flexor hallucis longus tendon transfer. The patient experienced uncomplicated healing with satisfactory functional results.
CONCLUSION
Orthopedic surgeons should be aware of the progressive nature of alkaptonuria. Extensive degenerative changes of the ruptured tendon should be suspected so that physicians can plan tendon repair and facilitate prompt surgical intervention.
PubMed: 37551372
DOI: 10.2478/abm-2021-0016 -
Case Reports in Dermatological Medicine 2023The cosmetic use of skin bleaching products is common among women in sub-Saharan Africa despite numerous reported cutaneous and systemic complications. We report the...
BACKGROUND
The cosmetic use of skin bleaching products is common among women in sub-Saharan Africa despite numerous reported cutaneous and systemic complications. We report the first case of squamous cell carcinoma in a woman using skin bleaching products in Togo. . A 65-year-old woman with a 30-year history of skin bleaching products use consulted in dermatology for a tumor of the neck that had been evolving for 2 years. There was no personal or family history of cancer. The patient was obese (BMI = 38.3 kg/m) and had high blood pressure. Clinical examination noted multiple ulcerative and cauliflower tumors of the neck. The presence of stretch marks, skin atrophy, and ochronosis was noted in the examination of the rest of skin. There were no lymph nodes. HIV serology was negative. Histology of a tumor biopsy concluded to an invasive skin squamous cell carcinoma. The cervical, thoracic, abdominal, and pelvic TDM revealed pulmonary metastases. The patient underwent complete surgical removal of the right latero-cervical tumor. The left latero-cervical tumors were not removed because they infiltrated the large vessels. Chemotherapy before surgery was prescribed but not honored for financial reasons. The patient died 2 months after her first consultation in respiratory distress.
CONCLUSION
Squamous cell carcinoma is one of the complications of skin bleaching in sub-Saharan Africa. It is necessary to intensify awareness campaigns on the complications of this practice, in order to reduce their incidence, in our context where this practice is very frequent.
PubMed: 36684806
DOI: 10.1155/2023/8002896 -
Journal of Inherited Metabolic Disease Nov 2021
Topics: Alkaptonuria; Arthroplasty, Replacement, Knee; Cartilage; Homogentisic Acid; Humans; Incidental Findings; Joint Diseases; Male; Middle Aged; Ochronosis
PubMed: 34264534
DOI: 10.1002/jimd.12417 -
Journal of Cutaneous and Aesthetic... 2024Facial pigmentation is a common presentation of patients attending dermatology out patient department (OPD) and is of great concern to patients. Facial pigmentation may...
INTRODUCTION
Facial pigmentation is a common presentation of patients attending dermatology out patient department (OPD) and is of great concern to patients. Facial pigmentation may be multifactorial and is only rarely diagnosed accurately by a detailed history and clinical examination. Pigmentary disorders cause psychological distress and negatively impact the quality of life of an individual.
AIMS AND OBJECTIVES
(1) To study different dermoscopic patterns in facial melanosis. (2) To estimate the frequency of different dermoscopic patterns.
MATERIALS AND METHODS
Patients with facial hyperpigmentation attending the dermatology OPD were recruited after taking their written consent. A detailed history was taken to collect demographic data. Clinical examination and dermoscopy were done in all patients. Biopsy was done as and when required. Descriptive statistics has been used to describe the quantitative data. Qualitative data were presented as frequency and percentage for clinical and dermoscopic patterns.
RESULTS
The study included 100 patients with 15 different facial melanoses. The most common age group affected was 21-40 years in 53 (53%) cases. The female-to-male ratio was 1.63:1. Melasma was reported as the most common cause of facial melanosis constituting 49 (49%) of the total cases. Out of the total melasma cases, epidermal melasma constituted 22 (45%) cases, dermal melasma constituted four (4%) cases and mixed melasma constituted 23 (47%) cases. Other cases included were lichen planus pigmentosus (14; 14%), facial acanthosis nigricans (14; 14%), periorbital hyperpigmentation (7; 7%), post-inflammatory hyperpigmentation (4; 4%), exogenous ochronosis (2; 2%), lentigines (2; 2%), frictional melanosis (2;2%), and one case each of Becker's nevus, nevus of Ota, olanzapine-induced hyperpigmentation, Riehl's melanosis, macular amyloidosis, and tanning.
CONCLUSIONS
Melasma was reported as the most common cause of facial melanosis. The most common dermoscopic feature was accentuated pseudopigment network. The study is beneficial in understanding the different clinical and dermoscopic patterns of facial melanosis, thus helping the physician to effectively manage the conditions and reduce the need of biopsy.
LIMITATIONS
(1) A small sample size. (2) Histopathological correlation was not done in all cases.
PubMed: 38800811
DOI: 10.4103/JCAS.JCAS_48_23 -
Cureus Mar 2023Alkaptonuria is a rare genetic metabolic disorder of autosomal recessive inheritance characterised by the accumulation of homogentisic acid in the body. It is diagnosed...
Alkaptonuria is a rare genetic metabolic disorder of autosomal recessive inheritance characterised by the accumulation of homogentisic acid in the body. It is diagnosed upon identification of characteristic symptoms, using various biochemical investigations, radiographic pictures, and a variety of specialised tests. Here we are discussing the case of an 80-year-old female patient with incidental findings of alkaptonuria. It is crucial to understand the fundamental diagnostic investigations that can be used in low-income nations or facilities where investigations like genetic testing, gas chromatography, and mass spectrometry are not readily available for the diagnosis of alkaptonuria.
PubMed: 37025736
DOI: 10.7759/cureus.35792 -
Acta Ortopedica Mexicana 2022alkaptonuria is a very rare metabolic disease with autosomal recessive inheritance due to HGA oxidase deficiency. Classically described and diagnosed in the third to...
INTRODUCTION
alkaptonuria is a very rare metabolic disease with autosomal recessive inheritance due to HGA oxidase deficiency. Classically described and diagnosed in the third to fourth decade of life, affecting both men and women; Its diagnostic impression is clinical based on the blue/black coloration of the conjunctivae, however it is confirmed by the specific analysis of the enzyme in the urine, to date there is no cure and its treatment is palliative and symptomatic.
MATERIAL AND METHODS
descriptive, observational, case series study, the primary objective of which is to describe the progression of the disease and its involvement in the musculoskeletal system.
RESULTS
two clinical cases are presented in women and men in which the broad clinic is illustrated, its progressive advance and the different alterations that it can generate in the musculoskeletal system.
CONCLUSIONS
alkaptonuria is a rare disease which leads to a severe secondary arthropathy, currently without a specific management which is based on treating the symptoms, in its final stages joint replacements are a management option with satisfactory results for the relief of pain.
Topics: Male; Humans; Female; Alkaptonuria; Ochronosis; Arthroplasty, Replacement; Joint Diseases; Osteoarthritis; Cartilage Diseases
PubMed: 37669658
DOI: No ID Found -
Human Molecular Genetics Dec 2019Alkaptonuria is an inherited disease caused by homogentisate 1,2-dioxygenase (HGD) deficiency. Circulating homogentisic acid (HGA) is elevated and deposits in connective...
Conditional targeting in mice reveals that hepatic homogentisate 1,2-dioxygenase activity is essential in reducing circulating homogentisic acid and for effective therapy in the genetic disease alkaptonuria.
Alkaptonuria is an inherited disease caused by homogentisate 1,2-dioxygenase (HGD) deficiency. Circulating homogentisic acid (HGA) is elevated and deposits in connective tissues as ochronotic pigment. In this study, we aimed to define developmental and adult HGD tissue expression and determine the location and amount of gene activity required to lower circulating HGA and rescue the alkaptonuria phenotype. We generated an alkaptonuria mouse model using a knockout-first design for the disruption of the HGD gene. Hgd tm1a -/- mice showed elevated HGA and ochronosis in adulthood. LacZ staining driven by the endogenous HGD promoter was localised to only liver parenchymal cells and kidney proximal tubules in adulthood, commencing at E12.5 and E15.5 respectively. Following removal of the gene trap cassette to obtain a normal mouse with a floxed 6th HGD exon, a double transgenic was then created with Mx1-Cre which conditionally deleted HGD in liver in a dose dependent manner. 20% of HGD mRNA remaining in liver did not rescue the disease, suggesting that we need more than 20% of liver HGD to correct the disease in gene therapy. Kidney HGD activity which remained intact reduced urinary HGA, most likely by increased absorption, but did not reduce plasma HGA nor did it prevent ochronosis. In addition, downstream metabolites of exogenous 13C6-HGA, were detected in heterozygous plasma, revealing that hepatocytes take up and metabolise HGA. This novel alkaptonuria mouse model demonstrated the importance of targeting liver for therapeutic intervention, supported by our observation that hepatocytes take up and metabolise HGA.
Topics: Alkaptonuria; Animals; Disease Models, Animal; Gene Knockout Techniques; Homogentisate 1,2-Dioxygenase; Homogentisic Acid; Liver; Male; Mice; Mice, Transgenic; Promoter Regions, Genetic
PubMed: 31600782
DOI: 10.1093/hmg/ddz234 -
Arthroplasty (London, England) Oct 2019The objective of this study is to share our experience in total hip replacement for the treatment of ochronotic hip arthritis, in particular to report how to establish...
BACKGROUND
The objective of this study is to share our experience in total hip replacement for the treatment of ochronotic hip arthritis, in particular to report how to establish the diagnosis and some tips to limit complications.
METHOD
A cohort comprised of 10 patients (12 hips) with alkaptonuric hip arthritis. There were six men and four women with the mean age of 62.80 ± 7.57 years. All patients had a stiff spine, grossly restricted movements of hip joints, and severely limited daily routine activities. Total hip replacement was performed in all patients. The patients were evaluated at 6, 12, and 24 months after surgery, as well as every 4 years thereafter. Harris hip score was used to assess the functional outcome. The level of significance was set at p < 0.05.
RESULTS
The mean follow-up lasted 16.70 ± 6.82 years (3 to 24 years). At the final available follow-up, nine patients returned to work, ambulate without an orthosis, and achieve complete pain relief. Harris hip score was improved from poor to excellent. One patient died 16 years after surgery due to breast cancer. No complication relating to prosthetic failures was detected.
CONCLUSION
Total hip replacement gives long-term satisfactory results in patients with alkaptonuric hip arthritis, resulting in comparable function of the hips in patients who undergo primary osteoarthrosis.
PubMed: 35240771
DOI: 10.1186/s42836-019-0010-8 -
Joint replacement risk is markedly increased in alkaptonuria (AKU) in those with prior arthroplasty.Molecular Genetics and Metabolism... Sep 2024Increased homogentisic acid (HGA) in alkaptonuria (AKU) causes severe arthritis. Nitisinone reduces the production of HGA, but whether it also decreases arthroplasty was...
BACKGROUND
Increased homogentisic acid (HGA) in alkaptonuria (AKU) causes severe arthritis. Nitisinone reduces the production of HGA, but whether it also decreases arthroplasty was examined in 237 AKU patients.
PATIENTS AND METHODS
Patients attending the United Kingdom National Alkaptonuria Centre (NAC) and the Suitability of Nitisinone in Alkaptonuria 2 (SONIA 2) study were studied. Assessments included questionnaires eliciting details of arthroplasty. Nitisinone was administered from baseline, 2 mg in the NAC and 10 mg in SONIA 2. In SONIA 2, subgroups consisted of those with baseline arthroplasty on and not on nitisinone (BR + N+, BR + N-), as well as those without baseline arthroplasty on and not on nitisinone (BR-N+, BR-N-).
RESULTS
In the SONIA2 subgroups, new joint replacement (JR) probabilities after baseline were significantly different (BR + N+, BR + N-, BR-N+, BR-N-) (χ = 23.3, < 0.001); mean (SD) was 3.8 (0.1) years in BR-N-, 3.7 (0.1) years in BR-N+, 3.4 (0.3) years in BR + N-, and 3.0 (0.3) years in BR + N+. Further, the BR + N- showed more JR than the BR-N- subgroup ( < 0.01), while BR + N+ similarly showed more JR than the BR-N+ subgroup ( < 0.001).In the NAC, the BR- group had a mean age of 51.6 7.0) years at baseline but 57.7 (8.7) years at final follow up during nitisinone therapy and showed only 7 incident JR. The BR+ group had an age at baseline of 57.4 (8.5) years and had undergone 94 JRs at baseline.
CONCLUSION
The incidence of arthroplasty was earlier and more frequent after the first JR and was not affected by nitisinone.
PubMed: 38846518
DOI: 10.1016/j.ymgmr.2024.101097 -
Anais Brasileiros de Dermatologia 2023
Topics: Humans; Carbon Dioxide; Ochronosis; Alkaptonuria; Lasers, Gas; Treatment Outcome
PubMed: 36273949
DOI: 10.1016/j.abd.2021.08.013