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Arthroplasty Today Jun 2020Alkaptonuria is a rare metabolic disorder caused by the deficiency of homogentisic acid oxidase enzyme, which is responsible for eliminating homogentisic acid from the...
Alkaptonuria is a rare metabolic disorder caused by the deficiency of homogentisic acid oxidase enzyme, which is responsible for eliminating homogentisic acid from the body through the renal system. Excessive accumulation of homogentisic acid leads to ochronosis and ochronotic arthritis. Owing to the rarity of the disease, long-term functional outcomes of joint replacements of the hips and knees in ochronosis arthropathy are unconfirmed, and only a limited number of case reports are available on this. We present a case of a 45-year-old man with ochronosis and advanced osteoarthritis of both the hips and knees. He underwent bilateral hip and knee replacements as staged procedures. At a follow-up of more than 12 years, the man had full mobility with no loosening of implants.
PubMed: 32577465
DOI: 10.1016/j.artd.2020.01.012 -
Acta Orthopaedica Et Traumatologica... Dec 2021Alkaptonuria-related rapidly destructive arthropathy of the hip joint has not been reported in detail with both imaging and histopathological findings in the literature.... (Review)
Review
Alkaptonuria-related rapidly destructive arthropathy of the hip joint has not been reported in detail with both imaging and histopathological findings in the literature. We, herein, presented the case of a 79-year-old male patient who suddenly started experiencing marked right hip pain. Radiography showed that the femoral head was spherical; however, after 3 months, approximately half of the femoral head was destroyed despite there being almost no change in the acetabulum. Radiographs of the spine also showed fusion between multiple vertebrae. Significant osteoporosis was observed on roentgenography, together with decreased bone density. Urinary gas chromatography-mass spectrometry analysis revealed that a large amount of homogentisic acid was excreted. During total hip arthroplasty, gray and muddy contents were observed in the joint capsule, and the surface of the destroyed femoral head was black. Histopathologically, granulomatous foci containing fragmented bone and cartilage debris were found in the bone marrow space of the joint surface, and the cartilage tissue was pigmented brownish black. The patient was subsequently diagnosed with ochronotic hip joint destruction. The present case report is the first to demonstrate rapidly destructive coxopathy associated with alkaptonuria using both imaging and histopathological findings. These findings clearly show that severe hip joint destruction defined as rapidly destructive hip arthropathy can occur in a very short time period for patients with alkaptonuria.
Topics: Aged; Alkaptonuria; Femur Head; Hip Joint; Humans; Joint Diseases; Male; Ochronosis
PubMed: 34967747
DOI: 10.5152/j.aott.2021.21205 -
Journal of Orthopaedic Case Reports Dec 2021Ochronotic arthropathy (OcA) is a consequence of alkaptonuria, a rare systemic-inherited metabolic disorder leading to accumulation of homogentisic acid in articular...
INTRODUCTION
Ochronotic arthropathy (OcA) is a consequence of alkaptonuria, a rare systemic-inherited metabolic disorder leading to accumulation of homogentisic acid in articular cartilage and subsequent early degeneration of the joints. Only few cases of OcA managed with bilateral total knee arthroplasty (TKA) has been described in the literature so far. We aim to discuss surgical pearls, pitfalls, and clinical outcome of OcA of knees managed with simultaneous bilateral TKA.
CASE PRESENTATION
The patient was a 52-year-old female presented to outpatient facility with severe bilateral knee pain and difficult ambulation. After clinical and radiological diagnosis of osteoarthritis, she was posted for bilateral TKA. During arthrotomy, blackening of articular cartilage, quadriceps and patellar tendon, and synovium was noted. Subchondral bone was free of pigmentation though, seemed osteopenic while taking bone cuts. Right knee was implanted with cruciate retaining components with ultracongruent insert; while on the left side, posterior stabilized components were used. Diagnosis of ochronosis was made retrospectively with characteristic subtle pigmentation of nails, palms, pinnae, and urine homogentisic levels. Two years follow-up of the patient remained satisfactory without any major complications.
CONCLUSION
OcA may present with intra-operative surprise to the surgeon if not anticipated preoperatively. Simultaneous bilateral TKA is safe and effective treatment for end-stage arthritis. However, it is difficult to diagnose it preoperatively; a high clinical suspicion leads to meticulous assessment and counseling regarding potential anesthetic concerns, choice of implant, and possible intra-operative and post-operative complications reported sporadically though.
PubMed: 35415137
DOI: 10.13107/jocr.2021.v11.i12.2554 -
BMJ Case Reports Dec 2021Alkaptonuria (AKU) is a rare autosomal recessive disorder with a global incidence of 1 in 250 000 to 1 million people worldwide. It results from a deficiency of the...
Alkaptonuria (AKU) is a rare autosomal recessive disorder with a global incidence of 1 in 250 000 to 1 million people worldwide. It results from a deficiency of the enzyme homogentisic acid (HGA) oxidase which when absent, leads to an accumulation of HGA. Without this enzymatic degradation, HGA deposits in connective tissues resulting in pigmentation (ochronosis), plaque formation and accelerated cartilage destruction. With this, many patients who suffer from AKU develop ochronotic arthropathies, tendon ruptures, fractures, and chronic joint pain. Similarly, patients can develop cardiac valvular dysfunction and interstitial renal disease. Our two cases highlight the array of pathologies seen in AKU and, in light of newly published research, give us a platform from which we can discuss the developments in management of this rare disease.
Topics: Alkaptonuria; Cartilage, Articular; Homogentisic Acid; Humans; Ochronosis; Rare Diseases
PubMed: 34876442
DOI: 10.1136/bcr-2021-244240 -
International Journal of Surgery Case... 2020Alkaptunurea is a rare metabolic disorder with autosomal recessive genetic pattern in transmission, it is characterized by accumulation of hemogenistic acid in the...
INTRODUCTION
Alkaptunurea is a rare metabolic disorder with autosomal recessive genetic pattern in transmission, it is characterized by accumulation of hemogenistic acid in the tissues due to deficiency of homogentisate 1,2 dioxygenase activity. Characteristically, affected patient will have dark urine and blackish discoloration of connective tissue, especially cartilage and bone and hence it is known as black bone disease.
PRESENTATION OF THE CASE
The reported case is for 49 years old gentleman, known to have hypertension, hypothyroidism and Alkaptunurea. He presented to our facility with long standing bilateral knee pain (more in the left) with difficulty in doing daily activities. He presented to our tertiary facility after failure of previous treatment measures. The patient underwent uncomplicated Robotic assisted total knee arthroplasty that resulted in significant improvement of his pain and function.
CONCLUSION
Knee arthroplasty is a reliable and reproducible modality in treating Ochronotic knee arthropathy and it would result in pain reduction and better function of patients with such condition.
PubMed: 32554281
DOI: 10.1016/j.ijscr.2020.06.005 -
Case Reports in Orthopedics 2019Ochronosis arthropathy (OcA) is a rare condition which may be treated with total knee arthroplasty (TKA) at the end stage. The condition is often discovered only...
INTRODUCTION
Ochronosis arthropathy (OcA) is a rare condition which may be treated with total knee arthroplasty (TKA) at the end stage. The condition is often discovered only intraoperatively and the ideal choice of TKA is unknown.
CASE PRESENTATION
A 54-year-old male with worsening chronic bilateral mechanical knee pain had failed conservative therapy. Posterior stabilised (PS), cemented TKA and patella resurfacing was performed. Intraoperatively, collagenous structures such as the menisci and cartilage were noted to be black. Histological examination showed deposition of large amorphous brown material suggestive of ochronosis. He recovered well and underwent TKA of the contralateral knee the following year. At 2 years postindex TKA, his outcome scores improved and he was satisfied.
DISCUSSION AND CONCLUSION
With increasing TKA performed worldwide, a surgeon may eventually be surprised by the above findings once in their lifetime. However, OcA may be considered a likely diagnosis and it is safe to proceed with TKA. There is no particular TKA design that proved to be superior in our systematic review of 19 publications regarding TKA as all reported good outcomes. However, as the pathogenesis of OcA appears to be inflammatory in nature, we suggest using cemented PS TKA with resurfacing of the patella.
PubMed: 31687244
DOI: 10.1155/2019/1871856 -
Scientific Reports Nov 2021Alkaptonuria (AKU), a rare genetic disorder, is characterized by the accumulation of homogentisic acid (HGA) in organs due to a deficiency in functional levels of the... (Comparative Study)
Comparative Study
Alkaptonuria (AKU), a rare genetic disorder, is characterized by the accumulation of homogentisic acid (HGA) in organs due to a deficiency in functional levels of the enzyme homogentisate 1,2-dioxygenase (HGD), required for the breakdown of HGA, because of mutations in the HGD gene. Over time, HGA accumulation causes the formation of the ochronotic pigment, a dark deposit that leads to tissue degeneration and organ malfunction. Such behaviour can be observed also in vitro for HGA solutions or HGA-containing biofluids (e.g. urine from AKU patients) upon alkalinisation, although a comparison at the molecular level between the laboratory and the physiological conditions is lacking. Indeed, independently from the conditions, such process is usually explained with the formation of 1,4-benzoquinone acetic acid (BQA) as the product of HGA chemical oxidation, mostly based on structural similarity between HGA and hydroquinone that is known to be oxidized to the corresponding para-benzoquinone. To test such correlation, a comprehensive, comparative investigation on HGA and BQA chemical behaviours was carried out by a combined approach of spectroscopic techniques (UV spectrometry, Nuclear Magnetic Resonance, Electron Paramagnetic Resonance, Dynamic Light Scattering) under acid/base titration both in solution and in biofluids. New insights on the process leading from HGA to ochronotic pigment have been obtained, spotting out the central role of radical species as intermediates not reported so far. Such evidence opens the way for molecular investigation of HGA fate in cells and tissue aiming to find new targets for Alkaptonuria therapy.
Topics: Acetates; Adult; Aged; Alkaptonuria; Benzoquinones; Case-Control Studies; Dynamic Light Scattering; Electron Spin Resonance Spectroscopy; Female; Homogentisate 1,2-Dioxygenase; Homogentisic Acid; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Mutation; Ochronosis; Oxidation-Reduction; Spectrophotometry, Ultraviolet; Urinalysis
PubMed: 34799606
DOI: 10.1038/s41598-021-01670-z -
Autopsy & Case Reports Sep 2020Ochronosis is a cutaneous disorder caused by the accumulation of phenols, either endogenously as homogentisic acid in patients with alkaptonuria (autosomal recessive...
Exogenous Ochronosis (EO): Skin lightening cream causing rare caviar-like lesion with banana-like pigments; review of literature and histological comparison with endogenous counterpart.
Ochronosis is a cutaneous disorder caused by the accumulation of phenols, either endogenously as homogentisic acid in patients with alkaptonuria (autosomal recessive disorder with deficiency of the enzyme homogentisic acid oxidase), or exogenously in patients using phenol products such as topical creams containing hydroquinone or the intramuscular application of antimalarial drugs. Exogenous ochronosis (EO) typically affects the face and was reported in patients with dark skin such as Black South Africans or Hispanics who use skin-lightening products containing hydroquinone for extended periods. Recently more cases have been reported worldwide even in patients with lighter skin tones, to include Eastern Indians, Asians, and Europeans. However, just 39 cases of EO have been reported in the US literature from 1983 to 2020. Here we present two cases; a 69 and a 45-year-old female who were seen for melasma, given hydroquinone 4% cream daily and tretinoin 0.05%. Both patients noticed brown spots on their cheeks, which progressively enlarged and darkened in color. The diagnosis of ochronosis was confirmed by characteristic histopathological features on the punch biopsy. Unfortunately, neither patient responded to multiple treatments (to include, tazarotene 0.1% gel and pimecrolimus ointment, topical corticosteroids, and avoidance of hydroquinone containing products). We also present a case of classic (endogenous) ochronosis in a patient with alkaptonuria to picture the histological similarities of these two entities. EO is an important clinical consideration because early diagnosis and treatment may offer the best outcome for this notoriously refractory clinical diagnosis.
PubMed: 33344320
DOI: 10.4322/acr.2020.197 -
Surgical Neurology International 2022Alkaptonuria (AKU) is a rare hereditary disorder in which excess homogentisic acid (HGA) deposits in connective tissues (ochronosis). Here, we report the unusual...
BACKGROUND
Alkaptonuria (AKU) is a rare hereditary disorder in which excess homogentisic acid (HGA) deposits in connective tissues (ochronosis). Here, we report the unusual presentation of a lumbar disc herniation occurring in a patient with AKU warranting surgical intervention.
CASE DESCRIPTION
A 28-year-old male presented with 1 year of low back pain. The lumbar magnetic resonance imaging showed an extruded disc at the L4-L5 level accompanied extensive disc space narrowing and osteophyte formation. At surgery, the interspinous ligaments, facet joints, and disc herniation were black. In addition, the postoperative re-examination revealed a black discoloration of the nasal and ear cartilage. Finally, the diagnosis of AKU was confirmed when the urine specimen was positive for HGA.
CONCLUSION
Rarely, younger patients with AKU who develop excess black deposits of HGA in connective tissues (i.e., ochronosis) may present with lumbar disc herniations and spondylosis.
PubMed: 35127215
DOI: 10.25259/SNI_1178_2021 -
Medicine Aug 2019Alkaptonuria (AKU) is a rare disease caused by deficiency of homogentisate 1,2-dioxygenase which results in deposition of homogentisic acid (HGA). Ochronotic arthritis,...
INTRODUCTION
Alkaptonuria (AKU) is a rare disease caused by deficiency of homogentisate 1,2-dioxygenase which results in deposition of homogentisic acid (HGA). Ochronotic arthritis, the deposition of excess oxidized HGA in the connective tissues, causes pigmentation and degeneration of the joint tissues ultimately resulting in chronic inflammation and osteoarthritis. The ochronotic arthritis has similar clinical features with osteoarthritis. There is currently no specific treatment for AKU and management is usually symptomatic. In severe cases, total joint arthroplasty is the major treatment approaches. It is rarely reported in China.
PATIENT CONCERNS
Here we reported a case of a patient with bilateral knee pain for more than 1 year. He complained of a 20-year history of chronic, nonspecific low back pain and stiffness. His urine was black since he was a child. Six years after the knee surgery, his Achilles tendon ruptured.
DIAGNOSIS
Specific radiographic and magnetic resonance imaging manifestations were observed. Darkly pigmented full-thickness cartilage and subchondral bone were found during the operation. Histological investigation also manifested dark stains in meniscus and synovial tissues. Black-denatured tendon tissue was also found during the operation. The patient was diagnosed as AKU.
INTERVENTIONS
Total knee arthroplasty and Achilles tendon repair were operated separately after the disease was diagnosed.
OUTCOMES
The patient recovered very well after the second surgery. He returned to full activities, described no knee pain, and presented to the clinic walking without any aid. Physical examination revealed 0 to 20 of plantar flexion and 0 to 15 of dorsiflexion of the ankle.
CONCLUSIONS
Ochronosis is a very rare disease in Asia. This paper supplies new information for study of this disease. The mechanism is still unknown right now. Further studies will be necessary.
Topics: Achilles Tendon; Alkaptonuria; Arthroplasty, Replacement, Knee; Cartilage, Articular; Disease Progression; Humans; Knee Joint; Magnetic Resonance Imaging; Male; Middle Aged; Ochronosis; Rupture, Spontaneous
PubMed: 31441856
DOI: 10.1097/MD.0000000000016837