Alkaptonuria in Turkey: Clinical and molecular characteristics of 66 patients

Kisa, Pelin Teke; Gündüz, Mehmet; Dorum, Sevil; Uzun, Özlem Ünal; Çakar, Nafiye Emel; Yıldırım, Gonca; Erdol, Sahin; Hismi, Burcu; Tuğsal, Handan Yarkan; Görükmez, Özlem; Küçükçongar, Aynur; Bülbül, Selda; Sarı, İ̇smail; Arslan, Nur

doi:10.1016/j.ejmg.2021.104197

Cited by 10 publications

(11 citation statements)

References 24 publications

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“…Similar observations in children with AKU were published previously. 13,29 Internal ochronosis could therefore also be present in tissues under greater stress such as spine and joints, known to be more susceptible to ochronosis. The imaging of joints was not designed to look for ochronosis in the knee joint.…”

Section: Discussionmentioning

confidence: 99%

Clinical presentation of 13 children with alkaptonuria

Kujawa

Świętoń

Wierzba

et al. 2023

J of Inher Metab Disea

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Until now, only a few studies have focused on the early onset of symptoms of alkaptonuria (AKU) in the pediatric population. This prospective, longitudinal study is a comprehensive approach to the assessment of children with recognized AKU during childhood. The study includes data from 32 visits of 13 patients (five males, eight females; age 4–17 years) with AKU. A clinical evaluation was performed with particular attention to eye, ear, and skin pigmentation, musculoskeletal complaints, magnetic resonance imaging (MRI), and ultrasound (US) imaging abnormalities. The cognitive functioning and adaptive abilities were examined. Molecular genetic analyses were performed. The most common symptoms observed were dark urine (13/13), followed by joint pain (6/13), and dark ear wax (6/13). In 4 of 13 patients the values obtained in the KOOS‐child questionnaire were below the reference values. MRI and US did not show degenerative changes in knee cartilages. One child had nephrolithiasis. Almost half of the children with AKU (5/13) presented deficits in cognitive functioning and/or adaptive abilities. The most frequent HGD variants observed in the patients were c.481G>A (p.Gly161Arg) mutation and the c.240A>T (p.His80Gln) polymorphism. The newly described allele of the HGD gene (c.948G>T, p.Val316Phe) which is potentially pathogenic was identified.

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Section: Discussionmentioning

confidence: 99%

Clinical presentation of 13 children with alkaptonuria

Kujawa

Świętoń

Wierzba

et al. 2023

J of Inher Metab Disea

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“…Wu and Hu 10.3389/fsurg.2022.913120 metabolites is relatively mild, patients may have no obvious symptoms except for skin pigmentation and the changes in urine color (7). However, as AKU progresses and connective tissue is affected, Gil et al pointed out that the intervertebral discs of the spine may be affected first, followed by the weight-bearing joints of the extremities, which may cause low back pain and degenerative changes in the knee and hip joints (8).…”

Section: Discussionmentioning

confidence: 99%

Total knee arthroplasty and physical therapy for arthropathy in alkaptonuria: A 4-year follow-up case report

Wu¹,

2023

Front. Surg.

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IntroductionAlkaptonuria is a rare autosomal recessive metabolic disorder which leads to accumulation of homogentisic acid in the body.Case PresentationWe 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.ResultThe 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.ConclusionIt 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.

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“…Although it is rare, but some AKU patients can also manifest neurological symptoms such as Parkinsonism. Basically, HGA fuse with the melanin to form a complex in substantia nigra which interferes with the formation of dopamine-melanin complex [ 22 ]. Patients may also suffer from depression due to physical impairment from pigment buildup in the skin, darkened urine, acute arthralgia and rigidity, and recurrent surgeries [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

“…Basically, HGA fuse with the melanin to form a complex in substantia nigra which interferes with the formation of dopamine-melanin complex [ 22 ]. Patients may also suffer from depression due to physical impairment from pigment buildup in the skin, darkened urine, acute arthralgia and rigidity, and recurrent surgeries [ 22 ]. The musculoskeletal abnormalities in AKU are often deferred till the fourth decade of life and frequently precedes with the onset of spinal arthropathy [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of Potential Inhibitors for the Treatment of Alkaptonuria Using an Integrated In Silico Computational Strategy

et al. 2023

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Alkaptonuria (AKU) is a rare genetic autosomal recessive disorder characterized by elevated serum levels of homogentisic acid (HGA). In this disease, tyrosine metabolism is interrupted because of the alterations in homogentisate dioxygenase (HGD) gene. The patient suffers from ochronosis, fractures, and tendon ruptures. To date, no medicine has been approved for the treatment of AKU. However, physiotherapy and strong painkillers are administered to help mitigate the condition. Recently, nitisinone, an FDA-approved drug for type 1 tyrosinemia, has been given to AKU patients in some countries and has shown encouraging results in reducing the disease progression. However, this drug is not the targeted treatment for AKU, and causes keratopathy. Therefore, the foremost aim of this study is the identification of potent and druggable inhibitors of AKU with no or minimal side effects by targeting 4-hydroxyphenylpyruvate dioxygenase. To achieve our goal, we have performed computational modelling using BioSolveIT suit. The library of ligands for molecular docking was acquired by fragment replacement of reference molecules by ReCore. Subsequently, the hits were screened on the basis of estimated affinities, and their pharmacokinetic properties were evaluated using SwissADME. Afterward, the interactions between target and ligands were investigated using Discovery Studio. Ultimately, compounds c and f were identified as potent inhibitors of 4-hydroxyphenylpyruvate dioxygenase.

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Alkaptonuria in Turkey: Clinical and molecular characteristics of 66 patients

Cited by 10 publications

References 24 publications

Clinical presentation of 13 children with alkaptonuria

Clinical presentation of 13 children with alkaptonuria

Total knee arthroplasty and physical therapy for arthropathy in alkaptonuria: A 4-year follow-up case report

Identification of Potential Inhibitors for the Treatment of Alkaptonuria Using an Integrated In Silico Computational Strategy

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