Article
Biochemistry & Molecular Biology
Lakshminarayan R. Ranganath, Andrew T. Hughes, Andrew S. Davison, Milad Khedr, Richard Imrich, Mattias Rudebeck, Birgitta Olsson, Brendan P. Norman, George Bou-Gharios, James A. Gallagher, Anna M. Milan
Summary: This study investigated the effects of nitisinone on the metabolites in the PHE/TYR pathway. It was found that treatment with nitisinone significantly increased the concentrations of metabolites from the tyrosine metabolic pathway.
Article
Biochemistry & Molecular Biology
Jake Littman, John Pietro, Jon Olansen, Chanika Phornphutkul, Roy K. Aaron
Summary: Endogenous ochronosis, also known as alkaptonuria, is a rare disease characterized by bluish-black discoloration of the skin and urine, and joint degradation. This report presents a case of an 83-year-old female with alkaptonuria and provides an overview of the pathophysiological mechanisms of the disease.
Article
Endocrinology & Metabolism
L. R. Ranganath, T. Heseltine, M. Khedr, M. F. Fisher
Summary: In a large cohort of alkaptonuria (AKU) patients, a high prevalence of aortic valve disease was found to be strongly associated with ochronosis and disease severity. Nitisinone was shown to decrease ochronosis and had a significant effect on Vmax.
MOLECULAR GENETICS AND METABOLISM
(2021)
Article
Endocrinology & Metabolism
Ayse Ergul Bozaci, Havva Yazici, Ebru Canda, Sema Kalkan Ucar, Merve Saka Guvenc, Afig Berdeli, Sara Habif, Mahmut Coker
Summary: This study retrospectively evaluated the clinical, laboratory, molecular findings, and treatment characteristics of 35 patients with alkaptonuria. The study found that 24 males and 11 females from 32 different families were diagnosed with alkaptonuria. The study also identified 11 different genetic variants, including 6 novel ones. The findings suggest that a low-protein diet can reduce urinary excretion of homogentisic acid.
JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM
(2022)
Review
Medicine, Research & Experimental
Nesrin Mwafi, Ali Alasmar, Monther Al-Momani, Sattam Alazaydeh, Omar Alajoulin, Mohammad Alsalem, Heba Kalbouneh
Summary: Alkaptonuria is a rare genetic metabolic disorder characterized by the accumulation of homogentisic acid and its pigmented polymer in the body, leading to tissue discoloration. This case report highlights a surgical treatment approach for Achilles tendon pain in this condition and discusses the successful outcomes post-surgery.
Article
Medicine, General & Internal
Mohit K. Singh, Faisal A. Memon, Smita A. Deokar, Yash Achhapalia, Ganesh R. Yeotiwad
Summary: This article discusses the case of an 80-year-old female patient with incidental findings of alkaptonuria, a rare genetic metabolic disorder characterized by the accumulation of homogentisic acid in the body. 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.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2023)
Article
Genetics & Heredity
L. R. Ranganath, A. M. Milan, A. C. Bay-Jensen, C. S. Thudium
Summary: A 34-year-old woman with alkaptonuria underwent an elective pregnancy, during which urine samples were collected. Analysis of the samples showed significant remodeling of bone, subchondral bone, cartilage, and other collagen-rich tissues during early pregnancy, providing new insights into the impact of pregnancy on alkaptonuria. More research is needed to understand pregnancy in alkaptonuria.
MOLECULAR GENETICS AND METABOLISM REPORTS
(2021)
Article
Surgery
Fatema A. J. AbdulKarim, Safwat M. Ibrahim, Arnold A. D. Hill, Nadeem Ajmal
Summary: Ochronosis is a rare syndrome characterized by bluish black discoloration in connective tissues due to the deposition of polymerized products of homogentisic acid. It is associated with alkaptonuria, a rare autosomal recessive metabolic disorder, and manifests as pigmentation of skin, cartilage, and sclera. This interesting case study highlights the rare occurrence of ochronosis in a woman's breasts and chest wall.
Article
Medicine, General & Internal
Anil Arora, Getnet Asnake, Karan Pandav
Summary: We report two cases of ochronotic arthritis of the knee treated with cemented total knee arthroplasty (TKA). Intraoperatively, darkened cartilage was observed and later confirmed with histopathologic examination. It is important for orthopedic surgeons to be aware of this condition as it may be unexpected. After a five-year follow-up, both cases showed improved mobility and function.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2023)
Article
Surgery
Ozgur Coban, Haci Ali Ucak, Muhammet Ahmet Guldur, Ibrahim Ozsoyler
Summary: Alkaptonuria is a rare metabolic disease characterized by the accumulation of homogentisic acid due to enzyme deficiency, leading to darkening of urine color, degenerative arthritis, and tissue pigmentation.
TURK GOGUS KALP DAMAR CERRAHISI DERGISI-TURKISH JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
(2022)
Article
Medicine, General & Internal
Aysha Habib Khan, Bushra Afroze, Hafsa Majid, Yusra Zaidi, Azeema Jamil, Lena Jafri
Summary: This study found that adult patients with Alkaptonuria often have musculoskeletal involvement, and all patients have a history of urine darkening on standing. The high prevalence of musculoskeletal involvement in patients with Alkaptonuria may be overlooked by physicians unless specifically tested for.
Article
Cell Biology
Silvia Galderisi, Vittoria Cicaloni, Maria S. Milella, Lia Millucci, Michela Geminiani, Laura Salvini, Laura Tinti, Cristina Tinti, Otilia V. Vieira, Liliana S. Alves, Alvaro H. Crevenna, Ottavia Spiga, Annalisa Santucci
Summary: Alkaptonuria is an ultra-rare disease caused by homogentisate 1,2-dioxygenase enzyme deficiency, leading to homogentisic acid accumulation in connective tissues. The alteration in AKU cartilage structure is attributed to the degeneration of the cytoskeletal network in chondrocytes caused by HGA accumulation. Analysis revealed changes in the amount and distribution of three cytoskeletal proteins in AKU chondrocyte model.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Medicine, General & Internal
Abdulla AiShenow, Clement Horteur, Regis Pailhe
Summary: Alkaptonuria (AKU) is a rare genetic metabolic disorder caused by deficiency of homogentisic acid oxidase (HGO) enzyme leading to accumulation of homogentisic acid (HGA) in the body. This case report presents a patient who experienced a spontaneous rupture of the Achilles tendon, a complication not previously reported in French and Bahraini literature.
BAHRAIN MEDICAL BULLETIN
(2022)
Article
Biochemistry & Molecular Biology
Silvia Galderisi, Martina Rossi, Vittoria Cicaloni, Ranieri Rossi, Daniela Giustarini, Ottavia Spiga, Laura Tinti, Laura Salvini, Cristina Tinti, Daniela Braconi, Lia Millucci, Pietro Lupetti, Filippo Prischi, Giulia Bernardini, Annalisa Santucci
Summary: This study evaluated the effect of homogentisic acid (HGA) on autophagy in a human chondrocytic cell line as an alkaptonuria (AKU) model. The results showed that HGA increased autophagy as a protective mechanism, but in a chronic state, HGA-induced oxidative stress decreased autophagy and activated chondrocyte apoptosis. These findings provide new perspectives for understanding the mechanism of AKU.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2022)
Article
Biochemistry & Molecular Biology
Maher Al Khatib, Jessica Costa, Daniele Spinelli, Eliana Capecchi, Raffaele Saladino, Maria Camilla Baratto, Rebecca Pogni
Summary: In this study, water soluble melanins were successfully biosynthesized from homogentisic acid and gentisic acid by the oxidative enzyme T. versicolor laccase at physiological pH. The melanins showed high antioxidant activity, persistent paramagnetism, and broad band visible light absorption. EPR analysis revealed the presence of at least two different radical species in each case, contributing to the paramagnetism observed in the samples. This achievement may have implications for understanding the composition of the ochronotic pigment in Alkaptonuria disease, and the soluble pyomelanin mimics could serve as a viable alternative to replace insoluble melanin pigment in biotechnological applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)