-
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 -
BioMed Research International 2021Metabolic disorder alkaptonuria is an autosomal recessive disorder caused by mutations in the gene, and a deficiency HGD enzyme activity results in an accumulation of...
BACKGROUND
Metabolic disorder alkaptonuria is an autosomal recessive disorder caused by mutations in the gene, and a deficiency HGD enzyme activity results in an accumulation of homogentisic acid (HGA), ochronosis, and destruction of connective tissue.
METHODS
We clinically evaluated 18 alkaptonuria patients (age range, 3 to 60 years) from four unrelated families. Furthermore, 11 out of 18 alkaptonuria patients and 7 unaffected members were enrolled for molecular investigations by utilizing Sanger sequencing to identify variants of the 14 exons of gene.
RESULTS
We found that the seven patients from the 4 unrelated families carried a recurrent pathogenic missense variant (c.365C>T, p. Ala122Val) in exon 6 of gene. The variant was fully segregated with the disease in affected family members while the other unaffected family members were heterozygous carriers for this variant. Additionally, the clinical features were fully predicted with alkaptonuria disorder.
CONCLUSION
In this study, we confirmed that the most common variants in Jordanian AKU patients was c.365C>T, p. Ala122Val in exon 6 of gene. Additionally, we correlated the clinical and genetic features of AKU patients at various ages (3-60 years).
Topics: Adolescent; Adult; Alkaptonuria; Child; Child, Preschool; Exons; Family Health; Female; Founder Effect; Genes, Recessive; Genetic Variation; Heterozygote; Homogentisate 1,2-Dioxygenase; Homogentisic Acid; Humans; Jordan; Male; Middle Aged; Mutation, Missense; Ochronosis; Oligonucleotides; Pedigree; Sequence Analysis, DNA; Young Adult
PubMed: 34235214
DOI: 10.1155/2021/1515641 -
The Thoracic and Cardiovascular Surgeon... Jan 2021Alkaptonuria is a rare autosomal recessive genetic disorder of tyrosine metabolism, which results in accumulation of homogentisic acid in various tissues, including...
Alkaptonuria is a rare autosomal recessive genetic disorder of tyrosine metabolism, which results in accumulation of homogentisic acid in various tissues, including the cardiovascular system. We report on a 64-year-old man with mixed aortic valve disease who underwent conventional aortic valve replacement. Intraoperative aortotomy revealed black pigmentation of the intima of the ascending aorta and the aortic valve was observed with thickened and calcified dark black leaflets. Histopathological diagnosis of ochronosis of the aortic valve was made. Despite several previous signs and symptoms, the diagnosis of alkaptonuria was not established until aortic valve replacement.
PubMed: 34194920
DOI: 10.1055/s-0041-1728721 -
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 -
Molecular Genetics and Metabolism... Jun 2021A 34-year old woman with alkaptonuria had an elective pregnancy, during which she collected urine samples over the duration of her pregnancy until parturition. She had...
A 34-year old woman with alkaptonuria had an elective pregnancy, during which she collected urine samples over the duration of her pregnancy until parturition. She had been attending the National Alkaptonuria Centre from the age of 31 years and continued to attend after delivery for a further three annual visits. Data from her NAC visits as well as urine samples collected during pregnancy were analysed. Urine CTX-1/urine creatinine, urine αCTX-I/ urine creatinine, urine CTX-II/ urine creatinine, and urine C3M/urine creatinine all showed a rapid increase early in pregnancy, returning to baseline before increasing in late pregnancy, indicating significant remodelling of bone, subchondral bone, cartilage and other organs and connective tissue rich in collagens I, II and III. The pattern of tissue remodelling in AKU pregnancy has been described for the very first time. Further research is needed to understand pregnancy in AKU.
PubMed: 33996493
DOI: 10.1016/j.ymgmr.2021.100766 -
Indian Dermatology Online Journal 2021Dermatoscopy is a non-invasive, handy tool, which is increasingly being used in diagnosis and prognostication of pigmentary dermatoses. Dermatoscopic changes in...
Dermatoscopy is a non-invasive, handy tool, which is increasingly being used in diagnosis and prognostication of pigmentary dermatoses. Dermatoscopic changes in pigmentary pattern, scaling, and vasculature help us to differentiate among the myriad of hypo and hyper pigmentary diseases. This review gives a brief overview of the dermatoscopic features of pigmentary diseases, which are commonly encountered in clinical practice. We also provide a diagnostic approach based on salient dermatoscopic features.
PubMed: 33768020
DOI: 10.4103/idoj.IDOJ_561_20 -
Journal of Orthopaedic Case Reports Nov 2020Alkaptonuria is a rare metabolic disorder of autosomal recessive pattern of inheritance caused due to homogentisic acid oxidase enzyme deficiency. As a result, polymers...
INTRODUCTION
Alkaptonuria is a rare metabolic disorder of autosomal recessive pattern of inheritance caused due to homogentisic acid oxidase enzyme deficiency. As a result, polymers of homogentisic acid get deposited in excessive amounts in the connective tissues, leading to brownish-black pigmentation termed as ochronosis. As the disease progresses, chronic inflammation results in arthritis of large weight-bearing joints.
CASE REPORT
A 70-year-old female patient presented with complaints of being non-ambulatory since the past 10 days. She gave a history of difficulty in walking for the past 10-15 years associated with pain in the right hip which did not respond to analgesics and physiotherapy. The radiological assessment revealed severe joint destruction of the right hip. The patient underwent a total hip arthroplasty. A provisional diagnosis of ochronosis was made intraoperatively which was later confirmed on histopathological examination of the tissue.
CONCLUSION
At present, there is still no known effective medical treatment to halt alkaptonuria entirely. Ochronotic arthropathy is usually managed conservatively. However, for severely involved hip joints, arthroplasty can provide extremely good results.
PubMed: 33708713
DOI: 10.13107/jocr.2020.v10.i08.1860 -
Current Allergy and Asthma Reports Mar 2021Ochronosis and alkaptonuria are manifestations of the same condition-a rare autosomal recessive disorder resulting from a constitutional lack of homogentisate... (Review)
Review
PURPOSE OF REVIEW
Ochronosis and alkaptonuria are manifestations of the same condition-a rare autosomal recessive disorder resulting from a constitutional lack of homogentisate 1,2-dioxygenase (HGD) with the consequent accumulation of homogentisic acid (HGA). In ochronosis, HGA undergoes autoxidation as well as enzymatic oxidation to form an ochronotic pigment that accumulates in cartilage and connective tissues. In the beginning, there is homogentisic aciduria and pigmentation of cartilages and other connective tissues. In later years, generalized osteoarthritis of the spine and large joints, termed ochronotic arthropathy, develops.
RECENT FINDINGS
The diagnosis is confirmed by quantitative measurement of HGA in urine and mutation analysis of the HGD gene. One of the differential diagnoses for the skin findings is exogenous ochronosis, a limited hyperpigmentation of skin caused by some chemicals. As for the lumbar spine findings, there can be radiographic similarities with ankylosing spondylitis (AS) including reduced intervertebral disc spaces and loss of lumbar lordosis; however, ochronosis will spare the sacroiliac joint, and the lumbar spine will show dense, wafer-like disk calcification with a vacuum disc phenomenon and broad syndesmophytes. Here, we present a case of a patient with probable ochronosis that was treated many years as ankylosing spondylitis without response, and we provide a review of the current literature on ochronosis pathogenesis, diagnosis, and treatment.
Topics: Alkaptonuria; Animals; Homogentisic Acid; Humans; Ochronosis; Spondylitis, Ankylosing
PubMed: 33666743
DOI: 10.1007/s11882-021-01002-1 -
BMJ Case Reports Feb 2021Alkaptonuria is a rare genetic disorder resulting in abnormality of tyrosine metabolism. It is one of the Garrod's tetrad of 'inborn errors of metabolism' proposed to...
Alkaptonuria is a rare genetic disorder resulting in abnormality of tyrosine metabolism. It is one of the Garrod's tetrad of 'inborn errors of metabolism' proposed to have Mendelian recessive inheritance. The disorder is characterised by deposition of homogentisic acid leading to ochronosis and ochronotic osteoarthropathy; however, blackish discoloration of urine is the only childhood manifestation. Other manifestations present only after third decade. A 13-year-old boy presented to paediatric nephrology clinic with blackish discolouration of urine since infancy. Examination revealed bluish black discolouration of bilateral sclera and ear cartilage; however, he had no symptoms of ochronotic osteoarthropathy. Genetic test pointed towards alkaptonuria. Currently, he is on regular follow-up and is being treated with vitamin C to delay the progression of the disease. Early diagnosis with appropriate intervention delays the onset of complications and preserves the quality of life of the patient.
Topics: Adolescent; Alkaptonuria; Antioxidants; Ascorbic Acid; Disease Progression; Early Diagnosis; Humans; Male; Ochronosis; Sclera
PubMed: 33541951
DOI: 10.1136/bcr-2020-240147