Ear, nose, and throat manifestations of alkaptonuria patients from Jordan

Al-Shagahin, Hani; Mwafi, Nesrin; Khasawneh, Mahmoud; Zubi, Khalid Al; Alsbou, Mohammad

doi:10.4103/indianjotol.indianjotol_23_19

Cited by 7 publications

(3 citation statements)

References 13 publications

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“…In the present study, the former mentioned sign was observed in the adult patients, whereas ear wax was observed in both adult and paediatric patients. Furthermore, hearing impairments were diagnosed in 33% of the adult patients [ 21 ]. All the enrolled patients had dark urine on standing; since darkening may not occur for several hours after voiding, many patients never observe such abnormal colouration of their urine.…”

Section: Discussionmentioning

confidence: 99%

Variant Analysis of Alkaptonuria Families with Significant Founder Effect in Jordan

Khalil

Ali

Mwafi

et al. 2021

BioMed Research International

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Background. Metabolic disorder alkaptonuria is an autosomal recessive disorder caused by mutations in the HGD 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 HGD 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 HGD 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 HGD gene. Additionally, we correlated the clinical and genetic features of AKU patients at various ages (3-60 years).

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Section: Discussionmentioning

confidence: 99%

Variant Analysis of Alkaptonuria Families with Significant Founder Effect in Jordan

Khalil

Ali

Mwafi

et al. 2021

BioMed Research International

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“…This happens due to mutations inhomogentisate 1,2-dioxygenase(HGD) gene located on the longarm of chromosome 3 and subsequent deficiency in functional HGD enzyme (Khalil et al, 2021;Mwafi et al, 2021a). Although AKU is globally classified as a rare disease (incidence of 1:250,000), its prevalence is considered high in certain ethnicity such as Slovakian, Dominican, Indian and Jordanian population (Alsbou and Mwafi, 2013;Al-Shagahin et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Renal Calculi Composition in Alkaptonuria: Insights on Etiology

2023

JJBS

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Alkaptonuria is a rare genetic disease caused by defect in the phenylalanine and tyrosine metabolism due to a deficiency in homogentisate 1,2-dioxygenase enzyme. The formation of ochronotic brownish-black pigment is the hallmark of the disease and at later stage AKU patients complain of recurrent renal calculi formation. In this report, we describe the case of 48 years old man who is previously diagnosed with alkaptonuria and is suffering from recurrent renal stones formation. We analysed the chemical composition of his AKU-stones by Fourier transform infrared spectroscopy (FTIR) and Inductively coupled plasma-mass spectrometry (ICP-MS) respectively and compared them with non-AKU stones obtained from 48 years old non-AKU man. Our results showed that sulphur content was 33 folds higher in AKU stones compared to non-AKU sample. This provides an evidence that sulphur-rich protein is a critical component for stone formation and growth from calcium oxalate monohydrate (COM) crystals. Accordingly, a model was proposed for the formation and growth of ochronotic renal stones in AKU patients with protein stimulated COM aggregation based on the generation of adducts between benzoquinone acetate and sulphur-rich proteins. Overall, the outcomes of this study shed a new light on the disease pathogenesis at the molecular level and opened new perspective which might orient the physicians to find a convenient therapeutic intervention or at least prophylactic measures to avoid recurrent formation of calculi in AKU patients.

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“…One of the earliest signs of alkaptonuria is urine that turns black or dark brown upon standing for 24 h or after exposure to air [ 5 ]. Other presentations of alkaptonuria are bluish discoloration of the ear auricle, black cerumen, dark spots in the eye sclera, staining of the teeth, blue speckled discoloration of the skin, rupture of Achilles tendon, and renal and prostatic stones [ 9 , 10 , 11 ]. Rupture of the Achilles tendon is reported in the literature as a rare clinical complication usually occurring in male patients with alkaptonuria [ 12 , 13 ].…”

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Alkaptonuria with extensive ochronotic degeneration of the Achilles tendon and its surgical treatment: a case report and literature review

et al. 2021

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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.

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Ear, nose, and throat manifestations of alkaptonuria patients from Jordan

Cited by 7 publications

References 13 publications

Variant Analysis of Alkaptonuria Families with Significant Founder Effect in Jordan

Variant Analysis of Alkaptonuria Families with Significant Founder Effect in Jordan

Renal Calculi Composition in Alkaptonuria: Insights on Etiology

Alkaptonuria with extensive ochronotic degeneration of the Achilles tendon and its surgical treatment: a case report and literature review

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