Alkaptonuria: clinical manifestations and an updated approach to treatment of a rare disease

2021 ◽  
Vol 14 (12) ◽  
pp. e244240
Author(s):  
Ryan Curtis Roopnarinesingh ◽  
Noel Edward Donlon ◽  
John V Reynolds
Keyword(s):  
Rare Disease ◽  
Enzymatic Degradation ◽  
Autosomal Recessive ◽  
Clinical Manifestations ◽  
Autosomal Recessive Disorder ◽  
Cartilage Destruction ◽  
Homogentisic Acid ◽  
Connective Tissues ◽  
Tendon Ruptures ◽  
Published Research

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.

scholarly journals Sequential tendon ruptures in ochronosis: case report

2017 ◽  
Vol 3 (6) ◽  
pp. 1235
Author(s):  
E. G. Mohan Kumar ◽  
G. M. Yathisha Kumar
Keyword(s):  
Connective Tissue ◽  
Case Reports ◽  
Autosomal Recessive Disorder ◽  
Degradation Pathway ◽  
Homogentisic Acid ◽  
The Body ◽  
Acid Oxidase ◽  
Connective Tissues ◽  
Dark Pigmentation ◽  
Tendon Ruptures

<p>Alkaptonuria is a rare autosomal recessive disorder characterised by the absence of homogentisic acid oxidase, due to deficiency of an enzyme that degrades HGA in the tyrosine degradation pathway. Homogentisic acid (HGA) and its metabolites accumulate in the connective tissues leading to dark pigmentation of connective tissue in patients with alkaptonuria. HGA deposits in connective tissue causes weakness of the tendon and subsequent rupture, especially the large tendons in the body. Only few cases are reported in the literature with multiple tendon rupture but many case reports are available with isolated rupture of tendons. We report on a patient with sequential tendon ruptures in a patient. The case is reported for its rarity.</p>

Papillon-Lefevre Syndrome: Challenge for Periodontal Management

2019 ◽  
Vol 3 (2) ◽  
pp. 84-86
Author(s):  
Krishna Prasad Lamichhane ◽  
Shaili Pradhan ◽  
Ranjita Shreshta Gorkhali ◽  
Pramod Kumar Koirala
Keyword(s):  
Significant Role ◽  
Autosomal Recessive ◽  
Clinical Manifestations ◽  
Autosomal Recessive Disorder ◽  
Genetic Mutations ◽  
Rare Autosomal Recessive Disorder ◽  
Diagnosis And Management ◽  
Periodontal Destruction ◽  
Palmoplantar Keratosis

Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder associated with rapidly progressing periodontitis leading to premature loss of deciduous and permanent dentition and diffuse palmoplantar keratosis. Immunologic alterations, genetic mutations, and role of bacteria are some aetiologic factors. Patients present with early periodontal destruction, so periodontists play a significant role in diagnosis and management. This paper reports a case of Papillon- Lefevre syndrome with its clinical manifestations and challenges for periodontal management which was diagnosed in dental department.

Ellis-van Creveld Syndrome and Dyserythropoiesis

2005 ◽  
Vol 129 (5) ◽  
pp. 680-682 ◽  
Author(s):  
Deven Scurlock ◽  
Daniel Ostler ◽  
Andy Nguyen ◽  
Amer Wahed
Keyword(s):  
Myelodysplastic Syndrome ◽  
Autosomal Recessive ◽  
Ectodermal Dysplasia ◽  
Case Reports ◽  
Clinical Manifestations ◽  
Autosomal Recessive Disorder ◽  
Clinical Findings ◽  
Cardiac Defects ◽  
Ellis Van Creveld Syndrome ◽  
Syndrome Association

Abstract Ellis-van Creveld (EVC) syndrome or chondroectodermal dysplasia is a rare autosomal recessive disorder characterized by a variable spectrum of clinical findings. Classical EVC syndrome comprises a tetrad of clinical manifestations of chondrodystrophy, polydactyly, ectodermal dysplasia, and cardiac defects. In several case reports, dysplasia involving other organs has also been identified. Hematologic abnormalities have been rarely reported in patients with EVC syndrome. Here, we report a case of a 3-year-old Hispanic boy with EVC syndrome and marked dyserythropoiesis. The dyserythropoiesis may be part of an isolated myelodysplastic change or a primary myelodysplastic syndrome and likely represents an unusual EVC syndrome association. To our knowledge, this association has not been previously reported.

scholarly journals Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency: late diagnosis and gender reassignment in a two-year-old child

2021 ◽  
Vol 67 (5) ◽  
pp. 53-57
Author(s):  
N. Yu. Raygorodskaya ◽  
E. P. Novikova ◽  
A. N. Tyulpakov ◽  
M. A. Kareva ◽  
N. A. Nikolaeva ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Clinical Case ◽  
Clinical Manifestations ◽  
Autosomal Recessive Disorder ◽  
Compound Heterozygous ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Gender Reassignment ◽  
And Gender ◽  
21 Hydroxylase Deficiency

11β-hydroxylase deficiency is a rare autosomal recessive disorder due to impaired steroidogenesis in the adrenal cortex caused by pathogenic mutations in the CYP11B1 gene. The main clinical manifestations are determined by a deficiency of cortisol, ACTH hyperproduction, excessive androgens secretion and the accumulation of 11-deoxycorticosterone, which leads to the development of arterial hypertension. In the diagnostic search, it is important to take into account the ethnicity of the patient, since the frequency of the disease and the prevalence of mutations differ between ethnic groups. The article presents a clinical case of 11β-hydroxylase deficiency as the result of compound heterozygous mutations in the CYP11B1 gene in a patient of Turkic origin. This case shows the clinical manifestations and the development of complications of 11β-hydroxylase deficiency, the stages of differential diagnosis of patients with 21-hydroxylase deficiency.

scholarly journals Alkaptonuria

2017 ◽  
Vol 49 (1-2) ◽  
pp. 37-39
Author(s):  
Md Nazrul Islam ◽  
SM Kamal ◽  
Sk Amir Hossain ◽  
Sirajul Islam
Keyword(s):  
Back Pain ◽  
Male Patient ◽  
Joint Pain ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Homogentisic Acid ◽  
Multiple Nodules

Alkaptonuria is a rare metabolic autosomal recessive disorder. It occurs due to lack of an enzyme that results in deposition of homogentisic acid in various tissues. A male patient of 45 years presented with back pain for 20 years and multiple joint pain for 10 years. Patient has multiple nodules in both pinnae and pigmentation in both sclerae. His urine turns black upon standing. These findings are compatible with the diagnosis of Alkaptonuria.Bang Med J (Khulna) 2016; 49 : 37-39

scholarly journals SPONTANEOUS ACHILLES TENDON RUPTURE - A CASE OF OCHRONOSIS

2013 ◽  
Vol 03 (03) ◽  
pp. 113-115 ◽  
Author(s):  
Sanath Kumar Shetty ◽  
Raj Sankar N. R. ◽  
Nirmal Babu P. ◽  
Lawrence J. Mathias ◽  
Shubha P. Bhat ◽  
...  
Keyword(s):  
Achilles Tendon ◽  
Spontaneous Rupture ◽  
Autosomal Recessive ◽  
Tendon Rupture ◽  
Achilles Tendon Rupture ◽  
Autosomal Recessive Disorder ◽  
Intervertebral Discs ◽  
Homogentisic Acid ◽  
Acid Oxidase ◽  
Articular Cartilages

AbstractAlkaptonuria is a rare autosomal recessive disorder characterised by the absence of homogentisic acid oxidase and the subsequent accumulation of homogentisic acid, a metabolic product of the aromatic aminoacids phenylalanine and tyrosine; which is deposited in articular cartilages, intervertebral discs, sclera, tympanic membrane, tendons and ligaments leading to their degeneration. Here we describe a case of spontaneous rupture of Achilles tendon1,2,3 due to Ochronosis.

scholarly journals Sensenbrenner Syndrome Presenting with Severe Anorexia, Failure to Thrive, Chronic Kidney Disease and Angel-Shaped Middle Phalanges in Two Siblings

2021 ◽  
pp. 1-5
Author(s):  
Miroslava Brndiarova ◽  
Martin Mraz ◽  
Zuzana Kolkova ◽  
Frantisek Cisarik ◽  
Peter Banovcin
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Autosomal Recessive ◽  
Primary Cilia ◽  
Tubulointerstitial Nephritis ◽  
Clinical Manifestations ◽  
Failure To Thrive ◽  
Autosomal Recessive Disorder ◽  
Functional Development ◽  
Sensenbrenner Syndrome

Sensenbrenner syndrome is a very rare autosomal recessive disorder caused by variants in genes involved in the functional development of primary cilia. Typical clinical manifestations include craniofacial and skeletal abnormalities, hence the alternative name cranioectodermal dysplasia. Chronic kidney disease due to progressive tubulointerstitial nephritis (nephronophthisis) has been described in these patients. The authors present 2siblings with severe anorexia, failure to thrive, chronic kidney disease, and angel-shaped middle phalanges. Two previously described variants p.(Leu641*) and p.(Asp841Val) were identified in the <i>WDR35</i> gene which is most commonly affected in this condition. Analysis of all coding exons of the <i>GDF5</i> gene was normal. This is the first report of Sensenbrenner syndrome presenting with severe anorexia and failure to thrive at early age. Angel-shaped middle phalanges in the absence of the <i>GDF5</i> variant may represent an overlapping phenotypic manifestation of ciliopathy.

scholarly journals A Newborn Infant With Poor Feeding: Non-ketotic Hyperglycinemia

2019 ◽  
Vol 7 (4) ◽  
pp. 134-136
Author(s):  
Masoumeh Ghesmati ◽  
Alireza Jashni Motlagh
Keyword(s):  
Cerebrospinal Fluid ◽  
Metabolic Disorder ◽  
Autosomal Recessive ◽  
Genetic Test ◽  
Clinical Manifestations ◽  
Autosomal Recessive Disorder ◽  
Neonatal Onset ◽  
Glycine Metabolism ◽  
Newborn Girl ◽  
Rare Metabolic Disorder

Non-ketotic hyperglycinemia (NKH) is a rare autosomal recessive disorder affecting glycine metabolism that is a rare metabolic disorder in infants. The clinical manifestations of poor sucking, hypotonicity, lethargy, hiccups, and seizures develop within six hours to eight days of the birth of an otherwise healthy newborn. The present study introduced a newborn girl with poor feeding and hypotonia in the first day after birth with NKH. In addition, the patient was evaluated regarding hypotonia and poor feeding. The neonatal-onset NKH was diagnosed based on a markedly elevated cerebrospinal fluid/plasma glycine ratio of 0.32 and confirmed by the genetic test. It is extremely rare that NKH is manifested with poor feeding and hypotonia thus considering this diagnosis in infants with poor feeding and hypotonia is highly important.

scholarly journals Wilson's disease: A rare autosomal recessive disorder of copper metabolism

2014 ◽  
Vol 4 (2) ◽  
pp. 51-53
Author(s):  
RR Pradhan ◽  
J Gupta
Keyword(s):  
Autosomal Recessive ◽  
Wilson’S Disease ◽  
Clinical Manifestations ◽  
Copper Toxicity ◽  
Copper Metabolism ◽  
Autosomal Recessive Disorder ◽  
Wilson's Disease ◽  
Medical College ◽  
Ocular Manifestations ◽  
Membrane Bound

Wilson’s disease is an autosomal recessive disorder caused by mutations in the ATP7B gene, a membrane-bound copper-transporting ATPase. Clinical manifestations are caused by copper toxicity and primarily involve the liver, the brain and the eye. Because effective treatment is available, it is important to make this diagnosis early. We report a patient who developed features of neurological and ocular manifestations: incoordination and tremor and blurring of vision with presence of Kayser-Fleischer ring circling the cornea but no signs of hepatic dysfunction. DOI: http://dx.doi.org/10.3126/jcmc.v4i2.10866 Journal of Chitwan Medical College 2014; 4(2): 51-54

scholarly journals Two Siblings with Kaufman Oculocerebrofacial Syndrome Resembling Oculoauriculovertebral Spectrum

2021 ◽  
Vol 12 (2) ◽  
pp. 106-111
Author(s):  
Gizem Ürel-Demir ◽  
Büşra Aydın ◽  
Beren Karaosmanoğlu ◽  
Özlem Akgün-Doğan ◽  
Ekim Zihni Taşkıran ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Autosomal Recessive Disorder ◽  
Pathogenic Mutation ◽  
Genetic Alterations ◽  
High Rate ◽  
Facial Features ◽  
Psychomotor Delay ◽  
Oculoauriculovertebral Spectrum

Kaufman oculocerebrofacial syndrome is a rare autosomal recessive disorder which represents a phenotype mainly involving craniofacial and neurodevelopmental manifestations due to <i>UBE3B</i> gene mutations. The vast majority of the affected individuals exhibit microcephaly, eye abnormalities, and typical facial gestalt including blepharophimosis, ptosis, telecanthus, upslanting palpebral fissures, dysplastic ears, and micrognathia. We encountered 2 siblings in whom severe psychomotor delay, distinctive facial features, hearing loss, and respiratory distress were observed. Some clinical manifestations of the patients, including epibulbar dermoid, microtia, and multiple preauricular tags, were reminiscent of the oculoauriculovertebral spectrum. However, 2 affected siblings exhibited a similar clinical picture consisting of microcephaly, severe developmental and cognitive disabilities, failure to thrive, and dysmorphic features, which were not fully consistent with oculoauriculovertebral spectrum. Also, hypoplastic nails, considered as a core manifestation of Coffin-Siris syndrome, were present in our patients. Therefore, whole-exome sequencing was carried out in order to identify the underlying genetic alterations, contributing to the complex phenotype shared by the 2 siblings. A homozygous pathogenic mutation was found in both affected siblings in the <i>UBE3B</i> gene which caused Kaufman oculocerebrofacial syndrome. Kaufman oculocerebrofacial syndrome should be considered among the autosomal recessive causes of blepharophimosis-mental retardation syndromes, particularly in populations with a high rate of consanguineous marriages, even if there are dysmorphic facial features that are not typically associated with the phenotype.

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