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1.
PLoS One ; 15(4): e0232263, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32348369

RESUMO

Gentisic acid (GA), a metabolite of acetylsalicylic acid (ASA), and homogentisic acid (HGA), which is excreted at high levels in alkaptonuria, are divalent phenolic acids with very similar structures. Urine containing HGA is dark brown in color due to its oxidation. We recently reported a new oxidation method of HGA involving the addition of sodium hydroxide (NaOH) with sodium hypochlorite pentahydrate (NaOCl·5H2O), which is a strong oxidant. In the present study, we attempted to oxidize GA, which has a similar structure to HGA, using our method. We herein observed color changes in GA solution and analyzed the absorption spectra of GA after the addition of NaOH with NaOCl·5H2O. We also examined the oxidation reaction of GA using a liquid chromatography time-of-flight mass spectrometer (LC/TOF-MS). The results obtained indicated that GA solution had a unique absorption spectrum with a peak at approximately 500 nm through an oxidation reaction following the addition of NaOH with NaOCl·5H2O. This spectrophotometric method enables GA to be detected in sample solutions without expensive analytical instruments or a complex method.


Assuntos
Gentisatos/química , Espectrofotometria/métodos , Alcaptonúria/urina , Aspirina/metabolismo , Cromatografia Líquida , Gentisatos/metabolismo , Gentisatos/urina , Ácido Homogentísico/química , Humanos , Espectrometria de Massas , Oxidantes , Oxirredução , Hidróxido de Sódio , Hipoclorito de Sódio
2.
Rev Port Cir Cardiotorac Vasc ; 26(3): 225-227, 2019.
Artigo em Português | MEDLINE | ID: mdl-31734977

RESUMO

Alkaptonuria is a rare genetic disorder related to tyrosine metabolism. The cardiovascular manifestations are rare being the aortic stenosis the most commonly reported. We present a case of 72-year-old women who underwent aortic valve replacement with intraoperative findings in the aortic valve and the aortic wall suggestive of Cardiac Ochronosis. Once it is a rare disease there are issues related to the natural history of the disorder that still unknown, namely the type of aortic prothesis in use. For this reason, we find essential the documentation and follow-up of all these rare cases.


Assuntos
Alcaptonúria/complicações , Estenose da Valva Aórtica/cirurgia , Ocronose/patologia , Idoso , Valva Aórtica/patologia , Estenose da Valva Aórtica/patologia , Feminino , Implante de Prótese de Valva Cardíaca , Humanos , Ocronose/etiologia
3.
Eklem Hastalik Cerrahisi ; 30(3): 325-8, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31650933

RESUMO

Alkaptonuria is an autosomal recessive disease caused by the accumulation of homogentisic acid (HGA) products in the ligament, cartilage, skin and various organs due to the lack of HGA oxidase enzyme. In this article, we present a 61-year-old male patient operated on due to a diagnosis of spontaneous Achilles tendon rupture and diagnosed as alkaptonuria due to the intraoperative color of the tissues and the subsequent examinations. We also reviewed alkaptonuria and its accompanying pathologies in light of the literature.


Assuntos
Tendão do Calcâneo/lesões , Alcaptonúria/diagnóstico , Ocronose/diagnóstico , Acidentes por Quedas , Tendão do Calcâneo/cirurgia , Alcaptonúria/urina , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Ocronose/patologia , Ruptura Espontânea/complicações , Ruptura Espontânea/diagnóstico , Ruptura Espontânea/diagnóstico por imagem , Ruptura Espontânea/cirurgia
4.
Medicine (Baltimore) ; 98(34): e16837, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441856

RESUMO

INTRODUCTION: Alkaptonuria (AKU) is a rare disease caused by deficiency of homogentisate 1,2-dioxygenase which results in deposition of homogentisic acid (HGA). Ochronotic arthritis, the deposition of excess oxidized HGA in the connective tissues, causes pigmentation and degeneration of the joint tissues ultimately resulting in chronic inflammation and osteoarthritis. The ochronotic arthritis has similar clinical features with osteoarthritis. There is currently no specific treatment for AKU and management is usually symptomatic. In severe cases, total joint arthroplasty is the major treatment approaches. It is rarely reported in China. PATIENT CONCERNS: Here we reported a case of a patient with bilateral knee pain for more than 1 year. He complained of a 20-year history of chronic, nonspecific low back pain and stiffness. His urine was black since he was a child. Six years after the knee surgery, his Achilles tendon ruptured. DIAGNOSIS: Specific radiographic and magnetic resonance imaging manifestations were observed. Darkly pigmented full-thickness cartilage and subchondral bone were found during the operation. Histological investigation also manifested dark stains in meniscus and synovial tissues. Black-denatured tendon tissue was also found during the operation. The patient was diagnosed as AKU. INTERVENTIONS: Total knee arthroplasty and Achilles tendon repair were operated separately after the disease was diagnosed. OUTCOMES: The patient recovered very well after the second surgery. He returned to full activities, described no knee pain, and presented to the clinic walking without any aid. Physical examination revealed 0 to 20 of plantar flexion and 0 to 15 of dorsiflexion of the ankle. CONCLUSIONS: Ochronosis is a very rare disease in Asia. This paper supplies new information for study of this disease. The mechanism is still unknown right now. Further studies will be necessary.


Assuntos
Tendão do Calcâneo/lesões , Alcaptonúria/complicações , Ocronose/complicações , Tendão do Calcâneo/cirurgia , Alcaptonúria/urina , Artroplastia do Joelho , Cartilagem Articular/patologia , Cartilagem Articular/cirurgia , Progressão da Doença , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Articulação do Joelho/cirurgia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Ruptura Espontânea/etiologia , Ruptura Espontânea/cirurgia
5.
Unfallchirurg ; 122(11): 905-910, 2019 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-31332451

RESUMO

This article presents the case of a 53-year-old male patient born in Sri Lanka, who presented to the outpatient unit with the suspicion of empyema of the knee joint. Within the framework of knee arthroscopy, the diagnosis of ochronosis was made and later confirmed by histopathological biopsy. The alkaptonuria is caused by a homogentisate 1,2-dioxygenase deficiency and leads to an accumulation of homogentisic acid, a degradation product of tyrosine. This leads to the characteristic appearance of ochronosis with bluish-black deposits in the tissue (e.g. in connective tissue, sclera and ear cartilage) and a black coloration of the urine.


Assuntos
Alcaptonúria/complicações , Articulação do Joelho/cirurgia , Ocronose/cirurgia , Alcaptonúria/diagnóstico , Artroscopia , Biópsia , Humanos , Articulação do Joelho/patologia , Masculino , Pessoa de Meia-Idade , Ocronose/diagnóstico , Ocronose/etiologia , Ocronose/patologia
6.
Mol Genet Metab ; 127(3): 184-190, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31235217

RESUMO

AIM: To study the efficacy of low dosage of nitisinone in alkaptonuria. BACKGROUND: Alkaptonuria (AKU) is a rare genetic disease which induces deposition of homogentisic acid (HGA) in connective inducing premature arthritis, lithiasis, cardiac valve disease, fractures, muscle and tendon ruptures and osteopenia. Recent studies showed that nitisinone decreases HGA and is a beneficial therapy in AKU. This treatment induces an increase in tyrosine levels which can induces adverse effects as keratopathy. METHODS: We described the evolution HGA excretion and tyrosine evolution in 3 AKU patients treated by very low dosage of nitisinone with regards to their daily protein intakes. We also described the first pregnancy in an AKU patient treated by nitisinone. RESULTS: We found mild clinical signs of alkaptonuria on vertebra MRI in two young adults and homogentisate deposition in teeth of a 5 years old girl. Very low dose of nitisinone (10% of present recommended dose: 0.2 mg/day) allowed to decrease homogentisic acid by >90% without increasing tyrosine levels above 500 µmol/ in these three patients. INTERPRETATIONS: The analysis of the follow-up data shows that, in our three patients, a low-dosage of nitisinone is sufficient to decrease urinary HGA without increasing plasma tyrosine levels above the threshold of 500 µmol/L.


Assuntos
Alcaptonúria/diagnóstico por imagem , Alcaptonúria/tratamento farmacológico , Cicloexanonas/administração & dosagem , Nitrobenzoatos/administração & dosagem , Adulto , Pré-Escolar , Dieta , Relação Dose-Resposta a Droga , Feminino , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Tirosina/sangue , Adulto Jovem
7.
Cornea ; 38(10): 1332-1335, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31219884

RESUMO

PURPOSE: To present a case series of patients with corneal and scleral changes associated with the use of skin-lightening creams. This is the first report of corneal changes with these widely available creams. METHODS: Three patients of West African origin presented with strikingly similar skin, corneal, and scleral changes and were found to have all been using skin-lightening creams containing hydroquinone. Histopathology was obtained for 1 patient. RESULTS: Three patients were referred to the corneal clinics of 2 hospitals with corneal changes and a history of blurred vision for 1 to 3 years. There was a 60-year-old woman from Nigeria and a 68-year-old woman and a 73-year-old man both from Ghana. All 3 had been using skin-lightening lotions containing hydroquinone on their faces for between 3 and 15 years and had black-blue facial pigmentation of exogenous ochronosis, a recognized complication of these creams. Their corneas all had horizontal striae radiating across the posterior corneas with scleral thinning and plaques. Linear brown epithelial pigmentation was observed within the lower third of the corneas. Biopsy of the sclera in 1 patient showed ochronosis. CONCLUSIONS: We present previously unreported eye changes associated with the use of skin-lightening creams containing hydroquinone, with a triad of signs: posterior corneal striae radiating from 3 o'clock to 9 o'clock, thinning and plaques in the sclera, and a normal endothelial cell count. Similar pathological changes are seen in exogenous ochronosis, a recognized skin complication of hydroquinone, are seen in the sclera.


Assuntos
Alcaptonúria/diagnóstico , Córnea/patologia , Hidroquinonas/efeitos adversos , Ocronose/diagnóstico , Esclera/patologia , Administração Tópica , Idoso , Alcaptonúria/induzido quimicamente , Biópsia , Córnea/efeitos dos fármacos , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/efeitos adversos , Feminino , Humanos , Hidroquinonas/administração & dosagem , Masculino , Pessoa de Meia-Idade , Ocronose/induzido quimicamente , Esclera/efeitos dos fármacos
8.
Ann Thorac Surg ; 108(6): e377-e379, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31181205

RESUMO

Alkaptonuria, a rare disorder of homogentisic acid metabolism, can lead to aortic valvular calcification and stenosis. This report describes the case of a 71-year-old woman with alkaptonuria-associated aortic stenosis in whom minimally invasive surgical aortic valve replacement was attempted but abandoned because of extensive aortic root calcification. She subsequently underwent transfemoral transcatheter aortic valve replacement with an Edwards SAPIEN 3 valve (Edwards Lifesciences, Irvine, CA). This report of transcatheter aortic valve replacement for treating alkaptonuria-associated aortic stenosis expands the potential treatment options for these patients.


Assuntos
Alcaptonúria/complicações , Estenose da Valva Aórtica/cirurgia , Valva Aórtica/patologia , Calcinose/etiologia , Calcinose/cirurgia , Ecocardiografia/métodos , Substituição da Valva Aórtica Transcateter/métodos , Idoso , Alcaptonúria/diagnóstico , Alcaptonúria/genética , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/etiologia , Calcinose/diagnóstico por imagem , Cateterismo Cardíaco/métodos , Feminino , Seguimentos , Humanos , Segurança do Paciente , Índice de Gravidade de Doença , Resultado do Tratamento
9.
Clin Biochem ; 71: 24-30, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31228435

RESUMO

OBJECTIVES: We have assessed the effect of elevated concentrations of hydroxyphenylpyruvic acid (HPPA), hydroxyphenyllactic acid (HPLA) and tyrosine, on a range of chemistry tests in serum and urine to explore the potential for chemical interference on routine laboratory analyses in patients with alkaptonuria (AKU) treated with nitisinone and similarly implications for patients with hereditary tyrosinemia type 1 (HT-1). MATERIALS AND METHODS: HPPA, HPLA and tyrosine were added separately to pooled serum from subjects without AKU in a range of assays with Roche Modular chemistries. Effects on urine were assessed by changes in urine strip chemistries after mixing a positive control urine with various amounts of the test compounds and reading on a Siemens urine strip meter. RESULTS: No significant effect (p > 0.1) was observed up to 225 µmol/L of HPPA and HPLA, and up to 5000 µmol/L tyrosine, on any of the serum-based assays including those with peroxidase-coupled reaction systems of enzymatic creatinine, urate, total cholesterol, HDL cholesterol and triglyceride. Both the monohydroxy HPPA, and the dihydroxy homogentisic acid (HGA), at increased urine concentrations typical of nitisinone-treated AKU and non-treated AKU respectively, did however show marked negative interference in strip assays for glucose and leucocytes; i.e. those with peroxide-linked endpoints. The effect of increased HPLA was less marked. CONCLUSIONS: In patients with AKU or on nitisinone treatment and HT-1 patients on nitisinone, urine strip chemistry testing should be used sparingly, if at all, to avoid false negative reporting. It is recommended that urine assays should be organised with a suitable specialist laboratory.


Assuntos
4-Hidroxifenilpiruvato Dioxigenase/metabolismo , Alcaptonúria/tratamento farmacológico , Alcaptonúria/metabolismo , Cicloexanonas/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Nitrobenzoatos/uso terapêutico , Fenilpropionatos/análise , Ácidos Fenilpirúvicos/análise , Tirosina/metabolismo , Alcaptonúria/sangue , Alcaptonúria/urina , Humanos , Fenilpropionatos/sangue , Fenilpropionatos/urina , Ácidos Fenilpirúvicos/sangue , Ácidos Fenilpirúvicos/urina
12.
Dermatol Online J ; 25(4)2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-31046911

RESUMO

Endogenous ochronosis (EO) or alkaptonuria is an inherited autosomal recessive disease caused by the insufficiency of the enzyme homogentisic acid dioxygenase. This disturbance causes an accumulation and increased renal excretion of homogentisic acid (AHG), which manifests as dark urine when it oxidizes on contact with air. Other clinical manifestations of OE are the result of the deposit of AHG in the form of ochronotic pigment at the level of collagen in the skin and cartilage, where it causes blue-gray cutaneous hyperpigmentation, degenerative arthropathy, valvular disease, and other multisystem effects. Despite the progressive and irreversible nature of OE and the lack of a curative treatment, the life expectancy is preserved. We report a new case of EO with cutaneous and joint involvement, in which a high clinical suspicion, confirmed by elevated AHG in urine was the key in the diagnosis.


Assuntos
Alcaptonúria/diagnóstico , Ácido Homogentísico/urina , Hiperpigmentação/etiologia , Artropatias/etiologia , Ocronose/diagnóstico , Alcaptonúria/complicações , Alcaptonúria/urina , Feminino , Humanos , Pessoa de Meia-Idade , Ocronose/etiologia
13.
J Cutan Pathol ; 46(8): 623, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31070271
14.
Ann Thorac Surg ; 108(4): e257-e259, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30926473

RESUMO

Alkaptonuria is rare genetic disorder of tyrosine metabolism manifesting with signs of tissue pigmentation, dark urine, and ochronotic arthropathies. Commonly undiscovered by late adulthood, alkaptonuria can manifest as cardiac ochronosis with cardiovascular disorders such as valvulopathies, but rarely coronary artery disease. This case report describes 2 patients with aortic stenosis and coronary artery disease in whom alkaptonuria was diagnosed during open heart surgery.


Assuntos
Alcaptonúria/complicações , Estenose da Valva Aórtica/etiologia , Doença da Artéria Coronariana/etiologia , Ocronose/etiologia , Idoso , Alcaptonúria/diagnóstico , Estenose da Valva Aórtica/cirurgia , Doença da Artéria Coronariana/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Ocronose/patologia
15.
Clin Chem ; 65(4): 530-539, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30782595

RESUMO

BACKGROUND: Identification of unknown chemical entities is a major challenge in metabolomics. To address this challenge, we developed a comprehensive targeted profiling strategy, combining 3 complementary liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) techniques and in-house accurate mass retention time (AMRT) databases established from commercial standards. This strategy was used to evaluate the effect of nitisinone on the urinary metabolome of patients and mice with alkaptonuria (AKU). Because hypertyrosinemia is a known consequence of nitisinone therapy, we investigated the wider metabolic consequences beyond hypertyrosinemia. METHODS: A total of 619 standards (molecular weight, 45-1354 Da) covering a range of primary metabolic pathways were analyzed using 3 liquid chromatography methods-2 reversed phase and 1 normal phase-coupled to QTOF-MS. Separate AMRT databases were generated for the 3 methods, comprising chemical name, formula, theoretical accurate mass, and measured retention time. Databases were used to identify chemical entities acquired from nontargeted analysis of AKU urine: match window theoretical accurate mass ±10 ppm and retention time ±0.3 min. RESULTS: Application of the AMRT databases to data acquired from analysis of urine from 25 patients with AKU (pretreatment and after 3, 12, and 24 months on nitisinone) and 18 HGD -/- mice (pretreatment and after 1 week on nitisinone) revealed 31 previously unreported statistically significant changes in metabolite patterns and abundance, indicating alterations to tyrosine, tryptophan, and purine metabolism after nitisinone administration. CONCLUSIONS: The comprehensive targeted profiling strategy described here has the potential of enabling discovery of novel pathways associated with pathogenesis and management of AKU.


Assuntos
Alcaptonúria/metabolismo , Cicloexanonas/farmacologia , Metaboloma/efeitos dos fármacos , Nitrobenzoatos/farmacologia , Idoso , Alcaptonúria/tratamento farmacológico , Animais , Cromatografia Líquida/métodos , Cromatografia Líquida/estatística & dados numéricos , Bases de Dados de Compostos Químicos , Feminino , Técnicas de Silenciamento de Genes , Homogentisato 1,2-Dioxigenase/genética , Humanos , Masculino , Espectrometria de Massas/métodos , Espectrometria de Massas/estatística & dados numéricos , Metabolômica/métodos , Camundongos , Pessoa de Meia-Idade , Fenótipo
17.
J Cutan Pathol ; 46(1): 74-79, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30294802

RESUMO

Collagenous and elastotic marginal plaques of the hand (CEMPH) is a rare, chronic keratoderma characterized by hyperkeratotic linear plaques located along the radial and ulnar aspects of the hands bilaterally. As an isolated finding, CEMPH occurs secondarily to chronic trauma and photodamage. Herein, CEMPH is described as a manifestation of alkaptonuria (AKU). In addition to keloidal collagen, ochronotic fibers and fragmented, thickened elastic fibers were observed. Additionally, mucin deposition-not previously described in this clinical context-was also identified. Given their overlapping clinicopathologic features, CEMPH due to AKU should be distinguished from the acquired variant as well as acrokeratoelastoidosis.


Assuntos
Alcaptonúria , Tecido Elástico , Mãos/patologia , Ceratodermia Palmar e Plantar , Pele , Alcaptonúria/diagnóstico , Alcaptonúria/metabolismo , Alcaptonúria/patologia , Tecido Elástico/metabolismo , Tecido Elástico/patologia , Feminino , Humanos , Ceratodermia Palmar e Plantar/diagnóstico , Ceratodermia Palmar e Plantar/metabolismo , Ceratodermia Palmar e Plantar/patologia , Pessoa de Meia-Idade , Pele/metabolismo , Pele/patologia
18.
J Neurol Surg A Cent Eur Neurosurg ; 80(2): 131-133, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30477028

RESUMO

Alkaptonuria is a rare metabolic disease caused by deficiency of homogentisic acid oxidase and characterized by bluish-black discoloration of cartilages and skin (ochronosis). Defective production of this enzyme results in the accumulation of homogentisic acid (HGA), a tyrosine degradation product, in the bloodstream. Accumulation of HGA and its metabolites in tissues causes ochronosis. The word ochronosis refers to the dark bluish-black discoloration of connective tissues including the sclera, cornea, auricular cartilage, heart valves, articular cartilage, tendons, and ligaments. Neurogenic claudication resulting from focal hypertrophy of the ligamentum flavum in the lumbar spine due to ochronotic deposits has only been previously reported once in the literature. In this article, we present a 71-year-old male patient with alkaptonuria-associated degenerative L3-L4-L5 stenosis, diagnosed after lumbar decompressive laminectomy.


Assuntos
Alcaptonúria/complicações , Ligamento Amarelo/patologia , Vértebras Lombares , Ocronose/etiologia , Idoso , Alcaptonúria/patologia , Humanos , Masculino , Ocronose/patologia
19.
J Cell Physiol ; 234(5): 6696-6708, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30341892

RESUMO

Alkaptonuria (AKU) is a disease caused by a deficient homogentisate 1,2-dioxygenase activity leading to systemic accumulation of homogentisic acid (HGA), that forms a melanin-like polymer that progressively deposits onto connective tissues causing a pigmentation called "ochronosis" and tissue degeneration. The effects of AKU and ochronotic pigment on the biomechanical properties of articular cartilage need further investigation. To this aim, AKU cartilage was studied using thermal (thermogravimetry and differential scanning calorimetry) and rheological analysis. We found that AKU cartilage had a doubled mesopore radius compared to healthy cartilage. Since the mesoporous structure is the main responsible for maintaining a correct hydrostatic pressure and tissue homoeostasis, drastic changes of thermal and rheological parameters were found in AKU. In particular, AKU tissue lost its capability to enhance chondrocytes metabolism (decreased heat capacity) and hence the production of proteoglycans. A drastic increase in stiffness and decrease in dissipative and lubricant role ensued in AKU cartilage. Multiphoton and scanning electron microscopies revealed destruction of cell-matrix microstructure and disruption of the superficial layer. Such observations on AKU specimens were confirmed in HGA-treated healthy cartilage, indicating that HGA is the toxic responsible of morphological and mechanical alterations of cartilage in AKU.


Assuntos
Alcaptonúria/tratamento farmacológico , Condrócitos/efeitos dos fármacos , Ácido Homogentísico/farmacologia , Ocronose/tratamento farmacológico , Alcaptonúria/metabolismo , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Humanos , Oxirredução/efeitos dos fármacos , Pigmentação/efeitos dos fármacos
20.
World J Pediatr ; 15(1): 4-11, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30343446

RESUMO

BACKGROUND: Bone remodeling is a lifelong process due to the balanced activity of osteoclasts (OCs), the bone-reabsorbing cells, and osteoblasts (OBs), and the bone-forming cells. This equilibrium is regulated by numerous cytokines, but it has been largely demonstrated that the RANK/RANKL/osteoprotegerin and Wnt/ß-catenin pathways play a key role in the control of osteoclastogenesis and osteoblastogenesis, respectively. The pro-osteoblastogenic activity of the Wnt/ß-catenin can be inhibited by sclerostin and Dickkopf-1 (DKK-1). RANKL, sclerostin and DKKs-1 are often up-regulated in bone diseases, and they are the target of new monoclonal antibodies. DATA SOURCES: The authors performed a systematic literature search in PubMed and EMBASE to June 2018, reviewed and selected articles, based on pre-determined selection criteria. RESULTS: We re-evaluated the role of RANKL, osteoprotegerin, sclerostin and DKK-1 in altered bone remodeling associated with some inherited and acquired pediatric diseases, such as type 1 diabetes mellitus (T1DM), alkaptonuria (AKU), hemophilia A, osteogenesis imperfecta (OI), 21-hydroxylase deficiency (21OH-D) and Prader-Willi syndrome (PWS). To do so, we considered recent clinical studies done on pediatric patients in which the roles of RANKL-RANK/osteoprotegerin and WNT-ß-catenin signaling pathways have been investigated, and for which innovative therapies for the treatment of osteopenia/osteoporosis are being developed. CONCLUSIONS: The case studies taken into account for this review demonstrated that quite frequently both bone reabsorbing and bone deposition are impaired in pediatric diseases. Furthermore, for some of them, bone damage began in childhood but only manifested with age. The use of denosumab could represent a valid alternative therapeutic approach to improve bone health in children, although further studies need to be carried out.


Assuntos
Reabsorção Óssea/fisiopatologia , Osteoprotegerina/sangue , Ligante RANK/sangue , Via de Sinalização Wnt/fisiologia , Hiperplasia Suprarrenal Congênita/sangue , Hiperplasia Suprarrenal Congênita/fisiopatologia , Alcaptonúria/sangue , Alcaptonúria/fisiopatologia , Biomarcadores/sangue , Remodelação Óssea/fisiologia , Reabsorção Óssea/sangue , Criança , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Hemofilia A/sangue , Hemofilia A/fisiopatologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Osteogênese Imperfeita/sangue , Osteogênese Imperfeita/fisiopatologia , Síndrome de Prader-Willi/sangue , Síndrome de Prader-Willi/fisiopatologia , Regulação para Cima/fisiologia
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