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Cystinosis is a monogenic autosomal recessive lysosomal storage disease with complete penetrance, caused by a biallelic mutation in the CTNS gene (17p13.2) encoding cystinosin, a ubiquitous membrane protein whose role is to clear cystine into the cytosol. Its dysfunction in patients with cystinosis leads to systemic accumulation of cystine, an oxidised dimer of cysteines linked by a disulphide bridge, in the lysosomal space, and irreversible cellular dysfunction. Renal damage is at the forefront, with Fanconi syndrome (proximal tubulopathy) and chronic renal failure developing early in childhood/adolescence. There are also multi-systemic disorders, notably endocrine and ophthalmological. Cysteamine is an amino thiol which reduces the level of intra-lysosomal cystine by breaking the disulphide strands of cystine, giving two cysteines which complex with cysteamine to leave the lysosome. Since the late 1980s, there has been an immediate-release form of the drug, which has considerably improved overall patient survival despite having a major impact on quality of life. This improvement in survival has also led to the emergence of later complications that were not previously observed. This musculoskeletal complication (described in an international consensus in 2019), known as 'CMBD' for Cystinosis Metabolic Bone Disease, may be explained at least in part by an intrinsic defect in the osteoblast and osteoclast that contribute to the human bone phenotype. This intrinsic bone defect appears to be responsible for premature ageing. In order to identify potential future therapeutic targets for CMBD, it is essential to gain a better understanding of the underlying pathophysiological mechanisms.
To better understand premature aging in extra-renal damage in cystinosis, it seems relevant to investigate energy metabolism dysfunction, particularly mitochondrial dysfunction.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cystinosis patient | Other | Patient with genetically confirmed nephropathic cystinosis Men and women, children and adults with cystinosis Undergoing conservative treatment on native kidneys Age ≥ 2 years Patients receiving oral cysteamine Patients with social security coverage Informed consent signed by the participant or parents or legal guardians before participating in the study |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mitochondrial metabolism | Other | Study of membrane potential by flow cytometry of circulating monocyte cells and evaluate the respiratory chain of these cells in patients with cystinosis and described musculoskeletal disorders in the study population in clinical and biological terms including metabolomic analysis of patients' blood and urine |
| Measure | Description | Time Frame |
|---|---|---|
| Membrane potential of circulating monocyte cells | Mitochondrial metabolism was assessed by measuring the membrane potential by flow cytometry of circulating monocyte cells between subjects with and without cystinosis. | 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Oxygen consumption rate (OCR) of circulating monocytic cells | The oxygen consumption rate (OCR) of circulating monocytic cells is measured by the Seahorse method. This method also measures the extracellular acidification rate (ECAR) of cells. The oxygen consumption rate (OCR) and the extracellular acidification rate (ECAR) are used to assess the respiratory chain of the cells, which will be compared between subjects with and without cystinosis. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Justine BACCHETTA, MD | Contact | 4 27 85 61 30 | +33 | justine.bacchetta@chu-lyon.fr |
| Chloé GROSYEUX, MD | Contact | chloe.grosyeux@gmail.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Service de néphrologie pédiatrique, Hôpital Femme Mère Enfant, Hospices Civils de Lyon | Bron | 69677 Bron Cedex | France |
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| ID | Term |
|---|---|
| D003554 | Cystinosis |
| D009135 | Muscular Diseases |
| ID | Term |
|---|---|
| D016464 | Lysosomal Storage Diseases |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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| 24 months |
| Extracellular acidification rate (ECAR) of circulating monocytic cells | The extracellular acidification rate (ECAR) of circulating monocytic cells is measured by the Seahorse method. This method also measures the oxygen consumption rate (OCR) of cells. The extracellular acidification rate (ECAR) and the oxygen consumption rate (OCR) are used to assess the respiratory chain of the cells, which will be compared between subjects with and without cystinosis. | 24 months |
| Age | The patient's age is a data used to produce a clinical description of musculoskeletal disorders based on current practice data such as : sex, weight, height, blood pressure, treatment, bone deformity, clinical sign of myopathy, grip strength test using the Grip-test (Z score) and the EAT10 (Eating Assessment Tool) questionnaire | 24 months |
| Sex | The patient's sex is a data used to produce a clinical description of musculoskeletal disorders based on current practice data such as : age, weight, height, blood pressure, treatment, bone deformity, clinical sign of myopathy, grip strength test using the Grip-test (Z score) and the EAT10 (Eating Assessment Tool) questionnaire | 24 months |
| Weight | The patient's weight is a data used to produce a clinical description of musculoskeletal disorders based on current practice data such as : age, sex, height, blood pressure, treatment, bone deformity, clinical sign of myopathy, grip strength test using the Grip-test (Z score) and the EAT10 (Eating Assessment Tool) questionnaire | 24 months |
| Height | The patient's height is a data used to produce a clinical description of musculoskeletal disorders based on current practice data such as : age, sex, weight, blood pressure, treatment, bone deformity, clinical sign of myopathy, grip strength test using the Grip-test (Z score) and the EAT10 (Eating Assessment Tool) questionnaire | 24 months |
| Blood pressure | The patient's blood pressure is a data used to produce a clinical description of musculoskeletal disorders based on current practice data such as : age, sex, weight, height, treatment, bone deformity, clinical sign of myopathy, grip strength test using the Grip-test (Z score) and the EAT10 (Eating Assessment Tool) questionnaire | 24 months |
| Type of treatment | The patient's type of treatment is a data used to produce a clinical description of musculoskeletal disorders based on current practice data such as : age, sex, weight, height, blood pressure, bone deformity, clinical sign of myopathy, grip strength test using the Grip-test (Z score) and the EAT10 (Eating Assessment Tool) questionnaire | 24 months |
| Bone deformity | The patient's bone deformity is a data used to produce a clinical description of musculoskeletal disorders based on current practice data such as : age, sex, weight, height, blood pressure, treatment, clinical sign of myopathy, grip strength test using the Grip-test (Z score) and the EAT10 (Eating Assessment Tool) questionnaire | 24 months |
| Clinical sign of myopathy | Clinical sign of myopathy is a data used to produce a clinical description of musculoskeletal disorders based on current practice data such as : age, sex, weight, height, blood pressure, treatment, bone deformity, grip strength test using the Grip-test (Z score) and the EAT10 (Eating Assessment Tool) questionnaire | 24 months |
| Grip-test score | The Grip-test is used to assess grip strength. Grip-test score is a data used to produce a clinical description of musculoskeletal disorders based on current practice data such as : age, sex, weight, height, blood pressure, treatment, bone deformity, clinical sign of myopathy and the EAT10 (Eating Assessment Tool) questionnaire | 24 months |
| EAT10 (Eating Assessment Tool) questionnaire score | EAT10 (Eating Assessment Tool) questionnaire score is pathological if >= 3 :
| 24 months |
| Complete ionogram | Complete ionogram is a data used to produce biological description of musculoskeletal disorders based on routine practice data such as C-reactive protein (CRP), intra-leukocyte cystine, Parathyroid hormone (PTH), total alkaline phosphatases, 25(OH) vitamin D, 1-25 (OH) vitamin D | 24 months |
| C-Reactive Protein (CRP) | C-Reactive Protein (CRP) is a data used to produce biological description of musculoskeletal disorders based on routine practice data such as complete ionogram, intra-leukocyte cystine, Parathyroid hormone (PTH), total alkaline phosphatases, 25(OH) vitamin D, 1-25 (OH) vitamin D | 24 months |
| Intra-leukocyte cystine | Intra-leukocyte cystine is a data used to produce biological description of musculoskeletal disorders based on routine practice data such as complete ionogram, C-Reactive Protein (CRP), Parathyroid hormone (PTH), total alkaline phosphatases, 25(OH) vitamin D, 1-25 (OH) vitamin D | 24 months |
| Parathyroid hormone (PTH) | Parathyroid hormone (PTH) is a data used to produce biological description of musculoskeletal disorders based on routine practice data such as complete ionogram, C-Reactive Protein (CRP),intra-leukocyte cystine, total alkaline phosphatases, 25(OH) vitamin D, 1-25 (OH) vitamin D | 24 months |
| Total alkaline phosphatases | Total alkaline phosphatases is a data used to produce biological description of musculoskeletal disorders based on routine practice data such as complete ionogram, C-Reactive Protein (CRP), intra-leukocyte cystine, Parathyroid hormone (PTH), 25(OH) vitamin D, 1-25 (OH) vitamin D | 24 months |
| 25(OH) vitamin D | 25(OH) vitamin D is a data used to produce biological description of musculoskeletal disorders based on routine practice data such as complete ionogram, C-Reactive Protein (CRP), intra-leukocyte cystine, Parathyroid hormone (PTH), total alkaline phosphatases, 1-25 (OH) vitamin D | 24 months |
| 1-25 (OH) vitamin D | 1-25 (OH) vitamin D is a data used to produce biological description of musculoskeletal disorders based on routine practice data such as complete ionogram, C-Reactive Protein (CRP), intra-leukocyte cystine, Parathyroid hormone (PTH), total alkaline phosphatases, 25 (OH) vitamin D | 24 months |
| Distribution of plasma organic amino acids | Study of metabolomic analysis of patients' blood | 24 months |
| Distribution of urinary organic amino acids | Study of metabolomic analysis of patients' urine | 24 months |
| Urinary Krebs cycle intermediate metabolites | Study of metabolomic analysis of patients' urine | 24 months |
| Service de Néphrologie pédiatrique, Hôpital Jeanne de Flandre | Lille | 59000 | France |
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| Service de néphrologie et exploration fonctionnelle rénale, Hôpital Edouard Herriot, Hospices Civils de Lyon | Lyon | 69003 | France |
|
| Service de Néphrologie pédiatrique, Hôpital de la Timone | Marseille | 13385 | France |
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| Service de Néphologie et endocrinologie pédiatrique, Hôpital Arnaud de Villeneuve | Montpellier | 34295 | France |
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| Service de Néphrologie pédiatrique, Hôpital Necker-Enfants Malades | Paris | 75015 | France |
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| Service de Néphrologie-transplantation rénale adultes, Hôpital Necker-Enfants Malades | Paris | 75015 | France |
|
| Service de Néphrologie pédiatrique, Hôpital Robert Debré | Paris | 75019 | France |
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| Service de Néphrologie-Dialyse-Transplantation pédiatrique, Hôpital d'enfants Brabois | Vandœuvre-lès-Nancy | 54511 | France |
|
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D009140 | Musculoskeletal Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |