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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
25
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
Service de néphrologie pédiatrique, Hôpital Femme Mère Enfant, Hospices Civils de Lyon
Bron, France
RECRUITINGService de Néphrologie pédiatrique, Hôpital Jeanne de Flandre
Lille, France
RECRUITINGService de néphrologie et exploration fonctionnelle rénale, Hôpital Edouard Herriot, Hospices Civils de Lyon
Lyon, France
RECRUITINGService de Néphrologie pédiatrique, Hôpital de la Timone
Marseille, France
RECRUITINGService de Néphologie et endocrinologie pédiatrique, Hôpital Arnaud de Villeneuve
Montpellier, France
RECRUITINGService de Néphrologie pédiatrique, Hôpital Necker-Enfants Malades
Paris, France
RECRUITINGService de Néphrologie-transplantation rénale adultes, Hôpital Necker-Enfants Malades
Paris, France
RECRUITINGService de Néphrologie pédiatrique, Hôpital Robert Debré
Paris, France
RECRUITINGService de Néphrologie-Dialyse-Transplantation pédiatrique, Hôpital d'enfants Brabois
Vandœuvre-lès-Nancy, France
RECRUITINGMembrane 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.
Time frame: 24 months
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.
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 24 months
EAT10 (Eating Assessment Tool) questionnaire score
EAT10 (Eating Assessment Tool) questionnaire score is pathological if \>= 3 : * 3-10 mild dysphagia * 11-20 moderate dysphagia * 21-40 severe dysphagia) questionnaire. EAT10 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 grip-test score
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 24 months
Distribution of plasma organic amino acids
Study of metabolomic analysis of patients' blood
Time frame: 24 months
Distribution of urinary organic amino acids
Study of metabolomic analysis of patients' urine
Time frame: 24 months
Urinary Krebs cycle intermediate metabolites
Study of metabolomic analysis of patients' urine
Time frame: 24 months
Membrane potential of circulating monocyte cells from patients treated with selenium
Mitochondrial metabolism was assessed by measuring the membrane potential by flow cytometry of circulating monocyte cells from patients with cystinosis treated with selenium
Time frame: 30 months
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