scholarly journals Serum Chitotriosidase level as a Novel Biomarker for Therapeutic Monitoring of Nephropathic Cystinosis among the Iraqi children

2021 ◽  
Vol 30 (1) ◽  
pp. 270-276
Author(s):  
Zainab A. Al-Kinani ◽  
Shatha H. Ali
Keyword(s):  
Fanconi Syndrome ◽  
Therapeutic Monitoring ◽  
Tubular Damage ◽  
High Morbidity ◽  
Nephropathic Cystinosis ◽  
Healthy Children ◽  
Renal Fanconi Syndrome ◽  
Therapeutic Benefits ◽  
Cystine Content ◽  
Chitotriosidase Activity

Background: Cystinosis is a rare autosomal recessive lysosomal storage disease with high morbidity and mortality. It is caused by mutations in the CTNS gene that encodes the cystine transporter, cystinosin, which leads to lysosomal cystine accumulation. It is the major cause of inherited Fanconi syndrome, and should be suspected in young children with failure to thrive and signs of renal proximal tubular damage. The diagnosis can be missed in infants, because not all signs of renal Fanconi syndrome are present during the first months of life. Elevated white blood cell cystine content is the cornerstone of the diagnosis. Since chitotriosidase (CHIT1 or chitinase-1) is mainly produced by activated macrophages both in normal and inflammatory conditions which suggest that cystinosis should be included within the differential diagnosis of disorders associated with increased plasma chitotriosidase activity. This study is aimed to estimate serum chitotriosidase level, as a screening marker and therapeutic monitor for cystinosis disease in Iraqi children with cystinosis.Subjects and Methods: The present study is a case-control study that included samples of 30 children with nephropathic cystinosis, compared to 25 healthy control children from those attending at The Genetic Rare Diseases Center / AL-Emamain AL-Kadhimain Teaching Hospital, Baghdad-Iraq.Results: Our results reported that cystinotic children had a marked elevation of serum chitotriosidase activity, compared to age-matched healthy children, besides a significant associated with leukocyte-cystine content for cystinotic patients.CHT1 as a Novel BiomarkerConclusion: Estimation of serum chitotriosidase activity might aid in monitoring the therapeutic benefits of cysteamine therapy, as well as the prognosis of the disease when WBC cystine assessment is not available.Key Words: Cystinosis, Cysteamine, Chitotriosidase.

Nephropathic cystinosis: A cause of renal fanconi syndrome

2020 ◽  
Vol 3 (1) ◽  
pp. 28
Author(s):  
Euan Soo ◽  
EugeneYu-Hin Chan ◽  
YuetPing Yuen ◽  
AlisonLap-Tak Ma
Keyword(s):  
Fanconi Syndrome ◽  
Nephropathic Cystinosis ◽  
Renal Fanconi Syndrome

scholarly journals Cell-Based Phenotypic Drug Screening Identifies Luteolin as Candidate Therapeutic for Nephropathic Cystinosis

2020 ◽  
Vol 31 (7) ◽  
pp. 1522-1537
Author(s):  
Ester De Leo ◽  
Mohamed A. Elmonem ◽  
Sante Princiero Berlingerio ◽  
Marine Berquez ◽  
Beatrice Paola Festa ◽  
...  
Keyword(s):  
Safety Profile ◽  
High Throughput Screening ◽  
Fanconi Syndrome ◽  
Lysosomal Storage Diseases ◽  
Nephropathic Cystinosis ◽  
Lysosomal Storage ◽  
Renal Fanconi Syndrome ◽  
Cystine Transporter ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular

BackgroundMutations in the gene that encodes the lysosomal cystine transporter cystinosin cause the lysosomal storage disease cystinosis. Defective cystine transport leads to intralysosomal accumulation and crystallization of cystine. The most severe phenotype, nephropathic cystinosis, manifests during the first months of life, as renal Fanconi syndrome. The cystine-depleting agent cysteamine significantly delays symptoms, but it cannot prevent progression to ESKD and does not treat Fanconi syndrome. This suggests the involvement of pathways in nephropathic cystinosis that are unrelated to lysosomal cystine accumulation. Recent data indicate that one such potential pathway, lysosome-mediated degradation of autophagy cargoes, is compromised in cystinosis.MethodsTo identify drugs that reduce levels of the autophagy-related protein p62/SQSTM1 in cystinotic proximal tubular epithelial cells, we performed a high-throughput screening on the basis of an in-cell ELISA assay. We then tested a promising candidate in cells derived from patients with, and mouse models of, cystinosis, and in preclinical studies in cystinotic zebrafish.ResultsOf 46 compounds identified as reducing p62/SQSTM1 levels in cystinotic cells, we selected luteolin on the basis of its efficacy, safety profile, and similarity to genistein, which we previously showed to ameliorate other lysosomal abnormalities of cystinotic cells. Our data show that luteolin improves the autophagy–lysosome degradative pathway, is a powerful antioxidant, and has antiapoptotic properties. Moreover, luteolin stimulates endocytosis and improves the expression of the endocytic receptor megalin.ConclusionsOur data show that luteolin improves defective pathways of cystinosis and has a good safety profile, and thus has potential as a treatment for nephropathic cystinosis and other renal lysosomal storage diseases.

Increased Plasma YKL-40 Level and Chitotriosidase Activity in Cystic Fibrosis Patients

2021 ◽  
Author(s):  
Dilara Bal Topcu ◽  
Gökcen Tugcu ◽  
Berrin Er ◽  
Sanem Eryilmaz Polat ◽  
Mina Hizal ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pediatric Patients ◽  
Adult Patients ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Children ◽  
Plasma Samples ◽  
Stable Period ◽  
Valuable Marker ◽  
Chitotriosidase Activity ◽  
Relevant Factors

Abstract Background We investigated plasma YKL-40 levels and chitotriosidase (CHIT1) activity in patients with cystic fibrosis (CF) lung disease and evaluated clinically relevant factors that may affect their levels. Methods Plasma samples were obtained from pediatric (n = 19) and adult patients (n = 15) during exacerbation, discharge and stable period of the disease. YKL-40 levels and chitotriosidase activity were measured by enzyme-linked immunosorbent assay and fluorometric assay, respectively. Data were compared with healthy children and adults of similar age. Results YKL-40 levels of pediatric and adult CF patients at all periods were significantly higher than controls (p < 0.001 and p < 0.05). CHIT1 activities of adult patients at all periods were significantly higher compared to controls (p < 0.05). On the other hand, CHIT1 activities of pediatric CF patients were similar with controls. YKL-40 levels of exacerbation period of adult CF patients were negatively correlated with % FVC (r= -0.800, p = 0.014) and % FEV1 (r= -0.735, p = 0.008). YKL-40 levels in the exacerbation period of pediatric CF patients were negatively correlated with % FVC (r= -0.697, p = 0.0082) and % FEV1 (r= -0.720, p = 0.006). Conclusions CHIT1 activity may be a valuable marker of chronic inflammation in adult CF patients who suffer from CF for a longer period of time compared to pediatric patients. Increased YKL-40 levels in both pediatric and adult patients compared to controls may point to a role in between CF pathology. Furthermore, as YKL-40 levels are correlated with FEV1 and FVC in patients, it may be useful for the monitoring of pulmonary function in CF patient.

Saethre-Chotzen Syndrome Presenting with Incomplete Renal Fanconi Syndrome

Nephron ◽  
2002 ◽  
Vol 92 (2) ◽  
pp. 463-465 ◽  
Author(s):  
Cagatay Oktenli ◽  
Mutlu Saglam ◽  
Emre Zafer ◽  
Davut Gül
Keyword(s):  
Fanconi Syndrome ◽  
Renal Fanconi Syndrome

Combined proteomic and metabonomic studies in three genetic forms of the renal Fanconi syndrome

2007 ◽  
Vol 293 (2) ◽  
pp. F456-F467 ◽  
Author(s):  
Annalisa Vilasi ◽  
Pedro R. Cutillas ◽  
Anthony D. Maher ◽  
Severine F. M. Zirah ◽  
Giovambattista Capasso ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Fanconi Syndrome ◽  
Low Molecular Weight ◽  
Renal Fanconi Syndrome ◽  
Dent’S Disease ◽  
H Nmr ◽  
Low Molecular Weight Proteinuria ◽  
Dent's Disease ◽  
Underlying Mechanisms ◽  
Normal Urine

The renal Fanconi syndrome is a defect of proximal tubular function causing aminoaciduria and low-molecular-weight proteinuria. Dent's disease and Lowe syndrome are defined X-linked forms of Fanconi syndrome; there is also an autosomal dominant idiopathic form (ADIF), phenotypically similar to Dent's disease though its gene defect is still unknown. To assess whether their respective gene products are ultimately involved in a common reabsorptive pathway for proteins and low-molecular-mass endogenous metabolites, we compared renal Fanconi urinary proteomes and metabonomes with normal (control) urine using mass spectrometry and1H-NMR spectroscopy, respectively. Urine from patients with low-molecular-weight proteinuria secondary to ifosfamide treatment (tubular proteinuria; TP) was also analyzed for comparison. All four of the disorders studied had characteristic proteomic and metabonomic profiles. Uromodulin was the most abundant protein in normal urine, whereas Fanconi urine was dominated by albumin.1H-NMR spectroscopic data showed differences in the metabolic profiles of Fanconi urine vs. normal urine, due mainly to aminoaciduria. There were differences in the urinary metabolite and protein compositions between the three genetic forms of Fanconi syndrome: cluster analysis grouped the Lowe and Dent's urinary proteomes and metabonomes together, whereas ADIF and TP clustered together separately. Our findings demonstrate a distinctive “polypeptide and metabolite fingerprint” that can characterize the renal Fanconi syndrome; they also suggest that more subtle and cause-specific differences may exist between the different forms of Fanconi syndrome that might provide novel insights into the underlying mechanisms and cellular pathways affected.

Hypophosphatemia in a Malnourished Child: When Renal Fanconi Syndrome Does Not Stand for Refeeding Syndrome

2018 ◽  
Vol 43 (1) ◽  
pp. 166-169 ◽  
Author(s):  
Joseph Runde ◽  
Edgardo Rivera‐Rivera ◽  
Cecelia Pompeii‐Wolfe ◽  
Christopher Clardy ◽  
Timothy Sentongo
Keyword(s):  
Fanconi Syndrome ◽  
Malnourished Child ◽  
Refeeding Syndrome ◽  
Renal Fanconi Syndrome

Approach to the patient with renal Fanconi syndrome, glycosuria, or aminoaciduria

2018 ◽  
Author(s):  
Detlef Bockenhauer ◽  
Robert Kleta
Keyword(s):  
Fanconi Syndrome ◽  
Tubular Dysfunction ◽  
Renal Fanconi Syndrome ◽  
Renal Glycosuria ◽  
Proximal Tubular Dysfunction ◽  
Wide Range ◽  
Proximal Tubular ◽  
Proximal Tubular Function ◽  
Low Molecular Weight Proteins ◽  
Filtration Capacity

Up to 80% of filtered salt and water is returned back into the circulation in the proximal tubule. Several solutes, such as phosphate, glucose, low-molecular weight proteins, and amino acids are exclusively reabsorbed in this segment, so their appearance in urine is a sign of proximal tubular dysfunction. An entire orchestra of specialized apical and basolateral transporters, as well as paracellular molecules, mediate this reabsorption. Defects in proximal tubular function can be isolated (e.g. isolated renal glycosuria, aminoacidurias, or hypophosphataemic rickets) or generalized. In the latter case it is called the Fanconi–Debre–de Toni syndrome, based on the initial clinical descriptions. However, in clinical practice it is usually referred to as just the ‘renal Fanconi syndrome’. Severity of proximal tubular dysfunction can vary, and may coexist with some degree of loss of glomerular filtration capacity. Causes include a wide range of insults to proximal tubular cells, including a number of genetic conditions, drugs and poisons.

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