Sensenbrenner syndrome: a further challenge in evaluating sagittal synostosis and a need for a multidisciplinary approach.

BACKGROUND: Sensenbrenner syndrome, also known as cranioectodermal dysplasia (CED), is a genetically heterogeneous ciliopathy, characterized by dysmorphic features including dolichocephaly (with inconstant sagittal craniosynostosis), chronic kidney disease (CKD), hepatic fibrosis, retinitis pigmentosa, and brain abnormalities, with a partial clinical overlap with other ciliopathies. PATIENTS AND METHODS: A retrospective review of four children with Sensenbrenner syndrome treated at the Femme Mère Enfant University Hospital of Lyon from 2005 to 2020 was conducted. RESULTS: Variants in WDR35 or WDR19 were found in all children. Two of them underwent surgery for a scaphocephaly in the first months of life. All patients developed CKD leading to end-stage renal disease during the first/second decades. DISCUSSION: The diagnosis of scaphocephaly may precede the diagnosis of the underlying Sensenbrenner syndrome, thus highlighting the importance of a systematic multidisciplinary assessment and follow-up for craniosynostoses, in order to identify syndromic forms requiring specific management. In Sensenbrenner syndrome, patients' management should be coordinated by multidisciplinary teams of reference centers for rare diseases, with expertise in the management of craniofacial malformations as well as rare skeletal and renal disorders. Indeed, a prompt etiological diagnosis will result in an early diagnosis of multisystemic complications, notably renal involvement, thus improving global prognosis.

Bone Disease in Nephropathic Cystinosis: Beyond Renal Osteodystrophy.

Patients with chronic kidney disease (CKD) display significant mineral and bone disorders (CKD-MBD) that induce significant cardiovascular, growth and bone comorbidities. Nephropathic cystinosis is an inherited metabolic disorder caused by the lysosomal accumulation of cystine due to mutations in the CTNS gene encoding cystinosin, and leads to end-stage renal disease within the second decade. The cornerstone of management relies on cysteamine therapy to decrease lysosomal cystine accumulation in target organs. However, despite cysteamine therapy, patients display severe bone symptoms, and the concept of "cystinosis metabolic bone disease" is currently emerging. Even though its exact pathophysiology remains unclear, at least five distinct but complementary entities can explain bone impairment in addition to CKD-MBD: long-term consequences of renal Fanconi syndrome, malnutrition and copper deficiency, hormonal disturbances, myopathy, and intrinsic/iatrogenic bone defects. Direct effects of both CTNS mutation and cysteamine on osteoblasts and osteoclasts are described. Thus, the main objective of this manuscript is not only to provide a clinical update on bone disease in cystinosis, but also to summarize the current experimental evidence demonstrating a functional impairment of bone cells in this disease and to discuss new working hypotheses that deserve future research in the field.

Campylobacter Colitis as a Trigger for Atypical Hemolytic Uremic Syndrome: About One Case.

We present the case of a 17-year-old Caucasian male whose condition featured acute renal failure, anemia, and deep thrombocytopenia after five consecutive days of diarrhea. Campylobacter coli was identified in stool cultures and, although the direct role of this germ in the pathogenesis of hemolytic uremic syndrome (HUS) remains uncertain to this day, initial presentation was considered broadly consistent with typical HUS. However, the patient showed no signs of spontaneous recovery over time. While secondary investigations showed no abnormalities in ADAMTS13 activity or in the alternate pathway of complement, patient's condition deteriorated. Worsening kidney failure required emergency renal replacement therapy and was followed by cardiac involvement in the form of acute heart failure. Given this unfavorable development, blood samples were drawn to look for mutations in the alternate complement pathway, and eculizumab therapy was initiated without further delay, allowing prompt improvement of cardiac function and recovery of diuresis. Upon discharge, the patient still had to undergo intermittent dialysis, which would later be withdrawn. Genetic analysis ultimately confirmed the presence of a complement factor H mutation associated with a high risk of disease recurrence, indicating long-term continuation of eculizumab therapy.

[A complex case of renal phosphate wasting ]. / Une fuite rénale de phosphates complexe .

We describe here the case report of a young man of 34-years old suffering from a haemorrhagic rectocolitis and presenting with marked hypophosphatemia secondary to an infusion of ferric-carboxymaltose. The renal phosphate wasting was asserted by a very low renal maximal reabsorption rate of phosphate associated with a high plasma FGF-23 level. Three months later we explored the patient and his father since we learnt that both of them had suffered from kidney stones for years with marked hypercalciuria. Kidney stones were composed of weddellite and carbapatite. We suspected a familial phosphate renal wasting syndrome but however no mutation of the renal phosphate carriers could be identified.

Response to Cysteamine in Osteoclasts Obtained from Patients with Nephropathic Cystinosis: A Genotype/Phenotype Correlation.

Bone complications of cystinosis have been recently described. The main objectives of this paper were to determine in vitro the impact of CTNS mutations and cysteamine therapy on human osteoclasts and to carry out a genotype-phenotype analysis related to osteoclastic differentiation. Human osteoclasts were differentiated from peripheral blood mononuclear cells (PBMCs) and were treated with increasing doses of cysteamine (0, 50, 200 µM) and then assessed for osteoclastic differentiation. Results are presented as median (min-max). A total of 17 patients (mainly pediatric) were included, at a median age of 14 (2-61) years, and a eGFR of 64 (23-149) mL/min/1.73 m2. Most patients (71%) were under conservative kidney management (CKM). The others were kidney transplant recipients. Three functional groups were distinguished for CTNS mutations: cystinosin variant with residual cystin efflux activity (RA, residual activity), inactive cystinosin variant (IP, inactive protein), and absent protein (AP). PBMCs from patients with residual cystinosin activity generate significantly less osteoclasts than those obtained from patients of the other groups. In all groups, cysteamine exerts an inhibitory effect on osteoclastic differentiation at high doses. This study highlights a link between genotype and osteoclastic differentiation, as well as a significant impact of cysteamine therapy on this process in humans.

Comparison between citrate and acetate dialysate in chronic online hemodiafiltration: A short-term prospective study in pediatric settings.

BACKGROUND: The use of citrate in chronic hemodialysis to acidify dialysis solutions, in replacement of acetate, began in the 2000's. The purpose of the following study is to determine whether this change represents a better alternative regarding short-term tolerance, efficiency and biocompatibility of chronic renal replacement therapy (RRT) in pediatric patients. METHODS: A monocentric prospective observational study was conducted in the pediatric dialysis department of Nancy (France) between December 1st, 2014 and January 25, 2015 on a cohort of pediatric patients under predilution on-line hemodiafiltration (olHDF). Sessions were analysed during two study periods of 14 days: a first period during which dialysis solutions were acidified using acetate and a second during which solutes were acidified using citrate. These periods were separated by a washout period of 28 days on citrate solution. Each patient served as his own control. RESULTS: Dialysis clinical tolerance seems better under citrate regimen, with no statistical significance. No benefit was brought out regarding the prevention of coagulation accidents in the extracorporeal circuit under citrate regimen. The efficiency of olHDF sessions was similar between periods, both in terms of uremic toxins clearance and medium-molecular-weight molecules (MMWM) removal. The evolution of several biological parameters seemed favourable over the citrate period: increase in pre-dialysis serum bicarbonate, stability of plasma hemoglobin and decrease in erythropoietin resistance index (ERI). However, differences in the variation of these parameters between the two periods were not significant. No severe and/or symptomatic hypocalcemia occurred. CONCLUSION: The use of citrate instead of acetate in dialysis and substitution solutions appears in the short term as a safe alternative for chronic online hemodiafiltration in children.