Worldwide disparities in access to treatment and investigations for nephropathic cystinosis: a 2023 perspective.

BACKGROUND: Nephropathic cystinosis (NC) is a rare lysosomal disease, leading to early kidney failure and extra-renal comorbidities. Its prognosis strongly relies on early diagnosis and treatment by cysteamine. Developing economies (DEing) face many challenges when treating patients for rare and chronic diseases. The aim here is to evaluate the access to investigations and treatment in DEing, and to assess for potential inequalities with Developed Economies (DEed). METHODS: In this international cross-sectional study, a questionnaire on access, price and reimbursement of genetic, biological analyses, and treatment was sent to nephrology centers worldwide during 2022. RESULTS: A total of 109 centers responded, coming from 49 countries and managing 741 patients: 43 centers from 30 DEing and Economies in transition (TrE), and 66 from 19 DEed. In 2022, genetics availability was 63% in DEing and 100% in DEed, whereas intra leukocytes cystine levels (IL-CL) were available for 30% of DEing patients, and 94% of DEed patients, both increasing over the last decade, as has access to immediate release cysteamine and to cysteamine eye drops in DEing. However, delayed released cysteamine can be delivered to only 7% vs. 74% of patients from DEing and DEed, respectively, and is still poorly reimbursed in DEing. CONCLUSIONS: Over the last decade, access to investigations (namely genetics and IL-CL) and to cysteamine have improved in DEing and TrE. However, discrepancies remain with DEed: access to delayed released cysteamine is limited, and reimbursement is still profoundly insufficient, therefore limiting their current use.

Biomarkers of sickle cell nephropathy in Senegal.

Sickle cell anemia (SCA) is caused by a single point variation in the ß-globin gene (HBB): c.20A> T (p.Glu7Val), in homozygous state. SCA is characterized by sickling of red blood cells in small blood vessels which leads to a range of multiorgan complications, including kidney dysfunction. This case-control study aims at identifying sickle cell nephropathy biomarkers in a group of patients living with SCA from Senegal. A total of 163 patients living with SCA and 177 ethnic matched controls were investigated. Biological phenotyping included evaluation of glycemia, glucosuria, albuminuria, proteinuria, tubular proteinuria, serum creatinine, urine creatinine, urine specific gravity and glomerular filtration rate. Descriptive statistics of biomarkers were performed using the χ2 -test, with the significance level set at p<0.05. Patients living with SCA had a median age of 20 years (range 4 to 57) with a female sex frequency of 53.21%. The median age of the control participants was 29 years (range: 4-77) with a female sex frequency of 66.09%. The following proportions of abnormal biological indices were observed in SCA patients versus (vs.) controls, as follows: hyposthenuria: 35.3%vs.5.2% (p<0.001); glomerular hyperfiltration: 47.66%vs.19.75% (p<0.001), renal insufficiency: 5.47%vs.3.82% (p = 0.182); microalbuminuria: 42.38%vs.5.78% (p<0.001); proteinuria: 39.33%vs.4.62% (p<0.001); tubular proteinuria: 40.97%vs.4.73% (p<0.001) and microglucosuria: 22.5%vs.5.1% (p<0.001). This study shows a relatively high proportion of SCA nephropathy among patients living with SCA in Senegal. Microglucosuria, proteinuria, tubular proteinuria, microalbuminuria, hyposthenuria and glomerular hyperfiltration are the most prevalent biomarkers of nephropathy in this group of Senegalese patients with SCA.

Effects of Senegal haplotype (Xmn1-rs7412844), alpha-thalassemia (3.7kb HBA1/HBA2 deletion), NPRL3-rs11248850 and BCL11A-rs4671393 variants on sickle cell nephropathy.

OBJECTIVE: Sickle cell anemia (SCA) can cause substantial kidney dysfunction resulting in sickle cell nephropathy, which may be affected by the presence of modifier genes. This study evaluates the effects of some modifier genes on sickle cell nephropathy. METHODS: Patients living with SCA were recruited. Alpha-thalassemia (3.7kb HBA1/HBA2 deletion) was genotyped using gap PCR multiplex. Senegal haplotype (Xmn1-rs7412844), BCL11A-rs4671393 and NPRL3-rs11248850 were genotyped using Mass Array. The effects of variants on kidney dysfunction were then evaluated using multivariate analysis. RESULTS: The number of patients living with SCA included in this study was 162 with a median age of 20 years [minimum-maximum: 4-57] and a female frequency of 53.21%. Senegal haplotype, BCL11A-rs4671393 variant were protective factors against albuminuria stage A2 with an odds ratio (OR) of 0.22 (95% CI 0.05-0.90) and 0.27 (95% CI 0.08-0.96) respectively. The combination NPRL3-rs11248850 variant - 3.7kb HBA1/HBA2 deletion was a protective factor against albuminuria stage A2 (OR = 0.087, 95% Cl 0.01-0.78) but it was a risk factor for glomerular hyperfiltration (OR = 17.69, 95% CI 1.85-169.31). CONCLUSIONS: All four variants displayed a protective effect against albuminuria stage A2. The combination alpha-thalassemia - NPRL3-rs11248850 variant is a risk factor for glomerular hyperfiltration.

[The abdominal pseudocyst: a complication of ventriculoperitoneal bypass about a case]. / Le pseudokyste abdominal : une complication de la derivation ventriculo-peritoneale à propos d'un cas.

The abdominal pseudocyst is a rare complication that can occur in subjects with a ventriculoperitoneal drain (VPD). We report the case of an 11-year-old adolescent with congenital hydrocephalus antecedent, for whom a ventriculoperitoneal shunt was made. He presented a progressive abdominal distension without notion of transit disorders. Abdominal ultrasound and uroscanner revealed an organized peritoneal effusion of great abundance, thin and regular wall, exerting a mass effect on the bladder and the ureters responsible for bilateral uretero-hydronephrosis. Above all, it has made it possible to individualize the distal ventriculo-peritoneal bypass catheter projecting in the effusion.

Le pseudokyste abdominal est une complication rare pouvant survenir chez les sujets porteurs d'une dérivation ventriculo-péritonéale (DVP). Nous rapportons le cas d'un adolescent de 11 ans, chez qui une DVP a été réalisée pour une hydrocéphalie congénitale. Il présentait une distension abdominale progressive sans notion de troubles de transit. L'imagerie (échographie, urosacnner) a permis de mettre en évidence un épanchement péritonéal de grande abondance organisé, à paroi fine et régulière, exerçant un effet de masse sur la vessie et les uretères, responsable d'une urétérohydronéphrose bilatérale. Le bout distal du cathéter de DVP a été visualisé dans la collection.

Le pseudo kyste abdominal: une complication de la dérivation ventricule péritonéale à propos d'un cas / The abdominal pseudocyst: a complication of ventriculoperitoneal bypass about a case

Le pseudokyste abdominal est une complication rare pouvant survenir chez les sujets porteurs d'une dérivation ventriculo-péritonéale (DVP). Nous rapportons le cas d'un adolescent de 11 ans, chez qui une DVP a été réalisée pour une hydrocéphalie congénitale. Il présentait une distension abdominale progressive sans notion de troubles de transit. L'imagerie (échographie, urosacnner) a permis de mettre en évidence un épanchement péritonéal de grande abondance organisé, à paroi fine et régulière, exerçant un effet de masse sur la vessie et les uretères, responsable d'une urétérohydronéphrose bilatérale. Le bout distal du cathéter de DVP a été visualisé dans la collection

The abdominal pseudocyst is a rare complication that can occur in subjects with a ventriculoperitoneal drain (VPD). We report the case of an 11-year-old adolescent with congenital hydrocephalus antecedent, for whom a ventriculoperitoneal shunt was made. He presented a progressive abdominal distension without notion of transit disorders. Abdominal ultrasound and uroscanner revealed an organized peritoneal effusion of great abundance, thin and regular wall, exerting a mass effect on the bladder and the ureters responsible for bilateral uretero-hydronephrosis. Above all, it has made it possible to individualize the distal ventriculo-peritoneal bypass catheter projecting in the effusion

Continuous ambulatory peritoneal dialysis (CAPD) in children: a successful case for a bright future in a developing country.

The authors report the first case of successful peritoneal dialysis (PD) in a developing country performed about a 13-year-old adolescent followed-up for stage V chronic kidney disease (CKD) with anuria. After 3 months of hemodialysis, the parents opted for continuous ambulatory peritoneal dialysis (CAPD) as they wished to return home located 121km from Dakar. After PD catheter insertion, the plan proposed to the patient consisted 3-4 hours stasis of isotonic dialysate during the day and a night stasis of 8 hours of icodextrin for an injection volume of 1L per session. The patient and his mother were trained and assessed on the PD technique. After dialysis adequacy was tested while hospitalised, they were able to return home and continued the sessions following the same plan prescribed and while keeping in touch, by telephone, with the medical team. The technique assessment at the day hospital every 2 weeks revealed dialysis adequacy and satisfactory tolerance of PD at home after 04 months of observation. It was the first case of successful CAPD in the pediatrics unit in this context. Scaling this technique is a challenge for the pediatric nephrologist in developing countries like Senegal.

[Interauricular communications in children: diagnosis and treatment, about 49 cases at the Children?s University Hospital in Dakar]. / Les communications interauriculaires chez l'enfant: diagnostic et prise en charge à propos de 49 cas aux CHU pédiatriques de Dakar.

Interauricular communication (IAC) is the second most important congenital heart disease in children. It accounts for 6-8% of congenital cardiac malformations in children. However, many questions are still open about this pathology. Thus, this study aims to report the prevalence rate of IAC in hospital but especially to describe its clinical, paraclinical and therapeutic aspects. For this purpose, we conducted a retrospective descriptive study. Data were collected by means of a questionnaire and then entered and analyzed in Sphinx (V5). The prevalence in Hospital was 2x1000. The average age of patients was 37 months, the sex-ratio was 0,75. No prenatal diagnosis was made. Parental consanguinity was detected in 30% of cases. Respiratory infections were found in 24% of cases. Cardiomegaly was found in 35 cases with hypervascularization in 63% of cases. Ultrasound showed a predominance of ostium secundum; wide IAC was found in 63% of cases. Pulmonary stenosis was the most important associated heart attack. Pulmonary arterial hypertension was found in 63% of the cases. Treatment was based on diuretics, which were largely used and only 7 children underwent surgery. Evolution was favorable in 39 patients reflecting a rate of 79%. Early diagnosis of IAC should be improved as well as surgical treatment of IAC affecting infants.

[Hyperthyroidism in children at the University Hospital in Dakar (Senegal)]. / L'hyperthyroïdie de l'enfant au centre hospitalier universitaire de Dakar (Sénégal).

INTRODUCTION: Hyperthyroidism in children is rare and constitutes a problem because of its psychosomatic impact. This study aimed to present an overview of the state of knowledge on these aspects in children from Dakar. METHODS: We conducted a multicenter, descriptive study over a period of 15 years. We evaluated the epidemiological, clinical and etiologic aspects of hyperthyroidism in children. RESULTS: 239 patients were included in the study with a prevalence of 2.4%, a sex ratio (M/F) of 0.36 and an average age of 10.8 years. The inclusion criteria were being the eldest son in a family(26.3%), being advanced (36.9%) or delayed (12.5%) in maturation, having short stature (40.1%). It was caused by Graves' disease in 90.3% of cases with psychoaffective factor in 22.1%. On a clinical point of view tachycardia (92.4%), goiter (91.1%), exophthalmia (81.8%), weight loss (69.8%) prevailed but with bed-wetting (30.2%) and psychic manifestations (3.1%). Cardiovascular and cutaneous manifestations were positively associated with age (p < 0.05). Goiter was associated with female sex (p = 0.005), cardiovascular (p = 0.02), neuropsychic (p = 0.03), skin (p = 0.03) signs and diarrhea (p = 0.03). Free T4 was correlated with age (p = 0.007), diarrhea (p = 0.021), anxiety (p = 0.024), heart rate (p = 0.00) and Graves' disease (p = 0.04). More voluminous the goiter, higher the free T4 (p = 0.007). CONCLUSION: Hyperthyroidism in children differs from that in adults because of induction factors, growth disturbances and enuresis. Age and sex seem to favor the clinical picture of thyrotoxicosis and its associated signs.

[Idiopathic nephrotic syndrome (INS) in children in Dakar: about 40 cases]. / Le syndrome néphrotique idiopathique (SNI) de l'enfant à Dakar: à propos de 40 cas.

INTRODUCTION: This study aimed to analyze the diagnostic, therapeutic, and evolutionary features of nephrosis in children in a pediatric department in Dakar. METHODS: The study was carried out in the Department of Pediatrics at the Aristide Le Dantec Hospital. We conducted a retrospective study over a period of 3 years from 1 January 2012 to 31 December 2014. All patients aged 2-12 years with idiopathic nephrotic syndrome were included in the study. RESULTS: Forty cases of nephrosis were collected, that is to say a prevalence of 23% among patients with kidney disease treated in the Department of Pediatrics. The average age was 7.11 ± 3.14 years. 72.5% (n=29) of patients suffered from pure nephrotic syndrome. Lower limb edema was present in 100% of patients, oliguria in 55% (n=22) and high blood pressure (HBP) in 5% (n=2) of cases. Median proteinuria was 145,05 ± 85,54 mg/kg/24 hours. Median protidemia was 46,42 ±7.88 g/L and median albumin was 17.90 ± 7.15 g/L. Thirty nine patients were treated with prednisone-based corticosteroid therapy. Corticosensitivity was retained in 77% (n=30) patients and corticoresistance in 13% (n=5) of cases. The factor of poor response after corticosteroid therapy was initial proteinuria greater than 150 mg/kg/day (p = 0.024). Renal biopsy was performed in 18% (n=7) of patients which showed focal and segmental hyalinosis in 57.2% (n=4). Cyclophosphamide and azathioprine were associated with corticosteroids in 10% (n=4) of cases respectively. The overall remission rate was 89.8%. The evolution toward chronic renal failure was observed in three patients. CONCLUSION: Nephrosis accounted for almost one quarter of all cases of kidney disease treated in our Department. It has high overall remission rate. The only factor contributing to poor response after corticosteroid therapy was high levels of initial proteinuria. Focal and segmental hyalinosis was the most frequently found lesion diagnosed by renal biopsy.

[Difficulties in the management of cerebral venous thrombosis (CVT) complicated by subarachnoid hemorrhage (SAH) in infants: about a case]. / Difficultés de la prise en charge d'une thrombose veineuse cérébrale (TVC) compliquée d'hémorragie sous arachnoïdienne (HSA) chez le nourrisson: à propos d'un cas.

CVT is generally rare, particularly among infants. The occurrence of a SAH associated with CVT is very uncommon and only a few cases have been reported in the literature. Symptoms are variable and often misleading. Outcome can be lethal or it can cause potentially severe sequelae if it is not treated or treated late. We report the case of a 22-month old infant examined for convulsions with Stage II coma, intracranial hypertension syndrome and infectious syndrome. Laboratory tests showed pseudomonas spp sepsis and cerebral CT scan allowed the diagnosis. Treatment was based on antibiotic therapy but mainly on anticoagulation therapy. The patient had a significant clinical improvement and follow-up cerebral CT scan showed disappearance of thrombosis with sequellar right hemoragic images. CVT is a severe disease, usually of infectious origin. Anticoagulant therapy is controversial, in particular in patients with associated hemorrhage, but clinical experience supports the effectiveness and safety of this treatment.

[Epidemiological, clinical and hematological profiles of homozygous sickle cell disease during the intercritical period among children in Ziguinchor, Senegal]. / Profils épidemiologiques, cliniques et hématologiques de la drépanocytose homozygote SS en phase inter critique chez l'enfant à Ziguinchor, Sénégal.

Sickle cell disease poses a public health problem in Senegal. It mainly affects children and adolescents. This study aimed to determine the epidemiological, clinical and hematological profiles of homozygous (SS) sickle cell disease in a cohort of children followed-up at the Peace Hospital in Ziguinchor. We conducted a retrospective study of the medical records from children with sickle cell disease. All patients aged between 2 months and 21 years with sickle cell disease SS during the intercritical period, hospitalized during the study period from 1st January 2015 to 31 August 2017 were included in our study. Compound heterozygous patients (SC, S Beta Thalassemia) were not included. We collected 46 medical records of patients with sickle cell disease SS (20 girls and 26 boys). The average age of children was 8,0 years [11 months-21 years]. Approximately 1/3 of children (39.1%) had an age less than or equal to 5 years. There was an ethnic diversity showing a predominance of the Diola (30.2%) followed by the Mandinga (27.9%) and the Poular (25.6%). The average age of children with first crisis was 35,5 months [7-192 months]. More than 1/3 of children (41.3%) had had first crisis before their second anniversary. In the child, first crisis was dominated by vaso-occlusive crisis (32.6%) followed by hand-foot syndrome (30.4%). Clinical signs during the intercritical period were pallor 95.6%), jaundice (36.9%) and splenomegaly (21.7%). Mean white blood cell count was 12465 leucocytes/mm3 [5340-26900]. Hyperleukocytosis greater than 10 000 leucocytes/mm3was found in 34 patients (73.9%). All patients had anemia with an average hemoglobin of 08,6 g/dl [05,7-11,8]. Hemoglobin S rate ranged between 54.6 and 98.4%. Diagnosis and medical management of sickle cell disease SS are delayed in Ziguinchor. Neonatal screening may lead to improve early management of patients in the region.

[Hemolytic-uremic syndrome (HUS) in children at the University Hospital Center in Dakar: about four cases]. / Syndrome hémolytique et urémique de l'enfant au Centre Hospitalier Universitaire (CHU) de Dakar: à propos de quatre observations.

Hemolytic-uremic syndrome (HUS) is a common cause of organic acute renal failure (ARF) in children. It is a progressive complication of acute gastroenteritis (AGE), especially caused by Escherichia coli in children. This study aimed to describe the clinical, therapeutic and evolutionary aspects of this affection in four children. We collected four cases of HUS. The average age was 10,5 months (5-15mois), exclusively boys. Clinical examination revealed a hemolytic anemia (pallor and jaundice), oligoanuria and edematous syndrome (2 cases), arterial hypertension (1 patient), AGE associated with severe dehydration and hypovolemic shock (2 patients), consciousness disorders. ARF was found in all patients as well as thrombocytopenia and schizocytes smear. Direct Coombs test was negative. Hyperkalemia was found in 3 patients, of whom 1 with hyperkalemia level of more than 9.2 mmol/L, hyponatremia at 129 mmol/l (1 patient) and hypernatremia at 153 mmol/l (1 patient). HUS was secondary to pneumococcal pneumonia (1 patient) while AGE was secondary to E. coli (1 patient). The treatment was mainly symptomatic and included fluid restriction, transfusion of red cell concentrates, diuretics, peritoneal dialysis and hemodialysis. The evolution was marked by the onset of chronic renal failure (1 patient) after 6 months of follow-up and by recovery (1 case). Three patients died. HUS is the most common cause of organic acute renal failure in newborns. Diagnosis is essentially biological, treatment is mostly symptomatic.

[Congenital hypothyroidism in Dakar: about 28 cases]. / Hypothyroïdie congénitale à Dakar: à propos de 28 cas.

Child hypothyroidism has been little studied in Senegal. The aim of this study was to evaluate the epidemiological, diagnostic and evolutionary aspects of congenital hypothyroidism. We conducted a descriptive-analytical retrospective study of all children treated for congenital hypothyroidism at the Albert-Royer National Children's Hospital Center over the period from 2001 to 2014 (14 years). We collected and analyzed socio-demographic, clinical and evolutionary data from patient medical records. A total of 28 patients were included in the study, an average of 2 cases per year. The average age of discovery of hypothyroidism was 54.25 ± 43 months with a female predominance (Sex-ratio 0.47). Only 2 cases of hypothyroidism were diagnosed in the neonatal period. Consanguinity was present in 68% of patients. Clinical signs were dominated by the delay in psychomotor acquisitions (96%), hypothermia (46%), cranio-facial dysmorphia (43%) and goiter (39%). Growth retardation was constant beyond 6 months. The etiologies were dominated by hormonosynthesis disorders (84.21%). During the study period, mean SD of patients had decreased from -3.5 SD to -2.25 SD for a median treatment duration of 28 months. Mental retardation was present in 73% of cases. Growth retardation and mental retardation were more severe as the diagnosis was late. Our results confirm the inadequacy of early management of patients. It is urgent to implement a routine neonatal screening system in order to improve the mental prognosis of this condition.

[Portal cavernoma in children revealed by gastrointestinal haemorrhage: about a case]. / Cavernome portal chez l'enfant révélé par une hémorragie digestive: à propos d'un cas.

Portal cavernoma is a venous vascular anomaly characterized by the formation of a network of veins whose caliber is increased and carrying portal blood. It is due to a thrombotic and always chronic occlusion of the extra-hepatic portal venous system. This is one of the most common causes of portal hypertension in children. Its severity is mainly associated with an high risk of gastrointestinal haemorrhage. Very few cases have been described mainly in African literature. We report the case of a 4-year old boy admitted with very abundant haematemesis, melena and dizziness associated with anemic syndrome on examination. Laboratory tests showed severe microcytic hypochromic anemia with normal renal and hepatic function. Gastrointestinal endoscopy showed esophageal varices (grade III) with red signs. Abdominal ultrasound showed portal vein formation resulting in the classic "spiderweb", in favor of a cavernoma. Abdominal CT scan confirmed portal cavernoma associated with portal hypertensive syndrome and vascular anomaly like an ectopic splenic vein anastomosis with the trunk formed by the gonadal vein and the inferior mesenteric vein. Therapeutic approach was based on blood transfusion and beta-blocker treatment. Portal cavernoma can be a major complication of vascular malformations often unknown. In case of gastrointestinal haemorrhage in children, diagnosis should be suspected. Its management requires early treatment and should be adapted to the patient's condition in order to prevent a fatal evolution.