The K
+
channel activated by the Ca
2+
, KCNN4, has been shown to contribute to red blood cell dehydration in the rare hereditary hemolytic anemia, the dehydrated hereditary stomatocytosis. We report ...two
de novo
mutations on
KCNN4
, We reported two
de novo
mutations on
KCNN4
, V222L and H340N, characterized at the molecular, cellular and clinical levels. Whereas both mutations were shown to increase the calcium sensitivity of the K
+
channel, leading to channel opening for lower calcium concentrations compared to WT KCNN4 channel, there was no obvious red blood cell dehydration in patients carrying one or the other mutation. The clinical phenotype was greatly different between carriers of the mutated gene ranging from severe anemia for one patient to a single episode of anemia for the other patient or no documented sign of anemia for the parents who also carried the mutation. These data compared to already published KCNN4 mutations question the role of KCNN4 gain-of-function mutations in hydration status and viability of red blood cells in bloodstream.
Le dépistage de la drépanocytose, la plus fréquente des hémoglobinopathies de transmission autosomique récessive, permet la détection des syndromes drépanocytaires majeurs (SDM) de type SS, SC et S ...β-thalassémie au sein d’une population ciblée. Notre objectif était d’évaluer son efficacité au centre hospitalier universitaire (CHU) de Nice.
Il s’est agi d’une étude prospective menée entre le 1er janvier 2000 et le 31 décembre 2008. Le dépistage, joint au test de Guthrie au 3e j de vie et proposé aux nouveau-nés à risque (origine ethnique et antécédents familiaux), permet la détection d’anomalies qualitatives de l’hémoglobine. Un test de confirmation est réalisé en cas de positivité. Le sexe, l’origine ethnique, le type d’hémoglobine identifiée, la zygotie, l’âge au diagnostic, la présence des familles convoquées et l’acceptation du test de confirmation ont été recueillis et analysés.
Parmi les 19 775 enfants nés au CHU de Nice pendant cette période, le dépistage, réalisé chez 7909 enfants, a détecté 151 hémoglobinopathies : 139 hétérozygotes et 12 SDM (9 SS et 3 β-thalassémies). La prévalence des SDM, sur population ciblée et totale, était respectivement de 1/659 et 1/1648 et celle des hétérozygotes de 1/57 et 1/142. Le sex-ratio était proche de 1. L’hémoglobine S dominait (74 % des hémoglobines pathogènes). Les patients étaient en majorité originaires du Maghreb et d’Afrique noire. Cent quatre familles sur 151, dont les 12 familles d’enfants SDM, se sont rendues à la consultation après réception d’un courrier de convocation. Pour 80 enfants, le test de confirmation a été accepté. Le retour d’information a été possible pour 72 de ces 80 familles.
Le nombre d’enfants dépistés ne cesse d’augmenter grâce à une meilleure implication des acteurs du dépistage. Les prévalences des SDM et des hétérozygotes observées à Nice sont similaires à celles décrites dans la littérature. Grâce au dépistage, le diagnostic, posé tôt, permet une prise en charge précoce, vers l’âge de 2 mois, avant la survenue des 1res complications, diminuant la morbi-mortalité.
Le dépistage de la drépanocytose semble efficient au CHU de Nice. Il paraît nécessaire de poursuivre les efforts de sensibilisation des personnels de santé en maternité quant à l’intérêt de ce dépistage.
Screening for sickle cell disease, the most common of recessive autosomic hemoglobin disorders, allows detection of sickle cell disease SCD (homozygous sickle cell disease, compound heterozygote SC, and S β-thalassemia) in a target population. Our objective was to evaluate its effectiveness at the Nice University Hospital.
This prospective study was conducted between 1 January 2000 and 31 December 2008. The national targeted newborn screening, run together with the Guthrie test on the 3rd day of life, offered at-risk newborns (based on ethnicity and family history), allow the detection of qualitative hemoglobin abnormalities. A confirmatory test is performed when positive. Gender, ethnicity, type of hemoglobin found, zygosity, age at diagnosis, the presence at a 2nd consultation of the families identified, and acceptance of the confirmatory test were collected and analyzed.
A total of 19,775 children were born in Nice University Hospital during this period, among whom screening detected 151 hemoglobinopathies: 139 heterozygotes and 12 major sickle cell syndrome (9 SS and 3 S β-thalassemia). The prevalence of SCD on the targeted and the total population was, respectively, 1 out of 659 and 1 out of 1648 and the prevalence of heterozygotes was 1 out of 57 and 1 out of 142. The sex ratio was close to 1. Hemoglobin S predominated (74% of pathogens Hb). The Maghreb and sub-Saharan Africa were the 2 main areas of origin. One hundred and four of 151 families, including 12 cases of SCD, returned to consultation after they received a letter requesting attendance at a 2nd consultation. For 80 children, the confirmatory test was accepted. Feedback was possible for 72 of the 80 families.
The number of children screened is increasing, thanks to better awareness among medical staff. The prevalence of SCD and heterozygotes found in Nice University Hospital is similar to what is described in the literature. With screening, early diagnosis allows early treatment at the age of 2 months before the occurrence of complications, reducing morbidity and mortality.
Screening for sickle cell disease appears effective in Nice. It seems necessary to continue focusing on the importance of screening among maternity healthcare actors.
The life expectancy of β-thalassemia patients has increased over the last 20 years. In this study, we evaluated the current health status and quality of life of these patients managed in a reference ...center in Marseille.
This is a single-center, descriptive study conducted between June and August 2019 in patients over 18 years of age with β-thalassemia major or intermedia. Clinical and paraclinical data were collected retrospectively and the SF-36 health survey questionnaire was proposed to each patient.
43 of 64 selected patients were included and divided into 2 groups: 35 patients with transfusion-dependent β-thalassemia and 8 patients with non-transfusion-dependent β-thalassemia. Liver iron overload is the most frequent complication, present in 80% of transfusion-dependent and 62.5% of non-transfusion-dependent patients. Cardiac iron overload is present only in the transfusion dependent β-thalassemia group (20%). Hypogonadotropic hypogonadism remains the most common endocrine disorder (41.9%) followed by osteoporosis (37.2%). Among the 31 patients who completed the SF-36 questionnaire, physical and mental quality of life scores were lowered in transfusion dependent (respectively 42.7 and 46.8) as in non-transfusion-dependent patients (respectively 43.8 and 28.9).
Despite an improvement in medical care, our patients with β-thalassemia show an alteration in their quality of life that will need to be characterized in the entire French cohort.
Hydration status is critical for erythrocyte survival and is mainly determined by intracellular cation content. Active pumps, passive transporters, and ion channels are the key components of volume ...homeostasis, whereas water passively fits ionic movements. Whenever cation content increases, erythrocyte swells, whereas it shrinks when cation content decreases. Thus, inappropriate cation leak causes erythrocyte hydration disorders, hemolytic anemia, and characteristic red cell shape abnormalities named stomatocytosis. All types of stomatocytosis either overhydrated or dehydrated are linked to inherited or de novo mutations in genes encoding ion transporters or channels. Although intracellular ion content can be assessed by experimental methods, laboratory diagnosis is guided by a combination of red blood cell parameters and deformability measurement when possible, and confirmed by sequencing of the putative genes. A better knowledge of the mechanisms underlying erythrocyte hydration imbalance will further lead to therapeutic improvements.
Acute liver failure (ALF) in childhood is a life-threatening emergency. ALF is often caused by drug toxicity, autoimmune hepatitis, inherited metabolic diseases, and infections. However, despite ...thorough investigations, a cause cannot be determined in approximately 50% of cases. Here, we report three cases with recurrent ALF caused by NBAS and SCYL1 pathogenic variants. These patients did not present with any other phenotypic sign usually associated with NBAS and SCYL1 pathogenic variants. Two of them underwent liver transplantation and are healthy without recurrence of ALF. We propose NBAS and SCYL1 genetic analysis in children with unexplained fever-triggered recurrent ALF even without a typical phenotype.
L’espérance de vie des patients β-thalassémiques a augmenté ces 20 dernières années. Nous avons évalué dans cette étude l’état de santé actuel et la qualité de vie de ces patients pris en charge dans ...un centre de référence à Marseille.
Il s’agit d’une étude monocentrique, descriptive menée entre juin et août 2019 chez des patients de plus de 18 ans atteints de β-thalassémie majeure ou intermédiaire. Les données cliniques et paracliniques ont été collectées rétrospectivement et un questionnaire de qualité de vie SF-36 a été proposé à chaque patient.
Sur 64 patients sélectionnés, 43 ont été inclus et repartis en 2 groupes : 35 patients thalassémiques dépendants des transfusions et 8 non-dépendants des transfusions. La surcharge hépatique en fer est la complication la plus fréquente, présente chez 80 % des thalassémiques dépendants des transfusions et 62,5 % des non dépendants des transfusions. La surcharge myocardique en fer est présente uniquement dans le groupe dépendant des transfusions (20 %). L’hypogonadisme hypogonadotrope reste l’atteinte endocrinienne la plus fréquente (41,9 %) suivie de l’ostéoporose (37,2 %). Parmi les 31 patients ayant complété le questionnaire SF-36, les scores physique et mental de qualité de vie étaient abaissés chez les thalassémiques dépendants des transfusions (respectivement 42,7 et 46,8) comme chez les non dépendants (respectivement 43,9 et 28,9).
Malgré une amélioration de leur prise en charge, nos patients β-thalassémiques montrent une altération de leur qualité de vie qu’il va falloir explorer dans l’ensemble de la cohorte française.
The life expectancy of β-thalassemia patients has increased over the last 20 years. In this study, we evaluated the current health status and quality of life of these patients managed in a reference center in Marseille.
This is a single-center, descriptive study conducted between June and August 2019 in patients over 18 years of age with β-thalassemia major or intermedia. Clinical and paraclinical data were collected retrospectively and the SF-36 health survey questionnaire was proposed to each patient.
43 of 64 selected patients were included and divided into 2 groups: 35 patients with transfusion-dependent β-thalassemia and 8 patients with non-transfusion-dependent β-thalassemia. Liver iron overload is the most frequent complication, present in 80% of transfusion-dependent and 62.5% of non-transfusion-dependent patients. Cardiac iron overload is present only in the transfusion dependent β-thalassemia group (20%). Hypogonadotropic hypogonadism remains the most common endocrine disorder (41.9%) followed by osteoporosis (37.2%). Among the 31 patients who completed the SF-36 questionnaire, physical and mental quality of life scores were lowered in transfusion dependent (respectively 42.7 and 46.8) as in non-transfusion-dependent patients (respectively 43.8 and 28.9).
Despite an improvement in medical care, our patients with β-thalassemia show an alteration in their quality of life that will need to be characterized in the entire French cohort.
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