Accuracy of a rapid intrapartum group B Streptococcus test: A new immunochromatographic assay.

OBJECTIVES: To decrease the incidence of early-onset group B streptococcal (GBS) disease, a culture-based screening of all pregnant women at 35-37 weeks is recommended. This gold standard test requires 24-72hours culture. This delay precludes its use for intrapartum screening. This study assesses a new immunoassay, the DIMA test, for identifying GBS-positive patients in the labor ward. MATERIALS AND METHODS: This was a prospective observational study of 195 pregnant women presenting with full-term labor at a single site in France between June and August 2012. We assessed the diagnostic accuracy of intrapartum DIMA testing as compared to intrapartum GBS culture and prenatal screening at 35-38 weeks. RESULTS: The DIMA test sensitivity and specificity were 57.1% and 83.2%, respectively, as compared to 42.9% and 97% for prenatal culture screening. CONCLUSION: The DIMA test assay is a rapid and inexpensive test for the detection of maternal GBS colonization in the labor ward. Its sensitivity is higher than antepartum culture but its specificity is lower. Its performance was inferior to that reported for rapid polymerase chain reaction assays.

[Do the quality of prenatal care have an impact on obstetrical outcomes?]. / La qualité du suivi de la grossesse interfère-elle avec les issues de la grossesse, en Guadeloupe ?

OBJECTIVES: To assess the rate of pregnant women not having accurate prenatal care utilization. The others goals were to assess the impact of an inadequate quantitative or qualitative prenatal care on obstetrical outcomes. PATIENTS AND METHODS: Historical cohort study with a prospective data registration. Hospitalised patients at the maternity ward of the University Hospital of Pointe-à-Pitre were eligible if they gave birth after 22 weeks (or≥500g) at home, outside a maternity ward or in another maternity ward. Early postpartum maternal transfers were included but not medical abortions. The principal outcome was preterm birth (before 37 weeks' gestation). RESULTS: Patients without an appointment before 15weeks or without an appointment each month before their delivery represented 27.4% of women (n=2344). We stressed more preterm deliveries outside the maternity ward among the group with an inadequate prenatal care utilization vs. the other group (3,89% vs. 0,88%) (p<0,0001). We did not find any difference concerning the perinatal outcomes among the women with an inadequate quality prenatal care. DISCUSSION AND CONCLUSION: Our study did not stress a difference concerning perinatal outcomes among women with an inadequate quantitative or qualitative prenatal care utilization.

Eosinophilic activity and bronchial hyperresponsiveness within an asthmatic paediatric population

Background: Our study aims to assess the importance of serum eosinophil cationic protein (ECP) levels as a non-invasive marker of bronchial hyperresponsiveness (BHR) in children with asthma, and may predict objectively the asthmatic severity and sensitivities. Methods: This study, which was carried out on 75 asthmatic patients from a paediatric population (average age: nine years old, sex-ratio M/F: 1.64), is based on both interrogation conducted by the clinician and biological explorations, essentially serological testing of ECP and eosinophilia determination, as well as the measurement of serological IgE amounts. Results: The analysis of the questionnaires and the biological results allowed us to evaluate the clinico-biological relations within this population. ECP, more than eosinophilia, proves to be a relevant marker of asthma severity (p<0.05) and sensitivities within this given population (r=0.65). Conclusion: We were able to show that the evaluation of the serological levels of ECP seems to be a good biological marker of asthma(AU)

No disponible

Outbreak of hand, foot and mouth disease/herpangina associated with coxsackievirus A6 and A10 infections in 2010, France: a large citywide, prospective observational study.

Hand, foot and mouth disease (HFMD) and herpangina (HA) are frequently caused by several distinct serotypes belonging to the human enterovirus A species (HEVA). Enterovirus 71 is considered as a significant public health threat because of rare but fatal neurological complications. A sentinel surveillance system involving paediatricians from Clermont-Ferrand (France) was set up to determine the clinical and epidemiological characteristics of HFMD/HA associated with enterovirus infections. A standardized report form was used to collect demographic and clinical data. Throat or buccal specimens were obtained prospectively and tested for the presence of enteroviruses. The frequency of HEVA serotypes was determined by genotyping. Phylogenetic relationships were analysed to identify potential new virus variants. From 1 April to 31 December 2010, a total of 222 children were enrolled. The predominant clinical presentation was HA (63.8%) and this was frequently associated with clinical signs of HFMD (48%). An enterovirus infection was diagnosed in 143 (64.4%) patients and serotype identification was achieved in 141/143 (98.6%). The predominant serotypes were coxsackievirus A10 (39.9%) and A6 (28%), followed by coxsackievirus A16 (17.5%) and enterovirus 71 (6.3%). Fever was observed in 115 (80.4%) children. No patient had neurological complications. Coxsackievirus A10 and A6 strains involved in the outbreak were consistently genetically related with those detected earlier in Finland and constituted distinct European lineages. Although several enterovirus serotypes have been involved in HFMD/HA cases, the outbreak described in this population survey was caused by coxsackievirus A6 and coxsackievirus A10, the third dual outbreak in Europe in the last 3 years.

Eosinophilic activity and bronchial hyperresponsiveness within an asthmatic paediatric population.

BACKGROUND: Our study aims to assess the importance of serum eosinophil cationic protein (ECP) levels as a non-invasive marker of bronchial hyperresponsiveness (BHR) in children with asthma, and may predict objectively the asthmatic severity and sensitivities. METHODS: This study, which was carried out on 75 asthmatic patients from a paediatric population (average age: nine years old, sex-ratio M/F: 1.64), is based on both interrogation conducted by the clinician and biological explorations, essentially serological testing of ECP and eosinophilia determination, as well as the measurement of serological IgE amounts. RESULTS: The analysis of the questionnaires and the biological results allowed us to evaluate the clinico-biological relations within this population. ECP, more than eosinophilia, proves to be a relevant marker of asthma severity (p<0.05) and sensitivities within this given population (r=0.65). CONCLUSION: We were able to show that the evaluation of the serological levels of ECP seems to be a good biological marker of asthma.

[Emergency cervical cerclage during mid-trimester of pregnancy: Experience of Clermont-Ferrand]. / Cerclage cervical en urgence au deuxième trimestre de la grossesse : expérience clermontoise.

OBJECTIVES: The objective of this study was to identify factors associated with favourable perinatal outcome after emergency cervical cerclage during mid-trimester of pregnancy. PATIENTS AND METHODS: This is a retrospective study of all cases who underwent emergency cervical cerclage between 16 to 28 weeks of gestation (WG) over a period of 16 years in a University Hospital. RESULTS: Among the 32 cases, the postnatal survival rate (day 28) was 80%. Delivery occurred at a mean gestational age of 33.1 WG [18-41.3 WG] and after 37 WG in 39% of cases. The perinatal outcome was improved by absence of bleeding (P=0.01), unripened cervix (P=0.02), cervical dilatation below 2 cm (P=0.002), no protruding membranes (P=0.02) and more advanced gestational age at the procedure (P=0.005). When no uterine contraction and no maternal blood inflammation were observed at admission, an expectancy of 48 hours before the procedure did not improve significantly perinatal outcome (gestational age at birth and survival rate [P=0.1 and P=0.3 respectively]). DISCUSSION AND CONCLUSION: Perinatal outcome after emergency cerclage depends on cervical status and gestational age at procedure. It is not influenced by an expectancy of 48 hours before intervention for patients with no uterine contraction and no maternal blood inflammation at admission.

Assessment of left ventricular volumes and function by cine-MR imaging depending on the investigator's experience.

AIMS: To analyze the reproducibility of LV volumes calculated by cardiac magnetic resonance imaging (CMRI) and to compare them to those obtained by conventional ventriculography. METHODS: A total of 30 patients with stable ischemic heart disease were prospectively included. Each underwent CMRI twice and ventriculography. Left ventricular end diastolic volume (EDV), end systolic volume (ESV) and LV ejection fraction (EF) were calculated by two radiologists at different level of experience. Intraobserver, interobserver and interstudy variabilities were assessed. RESULTS: The cut off values were: intraobserver variability (EDV, ESV, EF): 9.4 ml, 5.3 ml, 3.3% for well-trained radiologist; 13.1 ml, 7.5 ml, 4.1% for less-trained radiologist. interobserver variability: EDV: 11.7 and 10.4 ml; ESV: 7.0 and 6.6 ml; EF: 3.9 and 4.2%. interstudy variability (EDV, ESV, EF): 11.6 and 12.6 ml, 7.1 and 7.4 ml, 3.9 and 3.5%, for experienced and less-trained observers. Statistical differences were found between CMRI and ventriculography: CMRI underestimation of EDV and EF, overestimation of ESV. CONCLUSIONS: CMRI volumetric quantification of LV volumes and function is highly reproducible at different levels of experience, but not interchangeable with those obtained by ventriculography.

Impact of rapid enterovirus molecular diagnosis on the management of infants, children, and adults with aseptic meningitis.

Enteroviruses (EV) are the main etiological agents of aseptic meningitis. Diagnosis is made by detecting the genome using RT-PCR. The aim of the study was to evaluate the impact of a positive diagnosis on the management of infants, children, and adults. During 2005, 442 patients were admitted to hospital with suspected meningitis. Clinical and laboratory data and initial treatment were recorded for all patients with enteroviral meningitis. The turnaround time of tests and the length of hospital stay were analyzed. The results showed that EV-PCR detected EV in 69 patients (16%), 23% (16/69) were adults. About 18% of CSF samples had no pleocytosis. After positive PCR results, 63% of children were discharged immediately (mean 2 hr 30 min) and 95% within 24 hr. Infants and adults were discharged later (after 1.8 and 2 days, respectively). The use of antibiotics was significantly lower in children than in infants and adults. The PCR results allowed discontinuation of antibiotics in 50-60% of all patients treated. Patients received acyclovir in 16% of cases (7% children vs. 50% adults) and 23% (11% vs. 69%) underwent a CT scan. Clinical data were compared between patients whose positive EV-PCR results were available within 24 hr (n = 32) and those whose results were available > 24 hr after collection of CSF (n = 14). Duration of antibiotic treatment (difference: 2.3 days; P = 0.05) was reduced between the two groups. No statistical difference in the length of stay was observed. The EV-PCR assay should be performed daily in hospital laboratory practice and considered as part of the initial management of meningitis.

The epidemiology and virology of hepatitis C virus genotype 5 in central France.

BACKGROUND: We previously reported high prevalence of hepatitis C virus genotype 5a (HCV 5) (14%) in Central France. AIM: To identify the risk factors associated with HCV5 infection and to characterize local HCV5 lineages. METHOD: A case-control study and phylogenetic analysis were conducted. RESULTS: In all, 131 HCV5 and 343 HCV non 5 infected patients were enrolled. No HCV5 patient was born in sub-Saharan Africa and only two were injection drug user. HCV5 contamination was associated with living in a rural area called Vic le Comte (VLC) in non-transfused patients (OR = 17.7), with transfusion in patients living outside VLC (OR = 3.8) and with receiving injections in patients from VLC (OR = 3.1). More than 80% of the patients from outside VLC were contaminated by transfusion and those from VLC mainly by an iatrogenic factor - injections performed before 1972 by the local physician. Phylogenetic analysis of HCV5 isolates evidenced no distinct genetic cluster, but close relationships between the isolates of spouse pairs and between blood donors and recipients. CONCLUSIONS: Our results suggest that HCV5 spread in our district by iatrogenic route before 1972 and then via transfusion to the whole district. Collaborative studies are underway to study viral sequences from different parts of Africa and Europe to estimate the origin of our HCV 5a strains.

[Breech presentation and vaginal delivery: evolution of acceptability by obstetricians and patients]. / Accouchement du siège par voie vaginale: évolution de l'acceptabilité par les obstétriciens et les patientes.

OBJECTIVE: To investigate the influence of obstetrician and patient respectively on mode of delivery in case of breech presentation at term. PATIENTS AND METHODS: This retrospective study included all women with a singleton pregnancy in a breech presentation delivered at term in a tertiary care maternity unit from January 1998 to December 2004. Mode of delivery was suggested by a score based on maternal age, parity, obstetrical past history, radiopelvimetry and cephalopelvic confrontation. The obstetrician was free to follow or not the score indication and patient's informed consent was required concerning the mode of delivery. Our main outcome measurements were mode of delivery and neonatal parameters. RESULTS: Two hundred cases were identified. Elective cesarean section increased progressively (from 52% in 1998 to 80% in 2004 [P=0,002]). Neonatal status and proportion of score in favour of vaginal birth remained stable during the study period. The rise in cesarean section rate was mainly due to patient's request (P=0,001) whereas the trend of obstetrician in favour of cesarean did not reach significance (P=0,3). DISCUSSION AND CONCLUSION: The rise of elective cesarean section for term breech delivery in a maternity unit using a predefinite score is mainly induced by patient's request. This evolution has no effect on neonatal status.

[Regression in primary cutaneous melanoma is not predictive for sentinel lymph node micrometastasis]. / Absence de valeur prédictive des signes de régression histologique sur l'envahissement du ganglion sentinelle.

BACKGROUND: The predictive value of regression in melanoma is debated. AIM OF THE STUDY: A retrospective single-centre study to evaluate the correlation between regression in primary skin tumor and the presence of micrometastases in sentinel lymph nodes. PATIENTS AND METHODS: Histological signs of regression in 84 melanomas (>1 mm) with corresponding sentinel lymph nodes were studied by two independent pathologists. RESULTS: Regression was seen in 40 skin melanoma tumors while micrometastasis was seen in 24. Of the tumors with micrometastasis, only 10 were regressive (RR: 0.47, p=0.49). Breslow value>2 mm and male sex were predictive for node micrometastasis (RR: 4.6, p=0.03 and RR: 7.6, p=0.006, respectively). On multivariate analysis, these two factors were independent. COMMENTS: These data suggest that regression in primary cutaneous melanoma is not predictive for lymph node metastasis.

Prenatal detection and outcome of congenital diaphragmatic hernia: a French registry-based study.

OBJECTIVES: To describe the true incidence, prenatal detection rate and fetal outcome of congenital diaphragmatic hernia (CDH) in a systematically registered population over an 18-year period and to determine any change in trends over time. METHODS: This was a retrospective study of all cases of CDH registered in the Central-Eastern France Birth Defects Registry from 1986 to 2003. All fetuses and infants up to 1 year of age diagnosed with CDH were registered, including miscarriages later than 22 weeks of gestation, stillbirths and terminations of pregnancy (TOP). Routine prenatal screening consisted of three ultrasound examinations and there was no upper limit of gestational age for TOP. RESULTS: Five hundred and one cases of CDH were identified from a total of 1 835 022 live births (2.7 cases per 10 000 live births). The overall prenatal detection rate was 54%. There was a significant increase over time in the detection rate mainly for associated CDH and left-sided CDH (P < 0.0001), and in the proportion of neonates delivered in tertiary centers (P < 0.0001). The overall survival rate at discharge was 47% and this increased significantly over time for isolated CDH (P = 0.04), whereas it was lower and remained stable for associated CDH (P = 0.64). The TOP rate for isolated CDH did not vary significantly in contrast to that for associated CDH cases in which the TOP rate increased over time, progressively replacing the neonatal death rate (P = 0.01). CONCLUSIONS: Over an 18-year period, this large population-based study demonstrated increasing prenatal detection rates for associated CDH and left-sided CDH and confirmed an increasing survival rate mainly for isolated CDH.

Peginterferon alpha-2b plus ribavirin for treatment of chronic hepatitis C with severe fibrosis: a multicentre randomized controlled trial comparing two doses of peginterferon alpha-2b.

We compared sustained virological response (SVR) in chronic hepatitis C patients with severe fibrosis treated with pegylated interferon (Peg-IFN) alpha-2b 1.5 microg/kg/week or 0.75 microg/kg/week in combination with ribavirin 800 mg/day for 48 weeks. This was a multicentre randomized controlled study. SVR was observed in 44.5% (45/101) of patients treated with the standard dose of Peg-IFN and 37.2% (38/102) of patients treated with the low dose (NS). In patients with genotypes 1, 4 and 5, SVR was observed in 25.0% of patients who received the standard dose and 16.9% of patients who received the low dose of Peg-IFN (P = NS). In patients with genotypes 1, 4 and 5 and low viraemia, SVR was obtained in 27.3% of patients treated with the standard dose and 25.8% of patients treated with the low dose (P = NS). In the high-viraemia subgroup, SVR was obtained in 24.0% and 9.1% of patients, respectively. In patients with genotypes 2 and 3, SVR was similar in both groups (73.2%vs 73.0%). Thus, (1) patients with genotypes 2 and 3 and severe fibrosis can be treated with low dose of Peg-IFN and ribavirin, (2) this study suggests that patients with genotypes 1, 4 and 5 and high viraemia could receive a standard dose of Peg-IFN associated with ribavirin for 48 weeks, (3) side effects limit the efficacy of the treatment with standard dose of Peg-IFN in patients with genotypes 1, 4 and 5 and low viraemia, (4) more studies are needed for patients with genotype 2 or 3 to define the optimal duration (24 or 48 weeks) in patients with severe fibrosis.

Effectiveness of interferon plus ribavirin combination in the treatment of naive patients with hepatitis C virus type 5. A French multicentre retrospective study.

AIM: To assess the rate of sustained virological response in naïve hepatitis C virus-type 5 patients treated by standard interferon or pegylated-interferon [corrected] (peg-interferon) and ribavirin combination for 48 weeks. PATIENTS AND METHODS: A total of 87 hepatitis C virus patients were included from 12 centres in France; 28 patients received interferon plus ribavirin and 59 were treated with peg-interferon plus ribavirin. RESULTS: Baseline characteristics were: mean age 58 +/- 11 years, sex ratio 1, 66% had metavir fibrosis score >or=F2, 21% were cirrhotics and 53% had pretherapeutic viral load >or=800,000 IU/mL. Sustained virological response was achieved in 64% and 58% of hepatitis C virus-5 patients treated with interferon and peg-interferon, respectively (NS). In adherent patients, sustained virological response was obtained in 75% of patients. Sustained virological response in hepatitis C virus-5 patients (60%) was significantly higher than sustained virological response in hepatitis C virus-1 patients (37%) (P = 0.0499) and not significantly different from sustained virological response in hepatitis C virus-2-3 patients (63%) (P = 0.8098). CONCLUSIONS: Combination therapy is effective in 60% of hepatitis C virus-5-infected patients. Sustained virological response seems better in hepatitis C virus-5 patients than in hepatitis C virus-1 patients, and is similar to that of hepatitis C virus-2-3 patients. More studies are needed to determine optimal duration of treatment in hepatitis C virus-5 patients.

[Rapid diagnosis of rotavirus infections: comparative prospective study of two techniques for antigen detection in stool]. / Diagnostic rapide des infections à rotavirus: étude prospective comparative de deux techniques de détection d'antigènes dans les selles.

The ability of two commercially available diagnosis rapid assays in detecting rotavirus antigen was compared in a prospective study conducted from September 2002 to May 2003. Five hundred and twelve faecal specimens were studied by IDEIA Rotavirus enzyme immunoassay test (EIA) and Diarlex MB immunochromatographic test (ICG). Specimens giving discrepant results were examined by electron microscopy (EM) and clinical data reconsidered. Out of 512 stool specimens, 155 (30.3%) were positive and 332 (64.8%) negative with the two assays. Discrepant results were obtained for 25 (4.88%) specimens (24 children, 1 adult), with EIA giving more positive results. The retrospective examination by EM, possible for fifteen stools on the 25 that gave discrepant results, confirmed the presence of rotavirus in 7/14 stools which were positive only by EIA and in the stool specimen that was found positive only by ICG. The 25 clinical observations re-examination showed the presence of GEA signs in all cases. The statistical analysis shows an excellent concordance between the EIA and the ICG tests (kappa = 0.89, IC(95%) = [0.85-0.93]) in spite of the underestimation of ICG test in comparison with EIA test (P < 0.0001).

[Neonatal morbidity after conservative management followed by systematic delivery at thirty-four weeks of gestation in preterm rupture of membranes]. / Morbidité néonatale après attitude d'expectative suivie d'une naissance systématique à 34 semaines d'aménorrhée en situation de rupture prématurée des membranes.

OBJECTIVE: To evaluate the neonatal morbidity and its risks factors in case of uncomplicated preterm rupture of membranes managed conservatively with subsequent planned delivery at 34 weeks of gestation. PATIENTS AND METHODS: We studied retrospectively 42 consecutive neonates systematically delivered at 34 weeks of gestation after more than 48 hours of conservative management for uncomplicated preterm rupture of membranes. Conservative management was conducted in a single tertiary care center and consisted in corticotherapy and in antibiotherapy (amoxycilline during 7 days). We evaluated the neonatal mortality rate, the incidence of infection, respiratory distress, neurological disorders, and we looked for their prenatal risks factors. RESULTS: Forty-two neonates were included. The median gestational age at rupture was 31.1 weeks of gestation (from 25 to 33.9 weeks). The median duration of expectant management was 20 days (from 2.4 to 65 days). We observed 7 cases of neonatal infection but no septic failure, 18 cases of respiratory distresses among which 9 required a tracheal intubation for a mean duration of 3.7 days, no perinatal encephalopathy (5 cases of subependymal haemorrhage) and no neonatal death. We isolated one single risk factor that was the lowest gestational age at rupture in case of subsequent respiratory distress (29.6 vs 31.9 weeks; P=0.02). DISCUSSION AND CONCLUSION: Neonatal morbidity in this population consisted mainly in respiratory distresses with an increased incidence when gestational age at rupture decreased.

[Obstetrical prognosis of labour induction with mifepristone after 41 weeks of gestation]. / Pronostic obstétrical du déclenchement artificiel du travail au-delà de 41 semaines d'aménorrhée en fonction de la réponse à la mifépristone.

OBJECTIVE: To compare the mode of delivery in two groups of patients selected by their response after induction of labour with mifepristone. PATIENTS AND METHODS: We studied retrospectively 89 cases of labour induction with viable children after 41 weeks of gestation. Bishop scores were less than 6. Patients were given 200 mg of mifepristone per day for 48 h. They were retrospectively divided into group 1 (spontaneous onset of labour or premature rupture of membranes before the third day) and group 2 (not in labour by that date). RESULTS: The mean Bishop score at inclusion was 3.1 +/- 1.3. Among the 51 patients (53.9%) in group 1, one required prostaglandins and we performed 10 cesarean sections. In group 2, the mean Bishop score at the 3rd day was 4.4 +/- 1.3 (P < 0.0001). Twenty-four patients required prostaglandins (P < 0.0001) and we performed 17 cesarean sections (P = 0.01). The number of cesarean sections increased with the dose of prostaglandins (P = 0.025). We observed no maternal or fetal complications. DISCUSSION AND CONCLUSIONS: Mifepristone was successful in inducing labour spontaneously in over 50% of pregnancies after 41 weeks of gestation. In the other group, the probability of vaginal delivery was reduced especially when high doses of prostaglandins were required. After the use of mifepristone, we suggest to shorten the duration of prostaglandin administration (two applications of 2 mg dinoprostone) before performing cesarean section.

[Outcome of hyperlactatemia and lipodystrophy syndromes in patients infected with human immunodeficiency virus]. / Survenue des syndromes lipodystrophiques et hyperlactatémiques chez des patients infectés par le virus de l'immunodéficience humaine.

HIV-positive persons requiring a highly active antiretroviral therapy containing one or more nucleosidic reverse transcriptase inhibitors associated with or without protease inhibitors are exposed to metabolic side effects among which lipodystrophy and hyperlactemia, defined by blood lactates higher than 2,25 mmol/L. Hyperlactatemia had to be differentiated from lactic acidosis of type B (without hypoxemia, lactates higher than 5 mmol/L and arterial pH lower than 7,3), a rare but potentially fatal complication by multi-visceral failure. The accused INRT induce mitochondrial toxicity by inhibition of DNA gamma polymerase and deterioration of its DNA. Our exploratory study, troop of 282 patients, identified age and stavudine like statistically associated, which has occurred of this metabolic anomaly. The patients having profited of a therapeutic change with the profit from drugs minus hyperlactatogenic presented an obvious clinical and biological improvement; whereas similar switch of therapy occurred for the lipodystrophic patients presented any clinical improvement. Nevertheless, biological parameters (blood lactates, triglycerides, total cholesterol and LDL-cholesterol) were significantly decreased after this therapeutic switch occurred on the lipodystrophic patients. In conclusion, the measurement of the following biological parameters: glycemia, lactatemia, triglycerides, total cholesterol and LDL-cholesterol at patient VIH, in a simple and rigorous pre-analytical and analytical context, appears to us justified in the monitoring of metabolic disorders in treated HIV patients by INRT and/or IP.

The effect of genotype on the natural history of eIF2B-related leukodystrophies.

BACKGROUND: Recessive mutations in the five eucaryotic initiation factor 2B (eIF2B) subunits have been found in leukodystrophies of variable age at onset and severity. OBJECTIVES: To evaluate the clinical spectrum of eIF2B-related disorders and search for a phenotype-genotype correlation. METHODS: Ninety-three individuals (78 families) with an undetermined leukodystrophy were selected on MRI-based criteria of childhood ataxia with central hypomyelination/vanishing white matter (CACH/VWM) for EIF2B genes analysis. RESULTS: Eighty-nine percent of individuals with MRI criteria of CACH/VWM have a mutation in one of the eIF2B beta to epsilon subunits. For 83 individuals (68 families), 46 distinct mutations (90% missense) in four of the five eIF2B subunits (beta, gamma, delta, epsilon) were identified. Sixty-four percent were in the epsilon subunit, a R113H substitution was found in 71% of eIF2B epsilon-mutated families. A large clinical spectrum was observed from rapidly fatal infantile to asymptomatic adult forms. Disease severity was correlated with age at onset (p < 0.0001) but not with the type of the mutated subunit nor with the position of the mutation within the protein. Mutations R113H in the epsilon subunit and E213G in the beta subunit were significantly associated with milder forms. CONCLUSIONS: The degree of eIF2B dysfunction, which is involved in the regulation of protein synthesis during cellular stress, may play a role in the clinical expression of eIF2B-related disorders.