Genotype-phenotype correlations in fetuses and neonates with autosomal recessive polycystic kidney disease.

The prognosis of autosomal recessive polycystic kidney disease is known to correlate with genotype. The presence of two truncating mutations in the PKHD1 gene encoding the fibrocystin protein is associated with neonatal death while patients who survive have at least one missense mutation. To determine relationships between genotype and renal and hepatic abnormalities we correlated the severity of renal and hepatic histological lesions to the type of PKHD1 mutations in 54 fetuses (medical pregnancy termination) and 20 neonates who died shortly after birth. Within this cohort, 55.5% of the mutations truncated fibrocystin. The severity of cortical collecting duct dilatations, cortical tubule and glomerular lesions, and renal cortical and hepatic portal fibrosis increased with gestational age. Severe genotypes, defined by two truncating mutations, were more frequent in patients of less than 30 weeks gestation compared to older fetuses and neonates. When adjusted to gestational age, the extension of collecting duct dilatation into the cortex and cortical tubule lesions, but not portal fibrosis, was more prevalent in patients with severe than in those with a non-severe genotype. Our results show the presence of two truncating mutations of the PKHD1 gene is associated with the most severe renal forms of prenatally detected autosomal recessive polycystic kidney disease. Their absence, however, does not guarantee survival to the neonatal period.

Morphological features of the human umbilical vein in normal, sickle cell trait, and sickle cell disease pregnancies.

Pathological changes often occur in the placenta of women with sickle cell disease (SCD). These alterations are caused by sickling of erythrocytes and vasoocclusion in the placental circulation, leading to regional hypoxia. However, the morphological status of the umbilical cord, which is in close physical association with the placenta, is not documented under such conditions. To explore this, the umbilical vein structure in healthy, sickle cell trait (the heterozygous state), and SCD pregnancies was studied using scanning (SEM) and transmission electron microscopy (TEM). Interestingly, the sickle cell trait umbilical vein architecture was morphologically similar to that in control veins, whereas numerous alterations were seen in the SCD umbilical vein wall. In SEM, the SCD umbilical vein endothelial cells showed atypical morphologies. TEM analysis of the tunica media showed (1) smooth muscle cell proliferation and increase in the thickness of the basement membrane underlying the cells; (2) areas of necrosis; (3) reduplication of the inner elastic lamina. Such features were often seen in sickle patients vasculature at autopsy. Our findings could have importance because tissue hypoxemia is an integral part of vasoocclusion. We conclude that the SCD umbilical vein may be an additional tool for studying vasoocclusion in sickle cell disease.

The Guadeloupean perinatal mortality audit: process, results, and implications.

In 1983, we implemented an ongoing perinatal mortality audit in Guadeloupe to identify factors underlying the current level of poor perinatal outcome and to stimulate increased provider motivation. The audit was part of an active research approach to document the specific nature of the perceived perinatal health problem, to modify provider behavior through the use of this acquired information, and, ultimately, to decrease avoidable perinatal deaths. We investigated all 320 perinatal deaths in Guadeloupe during 1984 and 1985. Nearly one-half of the perinatal deaths reviewed were determined to be related to maternal high blood pressure, maternal/fetal infection, and preterm delivery. Slightly more than one-half of the perinatal deaths were considered to be avoidable. Over the course of the audit, perinatal mortality rates exhibited a marked decline. The findings of this study support claims that perinatal audits with confidential inquiries may help effect change in perinatal health status in a population; the findings also call attention to the potential benefits of incorporating motivational incentives into these activities.

PIP: In 1983, the authors implemented an ongoing perinatal mortality audit in Guadeloupe to identify factors underlying the current level of poor perinatal outcome and to stimulate increased provider motivation. The audit was part of an active research approach to document the specific nature of the perceived perinatal health problem, to modify provider behavior through the use of this acquired information, and, ultimately, to decrease avoidable perinatal deaths. The authors investigated all 320 perinatal deaths in Guadeloupe during 1984-85. Nearly 1/2 of all perinatal deaths reviewed were determined to be related to maternal high blood pressure, maternal/fetal infection, and preterm delivery. Slightly more than 1/2 of the perinatal mortality rates exhibited a marked decline. The findings of this study support claims that perinatal audits with confidential inquiries may help effect change in perinatal health status in a population; the findings also call attention to the potential benefits of incorporating motivational incentives into these activities.

Prenatal transmission of dengue: two new cases.

Dengue is commonly observed in most tropical countries, but its transmission from mother to fetus has not been frequently described. We report two such cases. The first signs of dengue in the infants appeared on the 3rd and 9th days of life. In both, a bacterial infection was suspected initially. In areas where it is endemic, the diagnosis of dengue should be considered in the neonate with signs of bacterial infection. When dengue is suspected in a pregnant woman, laboratory investigation and extended observation of the newborn are advised.

Anamnestic pregnancy risk assessment.

Based on data obtained from the 1984-1985 Guadeloupean Perinatal Audit, a pregnancy risk scoring system was developed using maternal demographic, socioeconomic, obstetric history and risk characteristics recorded at the first prenatal visit. Various combinations of risk factors were identified for four distinct pregnancy outcomes (perinatal mortality, low birth weight, preterm delivery and intra-uterine growth retardation). The findings emphasize the importance of developing risk assessments for discrete pregnancy outcomes within specific populations.

Efficiency of prenatal counselling for sickle cell disease in Guadeloupe.

As in most caribbean countries, Sickle Cell Disease (SCD) is a major public health problem in Guadeloupe. A prenatal counselling program was developed, at an early stage of pregnancy, for at-risk couples. Over a 6 year period, 144 couples at-risk of having a child with homozygous sickle cell (SS: n = 103) or sickle cell C disease (SC: n = 41) were seen for prenatal counselling. Among those belonging to the SS risk group, 64 (62%) underwent prenatal diagnosis (PND), which allowed identification of 27 SS fetuses, with an induced abortion rate of 70%. Among those of the SC risk group, 14 (34%) accepted PND and the diagnosis of SC was made in 5 cases with an induced abortion rate of 60%. Factors, appeared to play a role in seeking PND and induced abortion, were the type of risk (SS or SC), multiparity, existence of affected child in the family and gestational age at the time of counselling. Our experience reveals that, an early prospective identification of at-risk couples combined with education to increase the awareness of the problem at the individual and population level need to be achieved to further improve the efficiency of our prevention program.

[Acute childhood gastroenteritis study at Central University Hospital of Pointe-à-Pitre/Abymes, Guadeloupe, from November 1997 to March 1998]. / Enquête sur les gastro-entérites aiguës infantiles au CHU de Pointe-à-Pitre/Abymes, Guadeloupe, de novembre 1997 à mars 1998.

To determine the role of enteric pathogens in acute childhood diarrhoea in Guadeloupe, 161 children (108 cases and 53 controls) from 0 to 2 years of age, admitted to Pointe-à-Pitre/Abymes University Hospital, were evaluated over a five-month period. A known enteric pathogen was identified in 40.8% of children. The most commonly identified aetiologic agents were Salmonella (16.7% of cases), especially Haddar serotype and Rotavirus (20.5%). This virus was isolated more often in the dry season. Adenovirus were detected in 3.6% of diarrhoeal stools and were not significatively associated with diarrhoeal disease. No Shigella, Campylobacter or parasites were found.

[Analysis of hospitalization of adult sickle-cell patients in Guadeloupe]. / Analyse des hospitalisations chez les patients drépanocytaires adultes en Guadeloupe.

PURPOSE: To determine the characteristics of acute hospitalizations in adult patient with sickle-cell disease in Guadeloupe. METHODS: We retrospectively studied clinical features of adult patients followed up by the "Centre Caribeen de la Drépanocytose" (CCD) in 1996. Data were collected from the medical records of the hospitalized patients and the longitudinal records of the CCD. RESULTS: Sixty-three (25%) of the 251 patients who were followed up by the CCD required hospitalization in 87 cases (1.38 hospitalizations/patient). Mean age of the hospitalized patients was 27.5 years (range 17 to 71 years). Most hospitalizations involved men (29 [31%] vs 34 [22%] for women, P < 0.05), and most were for homozygous patients with sickle-cell anemia: 39 (31%) SS, 19 (18.55%) SC and five (21.75%) S beta thal. A painful vaso-occlusive crisis was noted in 67 episodes. There were nine acute chest syndromes (ACS), six of them occurred following a vaso-occlusive crisis. We noted 39 infectious episodes. The increase in C-reactive protein (> 100 mg/L) was associated with ACS or urinary infection. A patient with renal failure died during septicemia. CONCLUSION: This study confirms the need for prevention of painful crises and other severe complications in patients with sickle-cell disease.

[An example of research and actions related to perinatal mortality in Guadeloupe. Factors and profiles of sociodemographic risk]. / Un exemple de recherche-action sur la mortalité périnatale en Guadeloupe. II. Facteurs et profils de risque socio-démographiques.

Perinatal risk factors in Guadeloupe (French West Indies) have been analysed from a community-based case-control survey. Two hundred and sixty four perinatal deaths were involved along with 605 controls. Principal component factor analysis of individual risk characteristics was used to identify risk group profiles. These risk profiles were: "single women of low socio-economical status" (17% of the variability), "traditional Caribbean housewives" (14%), "single adolescents" (7%), and "immigrant women" (10%). Only the three first were significantly associated with a poor outcome for the current pregnancy. This approach may be fruitful in planning for public health interventions to prevent perinatal risk. Also, risk profile concepts may be well-accepted by physicians and care providers, in routine practice, for screening of individual at-risk patients.

[An example of the effect of research on perinatal mortality in Guadeloupe (1984-1985). I. Objectives and methodology]. / Un exemple de recherche-action sur la mortalité périnatale en Guadeloupe (1984-1985). I. Objectifs et méthodologie.

Research with a view to action being taken was carried out in Guadeloupe in 1984 and 1985 to try to find out the causes of the high level of perinatal mortality which persists on the island before suggesting to the public health authorities what action to take. All the cases of perinatal mortality (above 500 g in weight) were looked at and analysed carefully according to a protocol that had been prepared. The events preceding the perinatal death were described and also the antenatal and intranatal as well as immediate post-natal care given to the children. A control case was studied for each case that had been registered and the same questionnaire was filled in. The present work shows the methodology used to carry out the enquiry and how it was organized with the collaboration of all the actors in the public health department as well as the doctors and the health authorities authorities.

[Sickle cell anemia and pregnancy: review of 68 cases in Guadeloupe]. / Drépanocytose et grossesse: revue de 68 observations en Guadeloupe.

Pregnancy in women with major sickle cell syndromes is a high risk maternofetal situation. This descriptive study presents the features and the clinical course of 68 pregnancies in sickle cell women who were delivered in Guadeloupe from January 1(st) 1993 to December 31(st) 1997. Specific complications were observed in all hemoglobin types, but with a severer course in SS women. Painful vaso-occlusive crises were the main causes of hospitalisation (88% of SS pregnancies and 27% of SC pregnancies) associated most often with worsening anemia and / or infection. Acute chest syndrome was observed in all genotypes at any time throughout pregnancy and during the post partum period. One death occurred (a 16 years old SBeta(+)thal woman). Fetal mortality and morbidity were also high, intrauterine growth retardation and fetal death being the most frequent fetal complications. The rates of prematurity (21%) and caesarean section (48%) were higher than in the whole population. Three (3) neonatal deaths occurred. A multidisciplinary and specific approach, vigilance of health care providers and patient compliance are required to manage efficiently pregnancy, delivery and post partum in sickle cell women.

[Conditions of use and access to care of sickle cell anemia patients. Analysis of the literature]. / Conditions d'usage et d'accès aux soins des drépanocytaires. Analyse de la littérature.

In order to identify the care access and life conditions and non-compliance risk factors of sickle-cell patients, we performed a literature survey on these subjects, and on other chronic pathologies and care systems used as references. The data showed a positive influence of good quality of life, social support and family environment on diabetes mellitus patients compliance, and the negative effect of poor socioeconomic status on adequate prenatal care. Concerning sickle-cell disease, there were few data on the non-compliance risk factors. However, the authors identified factors which influence the patient health status and showed the negative result of the disease on the quality of life of the patient and his family. A new study has been induced by these conclusions on the sickle-cell disease cohort of Guadeloupe reference center.

[Natural history of sickle cell anemia]. / Histoire naturelle de la drépanocytose.

Sickle-cell anaemia is characterized by three categories of clinical signs: anaemia, vaso-occlusive phenomena and infective complications, which are described here according to age. The natural history of the disease can be divided into four periods: the neonatal period which is asymptomatic but important to organize an effective protection; the first 5 years of life are characterized by a high risk of mortality, a high level of morbidity due to severe infections, episodes of acute anaemia and painful crises typical of that age-group; the life of older children and adolescents is dotted with painful crises; it is in this period that degenerative tissue pathology begins; in adulthood, the acute episodes are less frequent, but multiple complications develop. Some of them (cerebral vascular accidents or lung diseases) may be fatal, while others are the source of chronic and disabling lesions, notably ocular, orthopaedic and renal lesions, which affect the functional prognosis. Pregnancy remains a high risk. There is, therefore, a striking contrast between the basic physiopathological mechanism (polymerization of haemoglobin S) and the various clinical manifestations which depend on the type of haemoglobin, on the social and sanitary conditions in each country and on other reasons which remain to be elucidated.

[XY/XO mosaicism in a child with feminime phenotype manifesting internal genital ambiguity]. / Mosaique xy/xo chez un sujet de phénotype féminin présentant une amgiguite génitale interne.

A 18 year old patient presented with a female phenotype and no signs of sexual maturation. The leukocyte karyotype was XY. At laparotomy, there was no uterus and the gonadal streaks had a XY/XO mosaicism. There were rudiments of fallopian tubes and epididymis. Histologic examination of the gonads showed foci of Leydig and Sertoli cells.

Sickle cell disorder, beta-globin gene cluster haplotypes and alpha-thalassemia in neonates and adults from Guadeloupe.

We have studied haplotype of beta(S) chromosome and alpha-globin gene status in 534 patients (255 adults and 279 children of whom 159 neonates) from Guadeloupe with various sickle cell-related conditions, namely SS (n = 298), SC (n = 170), S-beta-thal (n = 56), and other rare forms (n = 10). Haplotype data on beta(S) chromosomes confirm our previous observation that Benin type is the most prevalent (75%) beta(S) chromosome in Guadeloupe, in disagreement with the historical records. Comparison of the frequency of distribution of various beta(S) haplotypes between neonates and adults on the one hand and between SS and SC cases on the other shows that the current beta(S) haplotype distribution in this island is not distorted by haplotype-related differential survival. We also show that the frequency of alpha-thalassemia (-3.7 kb) in Guadeloupe is one of the highest recorded in this region involved in Atlantic slave trade and also failed to reveal any age-dependent increase in frequency. We conclude that the African component of Guadeloupe is distinct from that of Brazil and Cuba but is close to that of Jamaica.

beta S haplotypes, alpha-globin gene status, and hematological data of sickle cell disease patients in Guadeloupe (F.W.I.).

The beta gene cluster haplotypes, alpha gene status, Hb F level and hematological parameters have been characterized in 154 unrelated Guadeloupe patients with sickle cell disease: 112 with sickle cell anemia, 26 with SC disease, 15 with Hb S-beta-thalassemia, and one patient with Hb S in association with the hereditary persistence of fetal hemoglobin. Fourteen haplotypes in 16 combinations were found, the three major African haplotypes were present on 92% of all chromosomes: 73% Benin, 11% Bantu, 8% Senegal. Among SS patients, 57% were Benin homozygotes, one patient was a Senegal homozygote, one patient was a Bantu homozygote, and all the others were heterozygous. The A gamma T chain was observed on seven chromosomes and about 5% of the analyzed beta S chromosomes exhibited atypical haplotypes. The common haplotype beta C was found in all patients with SC disease. An interesting feature was the high frequency (44%) of deletional alpha-thalassemia among SS patients. Two patients have an alpha-gene globin triplication. The DNA haplotypes and alpha-gene status have been correlated with hematological parameters in these patients. The anthropological aspect of these data is interesting as the haplotypes of the beta-globin gene throw light on the slave trade from the various parts of Africa to the Caribbean Islands in particular, and North America in general.

Prevalence of fragile-X syndrome and FRAXE among children with intellectual disability in a Caribbean island, Guadeloupe, French West Indies.

Fragile-X syndrome (FXS) is the most common cause of inherited intellectual disability. Although FXS has been identified in all the main ethnic groups, little is known about its prevalence with respect to ethnicity. Since the identification of the FXS primary defect, diagnosis involving DNA analysis has been made possible, allowing efficient screening strategies to be considered. The present authors have carried out FXS screening among children belonging mainly to the Afro-Caribbean ethnic group (163 boys and 85 girls) affected with moderate to severe intellectual disability of previously unknown origin. We have found a 6.7% and 0% prevalence among boys and girls, respectively, yielding a minimum FXS incidence of 0.42 per 1000 male births per year. Family studies have resulted in genetic counselling for several individuals. FRAXE screening was also achieved and no FRAXE case was detected in this study.