Rapid differential diagnosis of diabetes insipidus in a 7-month-old infant: The copeptin approach.

INTRODUCTION: Diabetes insipidus is characterized by hypoosmotic polyuria related to deficiency of arginine-vasopressin (AVP) secretion (central diabetes insipidus, CDI) or renal insensitivity to AVP (nephrogenic diabetes insipidus, NDI). The water deprivation test with assessment of AVP activity is currently the gold standard for differential diagnosis in patients presenting polyuria-polydipsia syndrome. Nevertheless, it can be dangerous without proper surveillance and its interpretation may be challenging. Other markers have been suggested. Direct quantification of circulating AVP is not sufficient for diagnosis: vasopressin is unstable, analysis is complex. AVP comes from prohormone preprovasopressin with concomitant release of copeptin (C-terminal moiety) in the equimolar ratio. Copeptin is stable in vitro, with easy and rapid measurement (<4h). Past studies have shown greater sensitivity and specificity of copeptin versus AVP to discriminate etiologies of polyuria in adults, but its value has not been demonstrated in infants yet. OBSERVATION: A 7-month-old infant presented polyuria-polydipsia syndrome with poor weight gain. Laboratory tests pointed out hypernatremia (170mmol/L) and blood hyperosmolarity (330mOsm/L) with inappropriate urinary hypoosmolarity (168mOsm/L). Plasmatic copeptin measurement was found at a very high level, 303pmol/L (1-14pmol/L). DdAVP administration did not improve the polyuria, confirming the final diagnosis of NDI. Hyperhydration with a hypoosmolar diet normalized the hydration status and circulating levels of copeptin within 1 week. CONCLUSION: Copeptin, a stable peptide reflecting AVP secretion, could be a safer and faster biomarker for etiological diagnosis of polyuria-polydipsia syndrome in children. Before regularization of hydration status, a single baseline measurement may be enough to discriminate NDI from other etiologies without the water deprivation test.

[Neonatal presentation of Prader-Willi syndrome: A report of five cases]. / Présentation néonatale du syndrome de Prader-Willi : à propos de 5 cas.

Prader-Willi syndrome (PWS) is a fingerprint disease caused by the loss of paternally inherited chromosome 15q11.2-q13. In several populations studied, prevalence is estimated to be from 1/10,000 to 1/25,000 births. The disease initially manifests by neonatal hypotonia associated with orality disorders. Secondly, hyperphagia appears with significant obesity and hypogonadism. Motor milestones and language development are delayed, and all individuals have variable degrees of cognitive disability during childhood. Frequently, the most prominent features do not become evident until the later childhood stage, which can lead to underdiagnosis or late diagnosis in early childhood. Because of the long-term implications of this syndrome, it is important to recognize its features as soon as possible so that early counseling of parents and the affected child is possible. The diagnosis is suspected on clinical grounds and confirmed by genetic analysis. Prenatal diagnosis is possible and can be considered in polyhydramnios, decreased fetal active movements, malpresentation, oddly positioned hands and feet, and abnormal fetal heart rhythm. Since PWS can also lead to complications in both pregnancy and labor, proper prenatal diagnosis can also help optimize perinatal care for affected children. We report a series of five newborns for whom PWS was diagnosed in the neonatal period over 6 years. During this period, no prenatal signs of PWS were detected. The incidence in our population was 1/7937 births. The disease was diagnosed on clinical criteria: severe hypotonia, failure to thrive with poor sucking, and dysmorphic and abnormalities of the genitalia. Polyhydramnios was observed in only one case. The delivery was normal for only one patient. All except one were term newborns. There were three males and two females. We noted abnormal fetal heart rate for 80 % of the patients. The birth weight was close to the 10th percentile for two patients, less than the 3rd percentile for two others. All individuals had eutrophic cranial perimeter and four presented peculiar position of fingers. Genetic analyses found a deletion of the paternal chromosome 15 in three patients (60 %) and maternal uniparental disomy for the two others (40 %). The distribution by sex, weight, cranial perimeter, and mutations are those reported in the literature. PWS should be sought in cases of severe neonatal hypotonia, most particularly if it combines dysmorphism, hypogonadism, malposition of the fingers, and suggestive prenatal history. An early diagnosis provides better multidisciplinary care for the patient and family. We have no explanation for the higher incidence of the disease than in the general population. It is possible that this incidence is only fortuitous, but further studies would help to identify potential risk factors for the disease.

[Do we need congenital adrenal hyperplasia screening for premature infants?]. / Faut-il maintenir un dépistage de l'hyperplasie congénitale des surrénales pour les prématurés ?

Congenital adrenal hyperplasia neonatal screening has been introduced in France since 1995. A recent survey has questioned its relevance in premature infants because of a high number of false positives and a low positive predictive value of 17-hydroxyprogesterone dosage. A workgroup at the French screening association (Association française de dépistage et de prévention des handicaps de l'enfant) collected all the epidemiological, clinical and biological data of premature children presenting with adrenal hyperplasia from the national cohort. Their results were compared with those of healthy premature children. All the data showed that the screening in children born before 32 weeks of gestational age is irrelevant, but that it is efficient after this term. A pilot study has been implemented in population to evaluate the opportunity to discontinue this screening in extreme preterm neonates.

Comparative multicentre study of the immunogenicity of different hepatitis B vaccines in healthy volunteers.

In a comparative study of the immunogenicity of different hepatitis B vaccines, 339 healthy seronegative adults at three different centres were randomly allocated to receive either three doses of a yeast-derived vaccine at one of three different dose levels (10, 20, or 40 micrograms; SmithKline Biologicals) or one of two commercial plasma-derived vaccines at standard dose levels (5 micrograms, Institut Pasteur Production or 20 micrograms, Merck Sharp & Dohme). The subjects were inoculated intramuscularly in the deltoid region according to a 0, 1, and 6 month schedule. No severe or serious adverse reactions attributed to any of the vaccines were observed. One month after the third vaccine dose, seroconversion rates ranged from 95% to 100% in all groups with only 6 subjects failing to seroconvert. Although there were no statistically significant intra-centre differences in antibody levels, the Tours/Chateauroux groups generally attained higher antibody levels than those from Limoges for the same yeast-derived vaccine dose. This unexplained difference between centres was not found for the plasma-derived vaccines. Older subjects responded less well than younger ones and females attained higher antibody levels than did males. The yeast-derived vaccine is comparable to the two commercially available plasma-derived vaccines in terms of reactogenicity and immunogenicity.

[Prevention of ocular toxicity of ethambutol: study of zincaemia and chromatic analysis (author's transl)]. / Prévention de la toxicité oculaire de l'éthambutol: intérêt de la zincémie et de l'analyse du sens chromatique.

In order to define the means of prevention of the ocular toxicity of ethambutol (EMB), 72 patients under treatment with EMB-INH-Rifampicin combination were subjected to systematic analysis of plasma, blood and urinary zinc levels together with a full ophthalmic examination. Comparison of the results from 12 patients sustaining ocular damage at the time of treatment with the results of 60 others: 1) demonstrates the existence of a correlation between plasma zinc levels before treatment and the probability of ocular damage from EMB (high risk for zinc is less than 0.70 mg/l - almost no risk for zinc greater than 1 mg/l); 2) confirms that dyschromatopsia is one of the first signs of ocular damage through EMB and thus constitutes an alarm signal; 3) suggests that the ocular toxicity of EMB might appear in the retina before the optic nerve.