Severe hyperhomocysteinemia and peripheral neuropathy as side effects of nitrous oxide in two patients with sickle cell disease.

Nitrous oxide (N2O) is a widely used anesthetic agent. We report two patients with sickle cell disease (SCD) who presented with complications following the use of N2O. Patient 1, a 15-year-old girl, presented severe hyperhomocysteinemia, pancytopenia, vitamin B12 deficiency, and peripheral polyneuropathy after massive use of N2O for pain management. At the 1-year follow-up, hyperhomocysteinemia and B12 deficiency had resolved, but she had persisting mild symptoms of polyneuropathy. Patient 2, a 17-year-old boy, presented only severe hyperhomocysteinemia, only partially corrected by initial B12 supplementation. Careful monitoring of N2O use, especially in patients with SCD, is mandatory to prevent complications.

[Type 2N von Willebrand disease (Normandy)]. / La maladie de Willebrand de type 2N "Normandie". À propos d'une observation.

Willebrand disease is the most common constitutional abnormality of hemostasis. It reflects a qualitative or quantitative abnormality of von Willebrand factor (vWF) responsible for hemorrhagic syndrome, mainly mucosal, of variable expression. Type 2N (Normandy) is a rare form of von Willebrand disease due to a qualitative abnormality of vWF that disrupts its ability to bind to factor VIII. The disease biologically combines APTT prolongation, a lower level of factor VIII, and a normal or subnormal rate of vWF, which may suggest a mild form of hemophilia A. This confusion can lead not only to a misdiagnosis but also to inappropriate treatment.

[Galactosemia associated with Rogers syndrome in a 10-month-old infant]. / Galactosémie congénitale associée à un syndrome de Rogers chez une petite fille de 10 mois.

Galactosemia and congenital Rogers syndrome or thiamine-responsive megaloblastic anemia are 2 rare inherited metabolic diseases. The combination of the 2 diseases has never been reported in the literature. We describe the case of an infant followed for congenital galactosemia since the age of 8 days, with thiamine-responsive megaloblastic anemia diagnosed at the age of 10 months. Galactosemia's symptoms occur in the first 2 weeks of life with severe liver disease. Total eviction of the galactose allows complete regression and prevention of early symptoms but does not prevent late complications. Rogers syndrome associates megaloblastic anemia, deafness, and diabetes mellitus that begin in childhood. Supplementation with thiamine allows regression of anemia and prevents the onset of diabetes at least until adolescence.

[Activated partial thromboplastin time prolongation in paediatrics. Retrospective monocentric study at the Nice University Hospital]. / Allongement isolé du temps de céphaline activé en pédiatrie. Étude rétrospective monocentrique au CHU de Nice.

UNLABELLED: The study of hemostasis often arises in paediatrics. Evidence of activated partial thromboplastin time (aPTT) prolongation sometime due to the presence of a circulating anticoagulant (antiphospholipid syndrome [APS]) may be embarrassing for the physician. AIM OF THE STUDY: To evaluate the prevalence of this situation, to identify the leading indicators and assess their impact. PATIENTS AND METHOD: All children aged 1 to 18 years old undergoing blood sample whatever was the reason, at the Nice University Hospital with existing isolated aPTT prolongation, were included. The assessment was completed by a mixing test, calculation of Rosner's index as well as the study of an APS and the measurement of factor VIII, IX, XI, XII. RESULTS: Between July 2006 and March 2008, 27 of 1845 children observed (1.5%) were selected for further study. Mean age was 6.17 years old. For 16 of the patients, aPTT prolongation was fortuitously discovered. Symptomatic subjects were older (9.8 vs. 5.2 years of age; P = 0.03). A significantly higher aPTT was indicative of an APS and predicted a positive Rosner Test outcome. A prolongated kaolin clotting time, observed among the younger subjects (3.45 vs. 8.88 years of age; P = 0.0011), was associated with a high aPTT prolongation (57.3 vs. 42.6s; P = 0.0009). CONCLUSION: In our study, the discovery of a prolongated aPTT is most often incidental and tends to occur during winter. The presence of a highly prolongated aPTT, abnormal kaolin clotting time and positive Rosner Test are strong predictors of the existence of an APS, especially in very young children. These antibodies are nonpathogenic and transitional.

[Neonatal screening for sickle cell disease at the Nice University Hospital: the last 8 years]. / Dépistage néonatal de la drépanocytose au CHU de Nice : bilan des 8 dernières années.

INTRODUCTION: 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 ß-thalassemia) in a target population. Our objective was to evaluate its effectiveness at the Nice University Hospital. POPULATION AND METHODS: 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. RESULTS: 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 ß-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. DISCUSSION: 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. CONCLUSION: Screening for sickle cell disease appears effective in Nice. It seems necessary to continue focusing on the importance of screening among maternity healthcare actors.

[Recombinant activated factor VII in paediatric practice. Universal hemostatic agent?]. / Le facteur VII recombinant activé en pédiatrie. Hémostatique universel?

NovoSeven (eptacog alfa [activated]) is a concentrate of recombinant activated factor VII currently indicated in 3 types of situation: (1) hemorrhagic syndromes in patients with acquired haemophilia or constitutional A or B haemophilia with inhibitor; (2) Glanzmann thrombasthenia in patients with ineffective platelet transfusion due to alloimmunization; (3) constitutional factor VII deficiency. NovoSeven is also used, off label, in a very large number of bleeding conditions or bleeding risk especially in adult's trauma; abdominal, cardiac or chest surgery; gastroenterology; gynaecology and obstetrics or haematology. In these situations and sometimes in the context of randomized trials, against placebo studies, a large number of publications are reported, with variable scientific value according to evidence-based proofs. Studies conducted in children are far fewer and most of them did not achieve a high-level of evidence. However, we wanted to write a synthesis of the paediatric experience reported in the literature. Whereas it is important to build on work done in adults published data, the conclusions drawn from them are not perfectly applicable in paediatric practice. This bibliographical work is not an accurate guide of recommendations but should allow everyone to get an idea of situations where the use of this drug should or might be considered.

[Neonatal Pearson syndrome. two case studies]. / Le syndrome de Pearson : à propos de 2 observations à révélation néonatale.

Among the etiologies of anemia in the newborn, those related to mitochondrial cytopathies are rare. Pearson syndrome is mostly diagnosed during infancy and characterized by refractory sideroblastic anemia with vacuolization of marrow progenitor cells and exocrine pancreatic dysfunction. We describe two diagnosed cases of Pearson syndrome in the early neonatal period caused by severe macrocytic aregenerative anemia. Bone marrow aspiration revealed sideroblastic anemia and vacuolization of erythroblastic precursors. The diagnosis was confirmed by genetic analysis revealing a deletion in the mitochondrial DNA. These two newborns received monthly transfusions. Five other newborns suffering from Pearson syndrome with various clinical symptoms were found in literature. Pearson syndrome, rarely diagnosed in newborns, should be suspected in the presence of macrocytic aregenerative anemia and requires a bone marrow aspirate followed by a genetic analysis from a blood sample.

Bridging the gap between adult and paediatric outcomes in HIV-1 vertically infected children: a single-centre comparison with adult data.

UNLABELLED: Prognosis of HIV-1 infection dramatically improved during the last decade. Meanwhile, treatment-induced virological success has always been different in adult and children patients. AIM: To compare 10 years of follow up in HIV-1 vertically infected children and adult patients. METHODS: Monocentric retrospective longitudinal analysis of vertically HIV-1-infected children and adult patients followed in the Nice University Hospital between 1999 and 2008. Immunological, virological and antiretroviral treatment data were recorded. RESULTS: Forty children and 1752 adult patients were included. Between 1996 and 2008, the percentage of children receiving HAART increased from 3.2% to 91%. Mean CD4% in the paediatric group remained stable between 29 +/- 8.1% in 1998 and 30 +/- 9.4% in 2008. Mean adult CD4-cell count significantly increased from 410 in 1998 to 556 cells/mL in 2008. Logistic regression analysis showed that the children-to-adult difference for indetectability (HIV PCR-RNA below 400 copies/mL) was significant (p < 0.0001) with an odds ratio of 0.61 (CI(95th): 0.52-0.72). Year-to-patient interaction was also significant with a decreasing divergence over time (p: 0.038). CONCLUSION: Nowadays as in adult patients, the control of HIV-1 replication is achieved in nearly eight of 10 children and the percentage of patients with severe immunodeficiency dramatically decreased compared with the mid 1990s.

[High-dose intravenous immunoglobulin therapy and neonatal jaundice due to red blood cell alloimmunization]. / Immunoglobulines polyvalentes intraveineuses et ictère néonatal par allo-immunisation érythrocytaire.

Neonatal jaundice resulting from immunological hemolysis is not uncommon. While it is possible to prevent a large number of Rh-isoimmune hemolytic diseases by administration of specific anti-D immunoglobulins to the mother, the prevention of incompatibility in the ABO groups is not feasible. In spite of advances made in the use of phototherapy, and in order to avoid kernicterus, the treatment of these jaundices can require one or several exchange transfusions (ET), a therapy which is not devoid of risk. For some time now, the data concerning the efficiency of high-dose intravenous immunoglobulin therapy (HDIIT) in the treatment of these jaundices have been increasing. A review of the literature shows that, if used as soon as possible in newborn infants over 32 weeks of gestation age, afflicted with Rh or ABO hemolytic disease, the HDIIT brings about, with no undesirable side effects, a significant decrease in the ET number as well as a significant reduction in the length of phototherapy and hospitalization. The data suggesting that HDIIT could increase the risk of late transfusion is open to controversy.

[A case of acquired encephalopathy in a child. A cause that we thought had disappeared]. / Un cas d'encéphalopathie acquise de l'enfant. A propos d'une cause que l'on croyait disparue.

Subacute central nervous system infection must be considered in any infant presenting with progressive encephalopathy. We present the case of an 18-month-old child with normal neuromotor development until the age of 14 months admitted for spastic hypertonia of the legs and arms associated with axial hypotonia. The mother reported that she recently had been found to be HIV-seropositive. HIV antibodies were negative during the first trimester of pregnancy. On the child's blood sample, the HIV test was positive associated with a major decrease in CD4 cell count. Viral load (ARN-PCR) was 720 copies par millilitre. On brain MRI, hypersignals were found in the white matter. HIV related encephalopathy caused by maternal fetal transmission was diagnosed. After 2 months of antiretroviral treatment (azidothymidine, lamivudine, and boosted lopinavir), the child's neurological condition improved. HIV infection must be suspected in all infants with progressive encephalopathy. The HIV test in pregnant women must be proposed at the beginning of pregnancy and repeated during the last trimester.

[6-mercaptopurine-related hand-foot syndrome in a four-year-old child]. / Syndrome mains-pieds secondaire à la prise de 6-mercaptopurine chez un enfant de quatre ans.

BACKGROUND: Hand-foot syndrome (HFS) is a dose-dependent cutaneous side effect of cytostatic chemotherapy. It has also been described under the names of acral erythema and palmoplantar erythrodysesthesia. We report a case of HFS during treatment of acute lymphoblastic leukemia with 6-mercaptopurine (6-MP) (Purinethol) in a four-year-old child. PATIENTS AND METHODS: A four-year-old boy treated for acute lymphoblastic leukemia developed dry and painful palmar and plantar erythema with fissures. The rash began three weeks after up-titration of 6-MP. There was no past history of cutaneous disease and no other potential trigger factors. The rash ceased after 6-MP withdrawal. DISCUSSION: To our knowledge, this is the first case of HFS due to 6-MP therapy in a child. 6-MP is a major reference drug for the management of acute lymphoblastic leukemia. Numerous cytostatic drugs have been involved in such eruptions.

[Management of autoimmune thrombocytopenic purpura: a prospective study of 147 children from the regional network RHémaP]. / Purpura thrombocytopénique auto-immun: à propos d'une cohorte prospective de 147 enfants pris en charge dans le réseau d'hématologie pédiatrique des régions PACA et Corse (RHémaP).

AIM: Assessment of the impact of guidelines from a regional pediatric network to standardize the management of childhood immune thrombocytopenic purpura (ITP). MATERIALS AND METHODS: Consensus guidelines were drawn up in centers of the pediatric network for hematological diseases, RHémaP, and a cohort of children referred for ITP in these centers was set up. A 1-year follow-up was recorded for each patient over a 43-month period. RESULTS: We report data from a cohort of 147 children. At diagnosis, we recorded severe thrombocytopenia (median=8G/l) and 141 children had hemorrhagic symptoms (96%). Only 23 children had a bone marrow aspiration (BMA) at diagnosis (16.3%), which meant a high level of implementation of the RHémaP recommendations (96%) since indications of BMA were limited to rare indications. For 135 children (91.8%), treatment fulfilled the RHémaP guidelines that were mainly based on the platelet count: 121 received intraveinous immunoglobulin (IVIG) and 14 were not treated. Among those who received IVIG, 110 were good responders (91%) at the 96-h evaluation (platelet count greater than 20G/l), nine (7.4%) were poor responders, and 1 died of intracranial hemorrhage. At 6 months, chronic ITP was observed in 40 children (32.8%). Chronic ITP was associated with a higher platelet count at diagnosis and an older age (p<10(-3) and p=10(-3), respectively). CONCLUSION: The practices recorded over a 43-month period in our cohort fulfilled the RhémaP guidelines and we conclude that we managed to standardize regional practices for children with ITP. We observed conventional epidemiological characteristics in this cohort. Older children and higher platelet count at diagnosis were significantly associated with higher frequency of chronic ITP.

[Second pregnancies in HIV-1-infected women. A prospective monocentric study]. / Secondes grossesses chez les femmes VIH-1 séropositives. Etude prospective monocentrique.

OBJECTIVES: To evaluate the influence of successive pregnancies on the materno-foetal prognosis in a population of HIV-infected women. Clinical, biological data and treatment strategies were compared during iterative pregnancies. PATIENTS AND METHODS: We conducted a monocentric prospective study between August 1995 and January 2007 in a French university hospital (Nice). RESULTS: Twenty-six HIV-infected women had two consecutive pregnancies during our study. We noticed an increase in CD4 cell count between the two pregnancies. Viral load variations were non significant. The maternal's prophylaxis changed. Percentage of HAART increased from 26 to 54%. Modes of delivery, HIV or treatments side-effects remained the same between the successive pregnancies. DISCUSSION AND CONCLUSION: Successive pregnancies do not seem to influence the materno-foetal prognosis related to HIV infection.

[Polycythemia vera and JAK-2 mutation in childhood: a case report]. / Polyglobulie de Vaquez et mutation JAK-2 chez l'enfant: à propos d'une observation.

Erythrocytosis is a rare disorder in childhood and is mainly secondary to causes such as long-term chronic cardiopulmonary diseases or haemoglobin dysfunction. In some cases, polycythaemia is found when renal, hepatic or cerebellar tumours are diagnosed. Polycythemia vera (PV) is uncommon in paediatrics and usually clinical and biological features are used to diagnose and classify PV. The V617F mutation of JAK-2 has been described recently and is found in almost 90% of adult patients with PV. This mutation allows now a reliable and early diagnosis. Therapeutic management is based on phlebotomy and cytoreductive therapy. In young adults and children, interferon alpha is theoretically superior as it is effective and there is no risk of inducing leukemia. We report here a case of PV in a 10-year-old girl with the V617F JAK-2 mutation.

Successful use of recombinant factor VIIa for management of severe menorrhagia in an adolescent with an acquired inhibitor of human thrombin.

UNLABELLED: Antibodies directed against human thrombin are exceedingly rare, having only been reported in adult patients with underlying diseases. Consensus on the most appropriate management has not yet been reached. A 12-y-old girl presented with intractable menorrhagia several days after an acute infectious episode. Laboratory tests revealed disturbed clotting tests: prothrombin index 17%, activated partial thromboplastin time >150 s, thrombin time >120 s, and failure to achieve correction with a normal pooled plasma. Further studies demonstrated the presence of an antibody directed against human thrombin. Viral serology revealed a 1/128 titre for adenovirus. Massive haemorrhage was unresponsive to standard treatments, but intravenous administration of recombinant factor VIIa resulted in a successful outcome. CONCLUSION: This is the first report of an anti-human thrombin antibody associated with severe bleeding in a child. Recombinant factor VIIa could represent a novel therapeutic approach for such patients.

[HIV exposure accidents in children. Experience at the emergency admission services of the CHU of Nice]. / Accidents d'exposition au VIH chez l'enfant. Expérience du service d'admission d'urgence du CHU de Nice.

UNLABELLED: Accidental exposure to human immunodeficiency virus (HIV), either by injury with a discarded syringe or after sexual abuse, increases among the children population. PATIENTS AND METHODS: The entire period of the study was seven-year. Twenty-eight children (14 males, 14 females) underwent three visits after an accidental exposure at Day 0, Day 30th and Day 90th. During each visit, a physical examination, liver enzymes, Ag P24, PCR-RNA HIV, B, C hepatitis serologies were performed. An antiretroviral prophylaxis was proposed when a high risk of HIV transmission was recognized. Anti hepatitis B globulins were administrated when no previous immunization had been made. RESULTS: The median age was 9.3 years (range: 1.5 to 16.7 years). 93% of the children consulted within 48 hours after exposure. Five of them consulted after a sexual aggression with penetration, two after a mucosus exposition and two after deep needle injuries. The source of the contamination was known in five cases. Nine patients were given an antiretroviral treatment for four weeks (seven bitherapy, two tritherapy), with no major side effects. Eighteen and 11 children were seen at the second and third visits, respectively. No case of HIV or HCV infection was observed. CONCLUSION: No case of infection after injury with a discarded syringe was found in our study. This situation differs from what is observed in health care workers, where the higher risk factor is observed. Even if no contamination was found after sexual aggression in our population, the risk of HIV is actual. This is why we propose an antiretroviral prophylaxis against HIV in only one indication, corresponding to sexual penetration.