Recessive hereditary methaemoglobinaemia, type II: delineation of the clinical spectrum.

Type II recessive hereditary methaemoglobinaemia (RHM) is a rare disease due to generalized NADH-cytochrome b5 reductase (cytb5r) deficiency. It results in mild cyanosis and severe neurological impairment. The clinical features and long-term outcome are poorly documented, and there are no systematic reviews. We examined six cases of type II RHM, four of which were new, together with 45 previously published cases, in order to establish the range of phenotypic expression. The clinical picture was very similar in most cases, with severe encephalopathy, microcephaly, generalized dystonia, movement disorders and mild cyanosis. The neurological prognosis was poor; in particular, none of the patients walked or spoke. In addition, the possibility of an atypical and milder phenotype was considered. We concluded that children with unexplained severe encephalopathy associated with generalized dystonia should be examined for cyanosis and have a methaemoglobinaemia assay performed. The diagnosis can be confirmed by very low cytb5r activity in both red and white blood cells. Here we report three novel mutations in the NADH-cytochrome b5 reductase gene. Prenatal diagnosis of this extremely severe disease should be proposed to affected families.

A 140 mA cw deuteron electron cyclotron resonance source for the IFMIF-EVEDA project.

In the framework of the IFMIF-EVEDA phase (International Fusion Materials Irradiation Facility-Engineering Validation and Engineering Design Activities), the CEA-Saclay is in charged of the design and realization of the 140 mA cw deuteron source. The IFMIF EVEDA demonstrator will be installed in Japan in the next six years and will have to accelerate the deuteron beam up to 9 MeV. CEA will build the source and the low energy beam line (LEBT) and will test the cw high intensity deuteron production at Saclay. The SILHI source is an electron cyclotron resonance (ECR) source, operating at 2.45 GHz. In 2001, it produced more than 130 mA of deuteron beam in pulsed mode to minimize neutron production. Such a result pushes to develop a new ECR source based on the SILHI design and equipped with a specific extraction system. Several options of the accelerator column will be implemented in order to improve the reliability and the efficiency of the source. The IFMIF source and LEBT design will be reported.

First set of gated x-ray imaging diagnostics for the Laser Megajoule facility.

The Laser Megajoule (LMJ) facility located at CEA/CESTA started to operate in the early 2014 with two quadruplets (20 kJ at 351 nm) focused on target for the first experimental campaign. We present here the first set of gated x-ray imaging (GXI) diagnostics implemented on LMJ since mid-2014. This set consists of two imaging diagnostics with spatial, temporal, and broadband spectral resolution. These diagnostics will give basic measurements, during the entire life of the facility, such as position, structure, and balance of beams, but they will also be used to characterize gas filled target implosion symmetry and timing, to study x-ray radiography and hydrodynamic instabilities. The design requires a vulnerability approach, because components will operate in a harsh environment induced by neutron fluxes, gamma rays, debris, and shrapnel. Grazing incidence x-ray microscopes are fielded as far as possible away from the target to minimize potential damage and signal noise due to these sources. These imaging diagnostics incorporate microscopes with large source-to-optic distance and large size gated microchannel plate detectors. Microscopes include optics with grazing incidence mirrors, pinholes, and refractive lenses. Spatial, temporal, and spectral performances have been measured on x-ray tubes and UV lasers at CEA-DIF and at Physikalisch-Technische Bundesanstalt BESSY II synchrotron prior to be set on LMJ. GXI-1 and GXI-2 designs, metrology, and first experiments on LMJ are presented here.

Differential levels of synovial fluid aggrecan aggregate components in experimental osteoarthritis and joint disuse.

The levels of proteoglycan aggregate components (link protein, keratan sulfate epitope, and total sulfated glycosaminoglycan) were determined in the synovial fluid lavages of dogs with experimental osteoarthritis or disuse atrophy. A model of experimental osteoarthritis was created by transection of the anterior cruciate ligament of the right knee; studies were carried out 6 and 12 weeks after surgery. Joint disuse was studied at 4 and 8 weeks after initiation of the disuse. Recovery after disuse also was studied in joints that had 3 weeks of remobilization after 4 or 8 weeks of disuse. Synovial fluid lavages from the right knee joints of untreated animals were used as controls. The concentrations of keratan sulfate epitope, sulfated glycosaminoglycan, and link protein in the synovial fluid lavages at 6 and 12 weeks after transection of the anterior cruciate were elevated compared with the control values. Similar analysis of the fluid after disuse showed that the levels of keratan sulfate epitope and sulfated glycosaminoglycan were increased compared with the control levels and the levels after transection. However, the concentration of link protein in the fluid after disuse was not significantly different from the control level. The levels of keratan sulfate epitope and sulfated glycosaminoglycan in the synovial fluid lavages after disuse with recovery were high, but the levels of link protein remained low. The results indicate that the catabolism of proteoglycan aggregates in articular cartilage during early osteoarthritis and disuse is different. The determination of keratan sulfate epitope in synovial fluid lavages appears to provide a relatively general indication of proteoglycan catabolism, whereas increased levels of link protein may be more indicative of cartilage degeneration.

[Prion diseases and blood transfusion]. / Maladies à Prion et transfusion sanguine.

Prion diseases are lethal disorders, some of which are transmissible by infectious route. Experimental data concerning neuroinvasion indicate that there is a viremia during the migration of the prion agent to the central nervous system. The possibility of accidental transmission via blood products and therefore potential transfusion risk thus arises. The analysis of experimental and epidemiological data available at present contributes to the following conclusion: the potential and theoretical risk for contamination from blood products is not null but mathematically very low, there is no indisputable experimental proof for that risk via systemic route and no case is definite and the risk is probably linked to leukocytes, and especially B lymphocytes. These conclusions are reassuring but nevertheless justify strict epidemiological survey and a reasonable discussion for each transfusion. Some groups of people have to be excluded from blood donors.

[Creutzfeldt-Jakob disease in 4 children treated with growth hormone]. / Maladie de Creutzfeldt-Jakob chez quatre enfants traités par hormone de croissance.

Creutzfeldt-Jakob disease was diagnosed in four growth hormone recipients at the age of 10, 11, 18 and 19 years. To our knowledge, the two first cases are the first instances of Creutzfeldt-Jakob disease recorded in children. Three of them were still being treated with synthetic hormone at the onset of the disease. Neurological disorders: ataxia and diplopia, appeared first, dementia and myoclonus appeared later. Eighteen cases of Creutzfeldt-Jakob disease in growth hormone recipients are now recorded, and the present risk of Creutzfeldt-Jakob disease in pituitary growth recipients is estimated to be 1/300. Because of the long incubation period, new cases are to be feared. Other causes of iatrogenic Creutzfeldt-Jakob disease are reviewed. These facts incite to consider carefully using products of human origin in human therapy. The interactions between growth hormone, prion and host's genomic make-up are still not clear.

[Hereditary methemoglobinemias]. / Les méthémoglobinémies héréditaires.

The different forms of hereditary methemoglobinemia are described. Dominant hereditary methemoglobinemia (hemoglobin M diseases) is due to punctual mutations on the alpha or beta globin chain leading to its permanent oxidation. Recessive hereditary methemoglobinemia is due to a deficit of the NADH-cytochrome b5 reductase, with two different clinical presentations according to whether the deficit is limited to blood cells (type I) or is generalized (type II); the latter is extremely severe and justifies a prenatal diagnosis. Finally, the only known case of recessive hereditary methemoglobinemia due to a deficit of b5 cytochrome is quoted.

[Spasmus nutans: apropos of 16 cases]. / Spasmus nutans: à propos de 16 cas.

UNLABELLED: Spasmus nutans is a syndrome occurring in early childhood. It consists of a triad of symptoms: head nodding, ocular oscillations and anomalous head position. Ophthalmologic and neurological findings are otherwise normal. This syndrome is benign and has spontaneous resolution. PATIENTS AND METHOD: Sixteen patients with spasmus nutans seen from 1980 to 1995 were retrospectively studied. Their present status was evaluated by clinical examination or questionnaire. RESULTS: The age at onset ranged from 1 to 15 months (average 7 months). Thirteen of 16 patients were referred for head nodding, which was a constant manifestation; its direction was horizontal, vertical or rotatory. Nystagmus was present in 14 infants. It was acquired, asymmetrical, bilateral (or unilateral in three cases), rapid, fine, pendular and horizontal. Both head nodding and nystagmus were intermittent. Anomalous head position was present in seven cases, consisting of head tilt or a chin upon/chin down posture. Neuroimaging (13 cases) was always normal. The follow-up in 12 children (up to 2 years) showed a complete resolution of the syndrome in 6 months to 6 years (average 2.5 years). DISCUSSION: The diagnosis was established by the constancy of the characteristic triad and the elimination of the other causes of nystagmus. Isolated head nodding had to be distinguished from bobble head syndrome. In several reported cases, electronystagmography recordings have suggested that head nodding is a compensatory process against nystagmus and that the head tilt allows transient resolution of the nystagmus. CONCLUSION: Spasmus nutans is a self-limiting benign clinical entity. Normal complete ophthalmologic and neurological examination, as well as magnetic resonance imaging (MRI) are necessary to confirm the diagnosis.

[Ovarian insufficiency in congenital galactosemia]. / L'insuffisance ovarienne de la galactosémie congénitale.

Primary ovarian failure was observed in 2 sisters aged 17 and 4 years respectively presenting with congenital galactosaemia. The diagnosis of ovarian failure, clinically suggested in the older girl by the absence of puberty, was confirmed in both cases by a massive increase of baseline and post-stimulation plasma gonadotrophins. The elder sister had extremely low plasma oestradiol levels, and her ovaries were reduced to two strips of fibrous stroma almost devoid of follicles. In both cases the other endocrine glands seemed to be normal. Since the younger girl had received a galactose-free diet from birth, exogenous galactose toxicity could be ruled out. It appears from an analysis of the other 5 published reports that a metabolite of endogenous galactose is responsible for the ovarian lesions. The toxic effects of this metabolite may begin during intra-uterine life or after-birth.

[Dermo-neuro-hypsarrhythmia. Association of a congenital dermatosis and hypsarthymia. 9 cases (author's transl)]. / Dermo-neuro-hypsarythmie. Association d'une dermatose congénitale et d'une hypsarythmie, A propos de 9 cas

These 9 cases confirm that tuberose sclerosis, von Recklinghausen's neurofibromatosis, incontinentia pigmenti, linear warty sebaceous naevus and alopecic naevus resulting in a woolly naevus of the scalp may be complicated by flexion spasms with hypsarhythmia. Early diagnosis of hypsarhythmia makes possible specific treatment with ACTH or hydrocortisone.

[Management of drepanocytic patients]. / Prise en charge des patients drépanocytaires.

Comprehensive supportive care includes outpatient follow up (periodic evaluation of baseline status, psychosocial support, prevention of sepsis through oral prophylactic penicillin in young children and vaccinations, early treatment of acute episodes (painful crises, other vaso-occlusive events, infection, acute anemia...); In adulthood residual organ dysfunction becomes one of the foremost problems. Further, more specific high risk situations (pregnancy, anesthesia) require adequate responses. Early diagnosis, improved strategy of care best achieved in Sickle Cell Centers can reduce mortality and morbidity in the aim of providing a better quality of life.