X linked spastic paraplegia (SPG2): clinical heterogeneity at a single gene locus.

X linked hereditary spastic paraplegia is a rare condition that has been divided into two forms (the pure spastic form and the complicated form) as a function of clinical course and severity. A gene for pure hereditary spastic paraplegia (SPG2) has been mapped to the proximal long arm of the X chromosome (Xq21) by linkage to the DXS17 locus, while a gene for a complicated form of the disease has been mapped to the distal long arm by linkage to the DXS52 locus (Xq28). Here we report on the mapping of a gene for complicated hereditary spastic paraplegia to the Xq21 region by linkage to the probe S9 at the DXS17 locus (Z = 5 at theta = 0.04) in a three generation pedigree. Multipoint linkage analysis supports the distal location of the disease gene with respect to the DXYS1-DXS17 block (cen-DXYS1-DXS3-DXS17-SPG2-tel). The observation of a complicated form of spastic paraplegia mapping to Xq21 raises the difficult issue of variable phenotypic expression, allelic heterogeneity, or even close proximity of two genes for hereditary spastic paraplegia in this region. However, since our study provides clinical evidence for intrafamilial heterogeneity in complicated X linked spastic paraplegia, the present data support the hypothesis of variable clinical expression of a single gene at the SPG2 locus, as previously suggested for SPG1. Finally, we report here what we believe to be the first evidence of clinical expression in heterozygous carriers, a feature that is relevant to genetic counselling in at risk females.

Congenital hypomagnesemia: alternatives to tissue biopsies for monitoring body magnesium status.

We have been monitoring a 12-year-old boy (his present age) suffering from selective magnesium (Mg) malabsorption. After ascertaining his Mg status, we attempted to maintain Mg balance through the use of oral supplements. Plasma and erythrocyte Mg concentrations were monitored at bimonthly intervals. However these measurements did not accurately reflect Mg status and we subsequently measured Mg in the following tissues: lymphocyte, tooth, and hair. Levels of Mg in stable tissues such as temporary teeth and lymphocytes, unfailingly revealed a marked deficit in Mg that was only two-thirds of the normal levels found in the control group. The use of these readily-accessible stable tissues can thus obviate the need for muscle or bone biopsy. Unfortunately the level in hair is higher than in healthy subjects, and thus does not constitute an adequate measure of Mg status.

Monosomy 6q: report on four new cases.

We report on four patients with partial monosomy of the long arm of chromosome 6: two children presenting with an interstitial deletion del(6)(q14q16), the two others presenting with a terminal deletion del(6)(q25qter). These patients are compared with previous reports in the literature: 16 cases of terminal deletion and 17 cases of interstitial deletion. The deletions most often occur de novo. Mental retardation is always described. Dysmorphic facial features range between minor and major. There may be associated visceral abnormalities. After comparing the size and the localisation of the deletions with clinical data, we are now able to suggest a clinical localisation on chromosome 6.

Magnesium and thermoregulation. I. Newborn and infant. Is sudden infant death syndrome a magnesium-dependent disease of the transition from chemical to physical thermoregulation?

The sudden infant death syndrome (SIDS) remains a leading cause of death during the first year. The common epidemiological and pathological data which characterize SIDS include the curve for age at death (with 3 months as modal age), the stigmata of early maternal intrauterine injury, the seasonal predominance in winter, and the absence of an adequate cause of death at autopsy. Some data characterize risk factor subgroups: for example low socioeconomic level, environmental pollution, stress, and mistakes in baby care. Symptoms before death may be lacking, they may be common and non-specific, or rarely they may be acute, corresponding to "apparent life-threatening events" (ALTE). SIDS may be a magnesium-dependent disease of the transition from chemical to physical thermoregulation. This theory originates from a synthesis of our present knowledge of SIDS, maternal magnesium status, and thermoregulation in the baby. It is consistent with all the epidemiological and pathological prerequisites characterizing SIDS. It eliminates the hiatus between relatively minor thermal stress and induced lethal thermal stroke. Logical scepticism about the role of an implausible lethal superacute magnesium deficiency is no longer justified with regard to well established chronic marginal magnesium deficiency. Further experimental and clinical research will be interesting, i.e. ex vivo studies on brown adipose tissue (BAT) and magnesium deficiency under various conditions of thermal exposure. But even now the theory leads to three therapeutic consequences: (1) the need to define the importance of magnesium deficiency in diagnosis and treatment of ALTE; (2) an assessment of the use of new techniques of rewarming (i.e. extracorporeal circulation) in hypothermia cases to distinguish cot death from "apparent death"; (3) investigation of the prevention of SIDS with magnesium through a blinded and randomized multicentre prospective cooperative study of magnesium supplementation in pregnant and lactating women, followed not only in the mother, fetus, and neonate at birth, but also through the first year of life.

[Necrotizing enterocolitis in a premature infant]. / Entérite aiguë nécrosante du prématuré: rôle possible d'un adénovirus.

We report a case of necrotizing enterocolitis in a 30 weeks old premature infant fed with breast milk. No ischemic etiology was present. Bacteriological and parasitological investigations were found to be negative. Only, a positive latex agglutination test for Adenoviruses was detected in stools collected the day of the bloody diarrhea. Detailed microbiological examinations are emphasized by this unusual finding because the role of pathogens in this disease deserves further understanding.

Severe selective magnesium malabsorption: tests of tolerance of oral magnesium supplements.

Since his birth, we have been monitoring a 12-year-old boy suffering from selective severe magnesium malabsorption. Our essential problem is to prepare a form of galena with acceptable taste, tolerated by the digestive tract and well absorbed; also, the carrier compound must not cause short- or long-term side effects. An additional factor is the steadily increasing need for magnesium from 1 mmol/kg.d at 1 year to 14 mmol/kg.d at present age (345 mg/kg.d). The galena forms currently on sale were, with the exception of lactate and pyrollidone carboxylate, immediately rejected since they contain insufficient Mg2+. Following short trials resulting in diarrhoea, the other two preparations were also rejected. We then constituted - and also abandoned - our own galena compounds: aspartate (bitterness), aspartate + glycerophosphate (GLP) (bitterness), glutamate + GLP ('Chinese restaurant syndrome' and fear of the long term toxic effect of the glutamate), gluconate (excessive volume: 11/1 proportion with Mg2+). A recent test featuring GLP of Mg 40 g + cocoa butter 40 g + cocoa 10 g, brought about vomiting and diarrhoea, and was not adequately absorbed. The best tolerated formula is: Mg GLP 21.33 g; saccharose 6 g; aspartam 1 g; gelatin 0.5 g; citric acid, conserving agent, fruity aroma; water: qs 100 g. Such composition yields a caramel cream absorbed in five small portions, at a daily quantity of 375 g (80 g GLP Mg, 10 g Mg2+). Vitamin B6, which promotes intestinal absorption of magnesium, must be given separately in tablet form at a dose of 1 g/d, since it causes nausea if it is included in the Mg preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

[Neonatal exchange transfusion with irradiated whole blood. Preliminary results]. / L'exsanguino-transfusion néonatale avec sang total irradié. Résultats préliminaires.

Some clinical manifestations following exchange transfusion (ET) could result from graft versus host disease secondary to the introduction of viable foreign T lymphocytes: skin rash, fever, acute and sometimes bloody diarrhea or enterocolitis. Between February 1985 and January 1989 the blood used for 31 ET was irradiated at 40 grays. We compared the manifestations occurring during the days following ET to those occurring after 44 previous ET with non irradiated blood during the period January 1981 to January 1985. From 1981 to 1985, 13 of 44 infants developed problems within 3 days following ET: an erythematous macular skin rash in 4; gastrointestinal manifestations (diarrhea, vomiting and rectal bleeding, necrotizing enterocolitis) in 7; both skin lesions and a gastrointestinal problem in 2. Since 1985, 27 infants had no problems whereas only 4 developed gastrointestinal or cutaneous manifestations: NEC in a preterm infant, abdominal distension with rectal bleeding, fever and petechial rash in 2 infected infants. These data show a dramatic decrease of complications since the irradiation of blood products has been started: 30% with non irradiated, 13% with irradiated blood.

Multibranched chromosomes in the ICF syndrome: immunodeficiency, centromeric instability, and facial anomalies.

A new patient with the rare ICF syndrome (immunodeficiency, centromeric heterochromatin instability, and facial anomalies) is reported. The six patients previously reported in the literature are reviewed. The main clinical and cytogenetic characteristics of the syndrome are discussed.

[Congenital pseudohypoaldosteronism: apropos of 6 cases]. / Le pseudohypoaldostéronisme congénital: à propos de 6 observations.

Pseudohypoaldosteronism is a congenital disorder, with an as yet unclear pathophysiology, mode of inheritance and frequency. We have recently diagnosed 6 cases in a relatively short period of time, which suggests that the frequency of the disease may be underestimated. This may be due to a high variability in the clinical expression and to the existence of asymptomatic forms. Autosomal dominant and autosomal recessive modes of inheritance have been reported which probably correspond to different underlying mechanisms.

[Hydrocephalus and the Goldenhar syndrome]. / Hydrocéphalie et syndrome de Goldenhar.

Two female babies with Goldenhar syndrome have, the first an aqueductal stenosis, the second repetitive spells of pain and strain of the anterior fontanel. Aqueductal stenosis, hydrocephalus or intracranial hypertension are not previously described in this syndrome.

[Nasal cannula, a simple, not very cumbersome, and efficacious means to induce a positive expiratory pressure in neonatology]. / La canule nasale, moyen simple, peu onéreux et efficace pour provoquer une pression expiratoire positive en néonatologie.

The authors report their 6 years experience in the use of a CPAP nasal cannula in 91 children. Their indications are idiopathic respiratory distress (hyaline membrane disease) stage I, II, III in children more than 1500 g, stage I and II for those less than 1500 g; transitory respiratory distress; cesarean lung; amniotic inhalation after aspiration and physiotherapy. In 75 newborns this method rendered tracheal intubation unnecessary. There were few side effects and very few serious accidents. The authors propose this method to be a substitute to tracheal intubation and mechanical ventilation, for the units of neonatal intensive care, or nurseries, specially in tropical countries, without important medical supplies. They give modalities, indications and applications of this innocuousness, easy and non-expensive method.