Statistical analysis of mitochondrial pathologies in childhood: identification of deficiencies using principal component analysis.

Mitochondrial pathologies are a heterogeneous group of metabolic disorders that are frequently characterized by anomalies of oxidative phosphorylation, especially in the respiratory chain. The identification of these anomalies may involve many investigations, and biochemistry is a main tool. However, considering the whole set of biochemical data, the interpretation of the results by the traditionally used statistical methods remains complex and does not always lead to an unequivocal conclusion about the presence or absence of a respiratory chain defect. This arises from three main problems: (a) the absence of an a priori-defined control population, because the determination of the control values are derived from the whole set of investigated patients, (b) the small size of the population studied, (c) the large number of variables collected, each of which creates a wide variability. To cope with these problems, the principal component analysis (PCA) has been applied to the biochemical data obtained from 35 muscle biopsies of children suspected of having a mitochondrial disease. This analysis makes it possible for each respiratory chain complex to distinguish between different subsets within the whole population (normal, deficient, and, in between, borderline subgroups of patients) and to detect the most discriminating variables. PCA of the data of all complexes together showed that mitochondrial diseases in this population were mainly caused by multiple deficits in respiratory chain complexes. This analysis allows the definition of a new subgroup of newborns, which have high respiratory chain complex activity values. Our results show that the PCA method, which simultaneously takes into account all of the concerned variables, allows the separation of patients into subgroups, which may help clinicians make their diagnoses.

Mapping of spinocerebellar ataxia 13 to chromosome 19q13.3-q13.4 in a family with autosomal dominant cerebellar ataxia and mental retardation.

We examined a large French family with autosomal dominant cerebellar ataxia (ADCA) that was excluded from all previously identified spinocerebellar ataxia genes and loci. The patients-seven women and a 4-year-old boy-exhibited slowly progressive childhood-onset cerebellar gait ataxia associated with cerebellar dysarthria, moderate mental retardation (IQ 62-76), and mild developmental delays in motor acquisition. Nystagmus and pyramidal signs were also observed in some cases. This unique association of clinical features clearly distinguishes this new entity from other previously described ADCA. Cerebral magnetic-resonance imaging showed moderate cerebellar and pontine atrophy in two patients. We performed a genomewide search and found significant evidence for linkage to chromosome 19q13.3-q13.4, in an approximately 8-cM interval between markers D19S219 and D19S553.

[Detection of respiratory syncytial virus using immunohistochemistry. Report of 53 cases of sudden infant death]. / Mise en évidence du virus respiratoire syncytial par méthode immuno-histochimique. A propos de 53 cas de mort subite du nourrisson.

We analyzed 53 cases of sudden infant death to detect immunohistochemical expression of respiratory syncytial virus on pulmonary sections. The virus was identified in 7 cases. The immunohistochemical staining was intracytoplasmic and mainly observed in bronchioles. Among these 7 cases, 6 showed severe pulmonary lesions which were assumed to be accountable for decrease. The inflammatory lesions related to respiratory syncytial virus were diffuse, located with the same intensity to either bronchi, bronchioles, alveoles and upper respiratory tract. The immunohistochemical staining was markedly heterogeneous, requiring numerous pulmonary samples.

[Allergy to snails and mites in children]. / Allergie à l'escargot et aux acariens chez l'enfant.

BACKGROUND: Anaphylactic reactions after consumption of snails by patients sensitized to house-dust mites have been reported several times. CASE REPORT: Two 8- and 10-year old children sensitized to house-dust mites developed Quincke's oedema after eating snails. Immunoallergologic investigations including pricks-test, labial test, IgE Rast confirmed associated allergy between snails and house dust mites. CONCLUSION: Considering the potential severity of anaphylactic reactions, it is necessary to warn children allergic to house dust mites and their parents about the high risk of associated allergy with snails.

[Clinico-immunological study of 16 cases of benzoate intolerance in children]. / Une étude clinico-immunologique de 16 cas d'intolérance aux benzoates de l'enfant.

The authors report a sery of 16 cases of intolerance to the benzoates in children. Sixteen children (9 boys and 7 girls) were directed to the Hospital of Tarbes from June 1995 to July 1995, for recurring urticaria (7/16) combined with asthma (1/16), atopic eczema (2/16), dermorespiratory syndrome (2/16) and asthma (1/16). All were subject to an immunological examination comprising alimentation inquiry, prick test, IgE determination, RAST, oral provocation test to benzoates, which establishes the diagnosis, whose confirmation is certified by the benefit of the food eviction. To conclusion, the authors underline several points: the presumable underestimation of the intolerance, the often mentioned atopic familial context, the observed pathology (urticaria, asthma, eczema), the importance of the provocation test. Finally, besides food such as grey shrimps, sodas and antibiotic syrups, one finds benzoates in the antiallergic syrups initially prescribed as a preventive measure.

[Asthma and intolerance to benzoates]. / Asthme et intolérance aux benzoates.

BACKGROUND: Some foods and drug additives may induce allergic reactions. CASE REPORT: A girl with a family history of asthma in both parents developed asthma in her early life. She was successfully given continuous bronchodilator therapy until the age of 7 years. At that time, she had more frequent and severe exacerbations (8 within 10 months) despite reinforced continuous treatment. Oral challenges with bisulfite and sodium benzoate, both additives abundantly ingested by the patient, revealed heightened sensitivity to administration of sodium benzoate. Avoidance of this additive was followed by complete and prolonged disappearance of episodes of coughing and wheezing. CONCLUSION: Adverse reactions to benzoate in this patient required avoidance of some drugs, some of those classically prescribed under the form of syrups in asthma.

[Turner's syndrome and isoforms of LH and FSH. Value of polyclonal enzymatic techniques]. / Syndrome de Turner et isoformes de LH et FSH. Intérêt des techniques enzymatiques polyclonales.

BACKGROUND: The glycoproteic hormones, LH and FSH, circulate under heterogenous molecular forms, the isoforms. The more acidic isoforms of FSH are found in hypogonadic patients and a displacement towards the basic forms is observed during substitutive treatment. CASE REPORT: A 13 year-old girl with Turner syndrome was examined for pubertal delay. Ultrasonography failed to see both ovaries and endocrine investigations showed a type P1 response (LH-RH test using immunological method). Control of hormonal levels by a polyclonal immunoenzymatic method confirmed primary hypogonadism. CONCLUSIONS: Radioimmunological methods using monoclonal antibodies can underevaluate FSH and LH levels under circumstances in which the distribution of isoforms may vary. Discrepancy must lead to the measure of gonadotrophins using polyclonal immunoenzymatic methods.

[Mid-term outcome of 2 cases with maple syrup urine disease: role of liver transplantation in the treatment]. / Devenir à moyen terme de deux cas de leucinose: place de la transplantation hépatique dans le traitement.

BACKGROUND: Dietary treatment of maple syrup urine disease remains difficult; chronic nutritional support in the child does not always avoid acute crises so that liver transplantation may represent an alternate choice in some cases. CASE REPORTS: Two gypsy cousins were born by an interval of 4 days; both had maple syrup urine disease and were similarly treated from the first days of life. They were given exchange transfusions followed by diet restricted in the branched chain amino acids, maintaining normal growth and plasma leucine concentrations under 7 mg/100 ml. Laura, at 10 years, was retarded at school. Compliance to school attendance was limited by her diet problems. Helen suffered at 7 yr 3 mo from liver failure due to hepatitis A virus infection which required liver transplantation. Protein intake was normal 1 week later. At 10 years, she presented with the same degree of school retardation as her cousin, and was placed in the same class. CONCLUSION: Liver transplantation may be effective for treating metabolic problems in MSVD without significative difference between outcome post classic treatment or post liver transplantation.

[Acute hepatopathy compatible with Reye's syndrome in 3 children treated by chemotherapy]. / Hépatopathie aiguë compatible avec un syndrome de Reye chez trois enfants traités par chimiothérapie.

BACKGROUND: Chemotherapy for malignant diseases sometimes leads to hepatic toxicity. Reye's syndrome has not been described in such a situation. CASE REPORTS: Three children, 4, 5 and 6 years-old, were treated for lymphoma or acute lymphoblastic leukemia. They were given polychemotherapy including drugs that were not potentially hepatotoxic. During remission, they suddenly developed manifestations such as neurologic disturbances, hepatomegaly, increased activity of liver enzymes, and microvesicular steatosis. These disturbances were consistent with the diagnostic criteria for Reye's syndrome recommended by the Centers for Disease Control. Factors such as viral infection, salicylate administration, primary metabolic disorder were not present. One child died and the other two recovered completely. CONCLUSION: Patients given chemotherapy, even though the relationship between them remains to be determined, may develop manifestations compatible with a diagnosis of Reye's syndrome.

[Association of Moebius syndrome and hypopituitarism due to a midline anomaly. A case report]. / Association d'un syndrome de Moebius et d'un hypopituitarisme par anomalie de la ligne médiane. A propos d'un cas.

A 14 year old patient had both Moebius anomalad with arthrogryposis and growth hormone deficiency due to a midline defect. This combination suggests an abnormality in the organization of the neural crest and homologous neural tube segment.

[Early neurotoxicity of high-dose of methotrexate and tetrahydrobiopterin deficiency]. / Neurotoxicité précoce du méthotrexate à haute dose et déficit en tétrahydrobioptérine.

Transient neurologic dysfunction associated with high-dose methotrexate and citrovorum factor rescue (MTX-CF) has been previously reported. At the biochemical level, there are at least two important pathways in central nervous system metabolism which might be disturbed by MTX: MTX may deplete the cell of the de novo synthesis of purine nucleotides and thymidylate through its action on dihydrofolate reductase (DHFR), and also inhibit dihydropteridine reductase (DHPR), an enzyme maintaining the cofactor of phenylalanine-hydroxylase in its active tetrahydrogenated form (tetrahydrobiopterin), and hence interfere with the supply of the neurotransmitters derived from tyrosine and tryptophan. We describe such a neurologic disease in a patient with acute lymphoblastic leukemia (ALL) receiving chemotherapy. Significant increase in cerebrospinal fluid biopterins supports the hypothesis of an inhibition of dihydropteridine reductase by MTX, and provides additional suggestions in terms of etiology, diagnosis and treatment.

[Cervical spondylodiscitis caused by Kingella kingae. Apropos of a case]. / Spondylodiscite cervicale à Kingella kingae. A propos d'un cas.

We report a new case of spondylodiscitis due to Kingella kingae in a 19-month-old infant who had torticollis as the first manifestation. The main characteristics of Kingella kingae infections are reviewed: frequency of ENT and joint localizations, slow course, difficult clinical and bacteriological diagnosis, and satisfactory susceptibility to antimicrobial agents.

[Delayed severe decompensation of leucinosis. Significance of emergency blood exchange transfusion. Apropos of 2 cases]. / Décompensations sévères tardives des leucinoses. Intérêt de l'exsanguino-transfusion en urgence. A propos de deux cas.

The observations of two gypsy cousins born to consanguineous parents and exhibiting classical leucinemia are reminders that severe, life-threatening ketotic decompensations may occur at any time. Emergency exchange-transfusions in these two children aged 3 and 5 years reversed the course of extremely severe attacks. Medium term evaluations showed very satisfactory neuropsychologic development in both children. Pathogenesis and prevention of such episodes are discussed.

[Iatrogenic Cushing syndrome in infants. Report of a case with dwarfism]. / Syndrome de Cushing iatrogène du nourrisson. Une observation avec nanisme.

We report a case of iatrogenic Cushing syndrome with dwarfism (-6 SD) in an eight-month-old infant. The respective role of exposure to corticosteroids in utero (the mother took 30 mg prednisolone per day throughout pregnancy) and postnatally (oral prednisolone, prednisolone in breast milk, and betamethasone cream) is discussed. Two other features are pointed out, i.e. presence of a food allergy and favorable outcome under hydrocortisone therapy.

[Primary epidermoid carcinoma of the mandible. Apropos of a case]. / Carcinome épidermoïde primitif de la mandibule. A propos d'une observation.

A rare case of primary central squamous-cell carcinoma of the mandible is reported. Etiology, pathogenesis, clinical features and differential diagnosis are discussed.

[Rescue from sudden death syndrome and allergy to milk proteins (apropos of a case)]. / Syndrome de rescapé de mort subite et allergie aux protéines du lait (à propos d'une observation).

Allergy to milk proteins may be responsible for the syndrome of unexplained, sudden death of infants, but well-documented cases are rare. The authors report an observation where clinical history and complementary investigations support the incrimination of this factor.