Novel mutations in exon 6 of the GFAP gene affect a highly conserved if motif in the rod domain 2B and are associated with early onset infantile Alexander disease.

Alexander disease is a rare disorder of cerebral white matter due to a dysfunction of astrocytes. The most common infantile form presents as a megalencephalic leukodystrophy. Mutations of the GFAP gene, encoding Glial Fibrillary Acidic Protein, have been recognized as the cause of Alexander disease. Glial Fibrillary Acidic Protein is the major intermediate filament protein in astrocytes, its functional rod domain is conserved in sequence and structure among other intermediate filament proteins. We report here two cases of infantile Alexander disease with early onset and severe course, caused by DE NOVO mutations A364 V and Y366C. Both affected GFAP residues are part of a highly conserved coiled-coil trigger motif in the C-terminal end of segment 2B, probably required for the stability of intermediate filament molecules. Comparable effects are seen with mutations of the corresponding residues of the gene coding for keratin 14, another intermediate filament, this further supports the hypothesis that these positions of the trigger motif are generally critical for a normal function of intermediate filaments.

[Acute hemolytic anemia caused by glucose-6-phosphate dehydrogenase deficiency]. / Akut haemolytisk anaemi forårsaget af glukose-6-fosfat-dehydrogenasemangel.

Glukose-6-phosphate dehydrogenase (G6PD) is essential in protecting the red cell from oxidative damage. We report a case of acute haemolysis in a child with G6PD deficiency. Because of the severity of the anaemia, the patient was treated with blood transfusions and recovered fully. There are two main variants of G6PD deficiency (the Mediterranean variant and variant A) with different clinical profiles. Acute haemolytic attacks are induced by certain drugs, by infections or, in the Mediterranean variant, by ingestion of fava beans (favism). Increased awareness of this condition is necessary in Denmark because of increased immigration.

[Clinical manifestations caused by group A streptococci]. / Kliniske sykdomsbilder forårsaket av gruppe A-streptokokker.

We describe the symptomatology of different disease entities caused by group A beta-hemolytic streptococci (Streptococcus pyogenes, GAS). The case histories of four patients, two of whom died, emphasize the severity of certain clinical manifestations of GAS-infections. A 34 year-old woman was admitted to hospital four days after start of the symptoms. She presented a clinical picture very similar to that observed in fulminant meningococcal septicaemia; i.e. extensive skin haemorrhages, circulatory collapse, and multiple organ failure. She died within 12 hours of admission. GAS were isolated in blood culture. A seven day-old girl died before admission to hospital. GAS were isolated in blood cultures, cerebrospinal fluid and from her nose and throat. An eight year-old, psychomotoric retarded girl developed a severe left-sided pneumonia, empyema and scarlatina. GAS were detected in throat culture. She responded poorly to high doses of benzylpenicillin given intravenously. She recovered rapidly after thoracotomy and decortication of her left lung. Finally, we describe the case of an 11 year-old boy with rheumatic fever without cardiac involvement. The reported cases underline the need for careful diagnosis and penicillin treatment in cases of GAS-infections.

45,X/47,XY,+13 mosaicism and Crohn's disease.

The unusual karyotype 45,X/47,XY,+13 in an 8.5-year-old girl with the Turner phenotype is described. She displayed none of the phenotypic manifestations of trisomy 13. The patient suffered from Crohn's disease, which is known to be associated with the Turner syndrome. To our knowledge this is the first reported case of Crohn's disease in a patient with 45,X and Y chromosome mosaicism.

Biologically active peptide-containing fractions in schizophrenia and childhood autism.

It is well documented that peptides have a major role in the effective functioning of higher animals at all levels from enzyme stabilization to homeostatic mechanisms governing essential functions such as eating, sexual behavior, and temperature regulation. The effects of exogenously administered peptides on neurotransmitter release, uptake, metabolism and behavioral consequences are also well established. We have attempted to extend these findings by postulating peptidergic neurons as transducers of multisignal inputs, and that development of pathological states may be due to genetically-determined reduced levels of activity of key peptidases, leading to excretion of regulatory peptides into the circulation. We have been able to demonstrate that, in schizophrenia and autism (in well defined clinical cases), the patterns of peptides and associated proteins from urinary samples differ considerably from each other and from normal controls. In addition to this, further purification of the material obtained has led to the discovery of a number of factors capable of modulating the function of major neurotransmitters. Some of these are in the final stages of characterization as peptides, while the remainder are also probably peptides, as purification has been followed by both biological testing and chemical analysis for peptidic material. We have outlined a number of parameters which we consider relevant in any attempt to put psychiatric disorders on a biological foundation. Any new advances in the neurochemical understanding of such disorders must take into consideration the observations of several different disciplines including genetics and psychology. However, at this stage of research it is far too early to speculate on the relevance of the various biological activities to the etiology and symptomatology of schizophrenia and childhood autism.

Relapse of Hemophilus influenzae type b meningitis after combined antibiotic therapy: report of a case.

Antibiotic therapy of bacterial meningitis is being reevaluated due to reports of ampicillin-resistant strains of Hemophilus influenzae type b. The infant reported had a relapse of H. influenzae type b meningitis after an excellent clinical and bacteriologic response to an initial course of combined antibiotic therapy including chloramphenicol. This relapse is postulated to be due to localized cerebral vasculitis which was not treated for a sufficient period of time during the initial course of therapy. The patient responded well to a second course of penicillin and chloramphenicol. Since the use of pencillin and chloramphenicol will be increasing, the clinician should be aware that bacteriologic relapse of H. influenzae type b meningitis may occur with chloramphenicol therapy.