Mutation analysis a prerequisite for prenatal diagnosis of L-2-hydroxyglutaric aciduria?

The prenatal diagnosis of two subsequent pregnancies of the mother of a patient homozygous for a mutation in the L-2-hydroxyglutarate dehydrogenase gene is described. In the first pregnancy, measurement of L-2-hydroxyglutaric acid in amniotic fluid revealed an affected fetus. This pregnancy was terminated. In the prenatal diagnosis of the second pregnancy, mutational analysis was also included and proved to be of pivotal importance. Despite mildly increased levels of L-2-hydroxyglutaric acid in the amniotic fluid, the fetus was heterozygous for this mutation thus excluding L-2-HGA.

[Congenital hemiplegia. A disease with manifold problems]. / Kongenitale Hemiplegie. Eine Krankheit mit vielen Problemen.

Congenital hemiplegia, defined as unilateral motor disability, is the hemiplegic type of cerebral palsy. The prevalence of congenital hemiplegia is estimated to be about 0.41-0.79/1000 live births. We examined 223 children (122 boys and 101 girls) suffering from congenital hemiplegia at the age of 3 months to 12 years. Mild hemiplegia was found in 31%, a moderate form in 48%, and a severe form in 21%. The upper limb was affected in more than half of the patients, only the lower extremity in one third, and both upper and lower limbs in 20%. Electroencephalographic abnormalities were found in 75.8% of the patients. The most frequent type of epilepsy was complex partial seizures (33%). Severity of the motor handicap, grade of EEG abnormalities, and the prevalence of epilepsy showed a significant correlation. The magnitude of the lesions in neuroimaging directly correlated with these three clinical variables, particularly in children with cortical and subcortical defects (84.2%). Strabismus was the most common visual impairment (17%), while hearing impairment was found in 8% of the patients. Of them, 38.3% showed no cognitive deficits, while those with severe congenital hemiplegia were found to have a lower intelligence quotient.

[Indications for intermittent diazepam prophylaxis in febrile seizures]. / Indikation der intermittierenden Diazepamprophylaxe bei Fieberkrämpfen.

BACKGROUND: In a prospective controlled study we evaluated the efficacy of intermittent diazepam prophylaxis in the recurrence rate of febrile seizures (FS). PATIENTS: A total of 139 children aged between 6 and 36 months, who had a first FS, were enrolled in the study and were randomly allocated to two groups: group (A) that received diazepam prophylaxis and group (B) without prophylaxis. METHODS: All children were followed up for at least 3 years after their first FS. The prophylaxis group (n = 68) received rectal diazepam the first two days of a febrile illness, whenever the temperature was > 38 degrees C (0.33 mg/kg every 8 h on the first day, and 0.33 mg/kg every 12 h on the second day of fever, max. dosage 7.5 mg). The no-prophylaxis group (n = 71) did not receive any prophylaxis at all. Each group was stratified to low, intermediate and high risk subgroups according to the following clinical data: age at the first febrile seizure

[Congenital muscular dystrophy with laminin-a2 deficiency in early infancy: diagnosis and long-term follow-up]. / Kongenitale Muskeldystrophie mit Merosin-(Laminin-a2)-Mangel im frühen Säuglingsalter: Diagnostik und Langzeitverlauf.

Congenital muscular dystrophy (CMD) is a heterogeneous group of neuromuscular disorders characterized by muscle weakness and hypotonia at birth or within the first few months of life. It is inherited in an autosomal recessive pattern. About half of the patients have a deficiency of the alpha-2-chain of laminin (merosin). We describe a case of congenital muscular dystrophy in an infant with laminin-a2-chain deficiency, which appeared hypotonia in early infancy. Diagnosis was made by clinical features and the histological and immunohistochemical studies on muscle biopsy.

Femoral osteomyelitis due to Aspergillus nidulans in a patient with chronic granulomatous disease.

13 cases of osteomyelitis caused by Aspergillus nidulans have been previously reported in patients with chronic granulomatous disease (CGD). All of them have been associated with simultaneous pulmonary infection and have had an extremely poor outcome. We report an unusual case of femoral osteomyelitis due to A. nidulans in a 16-year-old male with CGD, without pulmonary involvement. Treatment with liposomal amphotericin B and granulocyte colony-stimulating factor as well as extensive surgical debridement followed by prolonged treatment with itraconazole resulted in an excellent clinical response.

Interleukin 10 suppresses phagocytic and antihyphal activities of human neutrophils.

We investigated the effects of human interleukin 10 (IL-10) on the antibacterial and antifungal activities of human neutrophils (PMNs) against Staphylococcus aureus and Candida albicans. Incubation of PMNs from healthy volunteers with 20-100 ng/ml of IL-10 at 37 degrees C for 1 h suppressed phagocytosis of serum-opsonized S. aureus (P=0.02) and blastoconidia of C. albicans (P<0.01). In contrast, 2-100 ng/ml of IL-10 had no effect on superoxide anion production upon stimulation with phorbol myristate acetate, N-formylmethionyl leucyl phenylalanine, C. albicans blastoconidia or pseudohyphae; neither did it significantly affect conidiocidal or bactericidal activities of PMNs. However, 20-100 ng/ml of IL-10 significantly decreased PMN-induced damage of C. albicans pseudohyphae (P=0.008). The suppression of phagocytic activity of PMNs against S. aureus and blastoconidia of C. albicans as well as the impairment of PMN-induced hyphal damage may have important implications for understanding the immunosuppressive profile of IL-10 in clinical usage.

Disseminated infection due to Chrysosporium zonatum in a patient with chronic granulomatous disease and review of non-Aspergillus fungal infections in patients with this disease.

We report the first case of Chrysosporium zonatum infection in a 15-year-old male with chronic granulomatous disease who developed a lobar pneumonia and tibia osteomyelitis while on prophylaxis with gamma interferon. The fungus was isolated from sputum and affected bone, and hyphae were observed in the bone by histopathology. Therapy with amphotericin B eradicated the osteomyelitis and pneumonia, but pneumonia recurred in association with pericarditis and pleuritis during therapy with itraconazole. These manifestations subsided, and no recurrences occurred with liposomal amphotericin B therapy. Infections caused by Chrysosporium species are very rare, and C. zonatum has not previously been reported to cause mycosis in humans. This species, the anamorph of the heterothallic ascomycete Uncinocarpus orissi (family Onygenaceae), is distinguished by its thermotolerance, by colonies which darken from yellowish white to buff, and by club-shaped terminal aleurioconidia borne at the ends of short, typically curved stalks. The case isolate produced fertile ascomata in mating tests with representative isolates. The median (range) MICs for our isolate as well as those for two other human isolates and a nonhuman isolate determined by the National Committee for Clinical Laboratory Standards method adapted for moulds were 128 microg/ml (>128 microg/ml) for flucytosine, and 48 microg/ml (32 to >128 microg/ml) for fluconazole.

Incidence of ceftriaxone-associated gallbladder pseudolithiasis.

We prospectively evaluated the incidence of gallbladder pseudolithiasis in children treated with high doses of ceftriaxone for a variety of serious infections. We also monitored the time interval needed for this phenomenon to develop and resolve completely after initiation and cessation of treatment, respectively. Included in this study are 44 children treated with ceftriaxone 100 mg/kg/d divided into 2 equal intravenous doses and followed by serial abdominal sonography. Eleven children developed pseudolithiasis of gallbladder 2-9 d after initiation of ceftriaxone therapy. Six children (54.5%) developed this complication within the first 3 d. Lithiasis completely resolved 8-23 d after the end of treatment. In conclusion, pseudolithiasis of the gallbladder developed in 25% of sick children and completely resolved in all patients. Early development of this complication was not exceptional. It occurred in more than half of these children.

Suppressive effects of interleukin-10 on human mononuclear phagocyte function against Candida albicans and Staphylococcus aureus.

The effects of interleukin (IL)-10, a potent antiinflammatory cytokine, on human monocyte functions against two medically important pathogens, Candida albicans and Staphylococcus aureus, were studied. Incubation with 20-100 ng/mL IL-10 for 2-3 days decreased the fungicidal activity of monocytes against serum-opsonized C. albicans blastoconidia (P

[Experiences with MCT containing fat emulsions in premature and newborn infants]. / Erfahrungen mit MCT-haltigen Fettemulsionen bei Früh- und Neugeborenen.

Total parenteral nutrition (TPN) was given for 8-9 days to 15 prematures and full term neonates (gestational age 26-40 weeks) with respiratory problems or respiratory distress syndrome (RDS). The solutions were administered via peripheral veins during 24 h. Serum electrolytes, calcium, triglycerides and amino acids were measured before and on the 2nd, 4th and 7th day of TPN acid-base balance, blood glucose and serum bilirubin were measured daily and serum transaminases and total protein on the final day of TPN. The total amount of findings administered was 126 ml/kg BW/day and consisted of 10.4 g glucose, 1.9 g fat and 1.95 g amino acids with the total amount of calories reaching an average of 68.7 kcal/kg BW/day (61% glucose, 27.6% fat and 11.4% protein). Three children (2 very small prematures, 1 with severe perinatal asphyxia) died of causes unrelated to TPN. Serum electrolytes, calcium and blood glucose levels were in the normal range in all cases, acid-base balance was affected minimally and moderate hyperbilirubinemia was observed in all neonates. Serum transaminase values were in the normal range as was total protein. Hypertriglyceridemia with values over 3 mmol/l was observed in the very premature neonates and in one neonate with septicemia. Our findings are in favor of administration of MCT fat emulsion to prematures and full term neonates.

[Total parenteral nutrition of premature infants: metabolic effects of an exogenous supply of L-aspartic acid and L-glutamic acid]. / Totale parenterale Ernährung Frühgeborener: Uber die metabolischen Wirkungen exogener Zufuhren von L-Asparaginsäure und L-Glutaminsäure.

Within the scope of clinically indicated total parenteral nutrition of premature infants, a comparative randomized study was performed to examine--by means of nitrogen-balance studies and determination of the free amino acids in the serum--the metabolic effects of absent or parallel intake of 1.140 mumol L-aspartic acid plus 2.160 mumol L-glutamic acid per kg body weight per day in complete L-amino acid solutions with a comparative E/T-ratio and with identical intake of all other nutrients adapted to the requirement. 1. The nitrogen balance level was not affected by the absent or parallel intake of the dicarbonic acids. 2. Intravenous intakes of glycine plus L-serine, which are higher than 2.5 mmol per kg body weight and day, caused statistically significant increased serum concentrations of glycine and L-serine. Such intakes are obviously above the physiologic regulation range. 3. The absent intake of L-aspartic acid and L-glutamic acid resulted in parallel, statistically significant reduced serum concentrations of aspartic acid and asparagine as well as in homeostatic serum concentrations of glutamic acid and glutamine. Despite the only 15-20% higher intake of proline, alanine and arginine under the infusion regimen lacking dicarbonic acids, there was a parallel, statistically significant marked increase in the serum concentrations of proline, alanine, arginine and methionine as well as a statistically significant marked decrease in those of taurine. Under the infusion regimen containing dicarbonic acids exclusively, constant homeostatic serum concentrations of these amino acids as well as of aspartic acid and glutamic acid were measured. 4. A direct or indirect effect of the exogenous supply of L-aspartic acid and/or L-glutamic acid on the homeostasis of aspartic acid and asparagine, on the endogenous turnover of L-alanine and L-proline as well as on the physiologic course of the Krebs-Henseleit cycle and of the "transsulfuration pathway" must be discussed. 5. Since the supply rates of L-aspartic acid plus L-glutamic acid chosen in series 2 (when continuously administered during 24-hour periods) apparently do not cause any disturbance in amino-acid homeostasis, it is established that under the nutritional conditions given this intake lies within the respective physiologic regulation range and therefore is atoxic.

Total parenteral nutrition in pediatrics.

Parenteral nutrition (p.N.) is indicated whenever oral food intake is partly or completely disturbed. The objective of this type of treatments is to provide the organism with sufficient nutrients and maintain the structure and growth. The supply of an optimum mixture of water, protein, carbohydrates, fats, minerals, vitamins and trace elements is a prerequisite for this. In the following parts of this study the indications for p.N., the technique and requirements for different nutrients, minerals, trace elements and vitamins are presented. A type of amino acid mixture especially prepared for pediatric use is prevented and new results of t.p.N. are discussed. In the following parts of this study the indications for p.N., the technique and practice of the infusion programme, the clinical and laboratory investigation of t.p.N., the complications and their prophylaxis during the p.N. are discussed. The goal of better total parenteral nutrition is approached when dosage, infusion rate, contraindications and the guidelines discussed here are observed. We will, however, continue the work for a further improvement of intravenous nutrition.

[Comparison of serum fatty acid patterns in mothers and their newborns (author's transl)]. / Vergleichende Untersuchungen zum Serumfettsäuremuster Gebärender und deren Neugeborener

The fatty acid patterns of total serum lipids in the blood of 15 mothers and the mixed cord blood of their newborns were determined by gaschromatography, and the results compared. It is known that the placenta maintains a concentration gradient for lipids between maternal and fetal blood. Quantitative results are given for the total lipid content of the two compartments. The fetal total lipid content was only about one quarter of the mother's. The fatty acid patterns differed characteristically as well, mainly with regard to the concentration of the essential linoleic and arachidonic acid. The linoleic acid level in the maternal blood was high, but low in the mixed blood of the umbilical cord. This was contrasted by low maternal and high fetal levels of arachidonic acid. The placental fatty acid composition was unusual with a 21% content of arachidonic acid. Feeding of a partially-adapted baby food formula resulted in a gradual rise of linoleic acid levels reaching those of adults at the age of 4-9 months.

[Fatty-acid pattern of serum lipids (standards for mothers, placentas and infants)]. / Zum Fettsäuremuster der Serumlipide (Normwerte für Gebärende, Plazenten und Säuglinge)

The standard distribution of the fatty acids in the total lipids of serum was gaschromatographically defined in the respective umbilical cord blood of 24 mothers and their newborn babies, as well as in 20 placentas. The same examinations were made with 30 newborn babies on the day of birth, 14 children in the newborn stage, 22 young babies between 3 and 10 weeks old and 16 older babies between 4 and 12 months old. In the umbilical cord mixed blood of another collective (n = 10) the separation of the total serum lipids in the individual fatty fractions (neutral lipids, phospholipids, cholesterol esters) was also undertaken. The results were compared and existing differences were discussed. It was further established that an advance towards the adult's fatty acid pattern already takes place at an age between 4 and 12 months.

[The spectrogram of trace elements in newborns and infants]. / Uber das Spektrogramm der Spurenelemente bei Neugeborenen und Säuglingen

In 15 newborn infants and 34 sucklings the spectrogram of 25 cations in whole blood, serum and urine was determined by emission and atomic absorption spectrometry. The values ascertained by this method are tabulated and compared with the mean normal values of adults. Already known basic values are supplemented and the distribution patterns of not yet determined trace elements are demonstrated. Highly significant deviations from the normal values of adults were established in the whole blood of the newborn with regard to zinc, copper and chromium. The same differences became manifest when we compared materanal and infantile whole blood. In serum, on the contrary, no differences were observed. In urine, however, significant differences occured in numerous cations. The sucklings of the 1st trimenon showed highly significant deficits in manganese and copper values in whole blood.

[The fatty acid patterns of infants under conditions of oral nutritions]. / Zum Fettsäuremuster des Säuglings und Kleinkindes unter dem Einfluss oraler Nahrungen

Theinfluence of oral milk foods on the fatty acid pattern of the total serumlipids was examined on 58 healthy infants and small children. It is known that the newborn;s fatty acid pattern is different to that of the adult's. These differences pertain chiefly to the essential linoleic acid and arachidonic acid as well as to the other fatty acids. The time of adaptation to the adult's fatty acid patter was to be ascertained. The result was that a speedy approximation depended on the food used and it's particular fatty acid pattern.

[Amino acid requirements of premature and newborn infants under conditions of parenteral feeding]. / Aminosäurenbedarf Früh- und Neugeborener unter den Bedingungen der parenteralen Ernährung

In pediatric literature there are reported good clinical results after administration of nearly all hitherto tested amino acid solutions despite their different composition. In a first series of experiments on 10 premature infants with a commercial amino acid solution, which was developed for adults, there occurred--despite good tolerance and positive nitrogen balance--distinct disturbances in methionine, phenylalanine, tyrosine, proline, glycine, serine and alanine homeostasis. These disturbances nearly reached the extent of inborn errors of amino acid metabolism. It, therefore, seemed necessary to develop an optimal amino acid solution for parenteral nutrition of premature and newborn infants. There followed a second series of experiments on 5 infants with a correspondingly changed amino acid pattern, a third and a fourth one. By an experimental examination, which was carried out in 80 orally fed infants, normal serum values were determined. On the basis of the findings obtained in the course of these examinations and under consideration of well-known requirement rates determined in oral nutrition it was possible to develop an amino acid solution with highly reduced metabolic risk. At the same time the physiological regulation range of some amino acids could be clarified satisfactorily. By this the significance of tyrosine, proline and possibly glycine as essential amino acids for the young infancy was proved. Further examinations on lysine and leucine metabolism are being carried out.