Cerebral sinus occlusion in a boy presenting with asparaginase-induced hypertriglyceridemia.

Cerebral sinus thrombosis is a rare but severe complication during treatment for acute lymphoblastic leukaemia (ALL). It mostly has been reported during treatment with asparaginase and dexamethasone. Hypertriglyceridemia has - albeit very rarely - also been associated with asparaginase therapy. The combination of cerebral sinus thrombosis and hypertriglyceridemia however, has not yet been reported. Here we describe a 15-year-old boy who presented with clinical symptoms and radiologic findings of a cerebral sinus thrombosis. In addition, a life-threatening hypertriglyceridemia was present. The complication was successfully treated by anticoagulation with low molecular weight heparin and the lipid regulator bezafibrate.

Stability of ketone bodies in serum in dependence on storage time and storage temperature.

The serum concentrations of beta-hydroxybutyrate and acetoacetate as well as the beta-hydroxybutyrate/acetoacetate ratio are important parameters for the differential diagnosis of certain inborn errors of metabolism. Acetoacetate, however, is an unstable compound which becomes rapidly decarboxylated. At a storage temperature of -20 degrees C about 40% of the acetoacetate is lost within 7 days and after 40 days storage at this temperature virtually all of the acetoacetate has become degraded. At -80 degrees C the decomposition of acetoacetate occurs with a much slower rate and only 15% of the initial acetoacetate is lost after 40 days storage. The rate constants for the decarboxylation reaction were found to be (6.4 +/- 2.9) * 10(-5) [min(-1)] at -20 degrees C and (0.4 +/- 0.3) * 10(-5) [min(-1)] at -80 degrees C. In contrast, beta-hydroxybutyrate is very stable during storage and hence should be used as main parameter for the evaluation of ketonemia. If determination of acetoacetate and/or of the beta-hydroxybutyrate/acetoacetate ratio is necessary, an assay immediately after collecting the serum samples is recommended. Otherwise, the serum samples should be frozen as soon as possible and stored at -80 degrees C during transport and storage.

Phenylketonuria and hyperphenylalaninemia in eastern Germany: a characteristic molecular profile and 15 novel mutations.

Phenylketonuria (PKU) is an important error of amino acid metabolism which results in most patients from phenylalanine hydroxylase (PAH) deficiency. PKU displays a marked genotypic heterogeneity both within and between different populations. The aim of this study was to establish the genotypic spectrum of PKU in eastern Germany, and to compare this to the distribution of mutations in western Germany. The study population included 302 patients in 290 families who were followed at treatment centers in Berlin, Leipzig and Jena. The study showed marked genotypic variability with a total of 75 mutations, including 15 that have so far not been described (eleven missense mutations, one splicing mutation, and three small deletions). One of these novel mutations, E183Q, occurred in cis to a R408W mutation. In the non-immigrant eastern German population, the frequency of R408W accounted for 40.1% of the PKU alleles. In the immigrant Turkish population of the former West Berlin, the most prevalent mutation was IVS10-11G>A (57%). There was a marked difference of the genotypic spectrum between the population studied here and the data reported from the western part of the country.

Rationale for the German recommendations for phenylalanine level control in phenylketonuria 1997.

UNLABELLED: Treatment of hyperphenylalaninaemias due to phenylalanine hydroxylase deficiency with a low phenylalanine (Phe) diet is highly successful in preventing neurological impairment and mental retardation. There is consensus that, for an optimal outcome, treatment should start as early as possible, and that strict blood Phe level control is of primary importance during the first years of life, but for adolescent and adult patients international treatment recommendations show a great variability. A working party of the German Working Group for Metabolic Diseases has evaluated research results on IQ data, speech development, behavioural problems, educational progress, neuropsychological results, electroencephalography, magnetic resonance imaging, and clinical neurology. Based on the actual knowledge, recommendations were formulated with regard to indication of treatment, differential diagnosis, and Phe level control during different age periods. The development of the early-and-strictly-treated patient in middle and late adulthood still remains to be investigated. Therefore, the recommendations should be regarded as provisional and subject to future research. Efficient treatment of phenylketonuria has to go beyond recommendations for blood Phe level control and must include adequate dietary training, medical as well as psychological counselling of the patient and his family, and a protocol for monitoring outcome. CONCLUSIONS: Early-and-strictly-treated patients with phenylketonuria show an almost normal development. During the first 10 years treatment should aim at blood Phenylalanine levels between 40 and 240 micromol/L. After the age of 10, blood phenylalanine level control can be gradually relaxed. For reasons of possible unknown late sequelae, all patients should be followed up life-long.

[Effect of dietary measures on body weight and height of children with phenylketonuria in East Germany]. / Einfluss der Diätbedingungen auf Körpergewicht und -grösse bei Kindern mit Phenylketonurie in Ostdeutschland.

Body length and body weight of 90 patients with PKU (48 girls and 42 boys) were compared during the years up to 1990 and thereafter. The patients got Berlophen up to 1990 for at least 3 years, and Milupa PKU or PAM (SHS) for 3 years thereafter. The data were compared with the percentiles according to Prader, the significance was calculated with the Chi2-Test. Body length and weight are significantly reduced during the first decade of life compared with normal population. Body length reaches normal values at the age of 12 years, body weight at 9 years respectively. The change of the diet after the german unification had no influence onto body weight and length. The retardation of body length, however, was more marked in patients with very strict dietary control compared to patients with more often dietary faults. The limited availability of essential nutrients seems to be the cause for the somatic retardation of the patients with PKU in the eastern part of germany.

Results of selective screening for inborn errors of metabolism in the former East Germany.

Since the early 1970s selective screening for inherited metabolic disorders has been performed in larger children's hospitals or metabolic centres of the former East-Germany. As a rule the following methods were employed: initially paper chromatography, drop, dip and spot tests, later on thin-layer chromatography and more recently enzyme analysis, gas chromatography, mass spectrometry and HPLC. Normally urine, blood or leucocytes were investigated. The diagnoses were confirmed in metabolic centres in Greifswald, Berlin or Leipzig or in collaboration with specialized laboratories abroad. About 130,000 subjects from former East Germany as well as from different East European countries were investigated, of which 365 patients were diagnosed and classified into roughly 40 various metabolic diseases. The proportion of positive diagnoses was 1 in 400.

[Hemoglobin A1 in hypoglycemias in childhood]. / Hämoglobin A1 bei Hypoglykämien im Kindesalter.

The average HbA1 concentrations of 20 patients with hypoglycaemic diseases were not significantly different from metabolically healthy controls. There was also no correlation between the HbA1 and the blood glucose levels of these patients. Remarkably, two patients which responded to therapy with an increase of blood glucose showed also an increase of HbA1.

Biochemical and clinical observations in four patients with fructose-1,6-diphosphatase deficiency.

Three boys and one girl suffering from inherited fructose-1,6-diphosphatase (FDPase) deficiency are reported. All four patients had less than 25% residual hepatic FDPase activity. While in two out of three patients the enzyme deficiency was also expressed in leucocytes, one patient had a normal enzyme activity. Remarkably, three patients had pronounced neonatal hyperbilirubinaemia requiring exchange transfusion.

[Effect of dietary non-compliance on development in phenylketonuria--studies of 14-year-old patients]. / Einfluss der Diätlockerung auf die Entwicklung bei PKU--Untersuchungen bei 14 Jahre alten Patienten.

25 children with early treated PKU were studied at the age of 14 years. The IQ was higher at the age of 6-8, 10 and 14 years if the dietary control was good (75% of the control values up to 10 mg/dl) compared to children with poor control. The IQ however decreased up to the age of 14 years in both groups. Discontinuation of the diet in children with a good dietary control at the age of 6 years because of a normal EEG after phenylalanine loading causes a decrease of the IQ from 100 at 6 years to 90 at 10 years. The IQ remains stable thereafter up to 14 years. The IQ ist lower at the age of 7 or 8 years in those children in whom the discontinuation of diet is delayed because of abnormal EEG after phenylalanine loading at the age of 6 years, but remains stable up to the age of 14. According to these results a discontinuation of the diet at the age of 6 years can not be recommended even if the EEG is normal after phenylalanine load.

[Results, problems and consequences of early treatment of phenylketonuria]. / Ergebnisse, Probleme und Konsequenzen der Frühbehandlung der Phenylketonurie.

Screening of PKU was started in GDR by means of a napkin-test in 1967 and by Guthrie-test in 1971. A normal development is possible if treatment is started within the first 3 months of life and if the dietary control is good. Maintenance of a dietary control becomes difficult with growing age. The diet, however, should strictly be kept up to the age of 8 to 10 years. Thereafter there should be a low protein nutrition possible with supplementation of tyrosine. Prenatal diagnosis, which is possible in most of the families by RFLP technique, is justified despite the good results because of the social impact onto the family caused by the treatment. Treatment again must be started before pregnancy and must strictly be kept up to birth to avoid fetal damage by maternal PKU.