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E Mönch

Publications and source records attributed to E Mönch.

At least 19 recordsLinked to original sources
PubMed2001

Phenotypic heterogeneity and adverse effects of serine treatment in 3-phosphoglycerate dehydrogenase deficiency: report on two siblings.

Clinical experience with the treatment of 3-phosphoglycerate dehydrogenase deficiency, a rare inherited disorder of serine synthesis, is scarce. We report on two sisters with phenotypic heterogeneity and a favourable response to combined serine and glycine supplementation. The elder sibling was found to be normocephalic at birth and showed moderate delay of white matter myelinisation, while her seizures arrested spontaneously even without treatment. In the younger sister with the classical phenotype, feeding difficulties with recurrent gastro-oesophageal reflux prompted us to treat her temporarily with high-dose serine (1400 mg/kg/day). An arrest of head growth then occurred but could be reversed by reducing the serine supply. In both children serine therapy was associated with decreased concentrations of methionine, isoleucine, and ornithine in the cerebrospinal fluid, attributed to competitive inhibition of neutral amino acid transport across the blood-brain barrier. In contrast to reports in the literature, these findings demonstrate that congenital microcephaly, intractable seizures, and dysmyelinisation are not invariably present in patients with 3-phosphoglycerate dehydrogenase deficiency. An adverse effect of high-dose serine therapy on head growth and on the transport of neutral amino acids across the blood-brain barrier should be considered and requires adjustment of treatment.

Amino Acids↗
PubMed2001

Experimental evaluation of a cell module for hybrid liver support.

Aim of the study was to evaluate a hybrid liver support system in a porcine model of acute liver failure, after hepatectomy. Pigs with a body weight of 70+/-18 kg underwent total hepatectomy and porto-cavo-caval shunting as well as ligation of the bile duct and the hepatic artery. Control animals were connected to the system (including capillary membrane plasma separation) containing a four compartment bioreactor with integral oxygenation and decentralized mass exchange but without liver cells. The treatment group received hybrid liver support with the same system including 370+/-42 g primary isolated porcine parenchymal liver cells in co-culture with hepatocyte nursing cells, tissue engineered to liver- like structures at high density. Treatment started after complete recovery from anesthesia and was performed continuously. A positive influence on peripheral vascular resistance and a reduced need of catecholamine dosage was observed in the treatment group. Hybrid liver support with a cell module upscaled for clinical application significantly prolonged survival time in animals after hepatectomy with the longest survival being 26 hours in the control group an 57 hours in the treatment group.

Animals↗
PubMed2000

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.

Amino Acid Substitution↗
PubMed1999

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.

Adolescent↗
PubMed1999

HFE gene mutation and transferrin saturation in very low birthweight infants.

AIM: To determine if there is an association between high transferrin saturation and the C282Y HFE gene mutation in very low birthweight (VLBW) infants. METHODS: One hundred and forty three VLBW infants receiving recombinant erythropoietin and 3 to 9 mg/kg/day of enteral iron were studied. Genomic DNA was extracted from filter paper cards. The C282Y mutation was determined by restriction fragment length polymorphism analysis. RESULTS: Six infants were heterozygous for the mutation; none was homozygous. Ten infants had a transferrin saturation above 80% at least once. No infant was positive for both transferrin saturation above 80% and the mutation. CONCLUSIONS: The data strongly suggest that there is no association between high transferrin saturation and the HFE gene mutation in VLBW infants during the first weeks of life.

Female↗
PubMed1998

Diurnal changes in plasma amino acids in maple syrup urine disease.

Protein turnover is a cyclic process with a net loss of protein in the (catabolic) fasted state and a net gain in the (anabolic) fed state. In maple syrup urine disease (MSUD) the early block of degradation of the branched-chain amino acids (BCAA) brings about the opportunity for evaluation of the diurnal variation in net protein anabolism and catabolism by studying cyclic changes in the plasma concentrations of BCAA. The alterations in plasma BCAA in a 3-y-old boy with classical MSUD were studied in the fed and fasted state over a period of 19 months. For each amino acid a total of 34 data pairs was calculated. The plasma concentrations of the BCAA leucine, valine and isoleucine were constantly higher in the fasted than in the fed state. Plasma concentrations of alloisoleucine, being a non-protein amino acid, did not participate in cyclic changes. In contrast, the essential amino acid pair tyrosine and phenylalanine increased after meals. The fasting concentration of alanine increased after feeding, while glycine did not change significantly. Healthy subjects show a decrease in all amino acids in the fasted (mild catabolic) state and an increase in the fed state. These findings in MSUD suggest a net decrease in non-BCAA as result of a greater rate of amino acid oxidation rate than of protein breakdown and a net entry of BCAA into plasma in the fasted state due to the specific metabolic block. Such changes in amino acid plasma pools have to be taken into account during monitoring of treatment and especially when in vivo leucine oxidation is assessed.

Amino Acids↗
PubMed1996

Utilisation of amino acid mixtures in adolescents with phenylketonuria.

The nutritional regimen of patients with phenylketonuria (PKU) comprises a diet of natural proteins and phenylalanine (Phe)-free amino acid (AA) mixture. The main daily protein requirement is covered by a Phe-free AA mixture. In an adult with PKU, the consumption of the daily AA requirement in one single dose at breakfast caused nausea and vomiting. Therefore, four studies were designed to investigate the adverse and metabolic effects resulting from large intakes of AA mixtures used in the treatment of PKU patients with respect to the following: (1) biochemical effects following consumption of one single dose of Phe-free AA mixture in healthy persons; (2) transient metabolic changes caused by different individual regimens of AA intake in healthy persons and in one PKU patient; (3) nitrogen excretion in PKU patients taking the AA mixture in two or three portions; and (4) catabolic metabolism of AA in a PKU patient. In healthy subjects following the ingestion of the AA mixture in one bolus there was an increase in the blood levels of the given AA and also an increase in blood insulin concentration and a decrease in blood glucose concentration. These changes were less marked when the AA mixture was divided into three portions per day. In contrast, in a PKU patient following the ingestion of AA there was an increase in blood glucose. The urinary nitrogen excretion was greater in PKU patients when one compared to three portions of AA mixture was taken. The consumption of the daily requirement of AA mixture in one single does produced increased catabolism in a PKU patient. In conclusion it is recommended that the total daily amount of AA mixture should be divided into a minimum of three portions.

Adolescent↗
PubMed1994

Dependence of the utilization of a phenylalanine-free amino acid mixture on different amounts of single dose ingested. A case report.

For patients with phenylketonuria the daily ingested phenylalanine-free amino acid mixture is the most important source of nitrogen. It is recommended to ingest one third of the total amount combined with main meals. Some patients, especially the older ones, do not follow this recommendation; they ingest the entire daily amount of amino acid mixture in one portion. This intake mode leads to an increased oxidative utilization of the amino acids. To set up an example for this metabolic phenomenon, a 13C-leucine breath test was performed in one female phenylketonuric patient. She ingested a third of her daily amount of the amino acid mixture combined with an oral tracer of 3 mg 13C-leucine/kg body weight at breakfast. The breath test was carried out by a standardized time schedule over 5 h. Three days later the breath test was repeated when she ingested the total amount of amino acid mixture in only one portion at breakfast. Total daily caloric intake and food composition were not changed. On both days a 24 h urine was collected to determine total nitrogen loss. The 13C-content of expired air was analysed by gas isotope ratio mass spectrometry, the total nitrogen content was determined using a combustion unit. The 13C-elimination rate as a percentage of the applied 13C-tracer was 9.5% on the first test day as compared to 19.6% on the 2nd day. The corresponding total nitrogen excretion was increased (4.3-6.9 g/24 h).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Clinical features and diagnostic approach in type I tyrosinaemia in an infant with cytomegaly virus infection and bacterial sepsis.

A severely ill 2-month-old female infant was admitted with meningitis and septicaemia caused by Streptococcus pneumoniae. The patient, who also had an acute cytomegalovirus (CMV) infection, revealed the typical clinical and biochemical characteristics of type I tyrosinaemia (TIT). Clinical evidence of severe hepatocellular damage was shown, but urinary succinylacetone was not detected. The diagnosis of TIT was finally confirmed by decreased activity of fumarylacetoacetase (FAA) in skin fibroblasts from the patient and both parents. Following dietary treatment and after overcoming the bacterial and viral infection, the patient's liver function improved.

Acute Disease↗
PubMed1993

Gastroenteropancreatic neuroendocrine tumours contain a common set of synaptic vesicle proteins and amino acid neurotransmitters.

Human neuroendocrine tumours of the gastroenteropancreatic system contain major integral membrane proteins of small synaptic vesicles of neurons, together with characteristic membrane polypeptides of large dense-core vesicles of neurons and neuroendocrine cells. The membrane polypeptides characteristic for small synaptic and large dense-core vesicles are detected in pheochromocytomas (n = 6), functional (n = 6) and non-functional (n = 6) foregut, and midgut carcinoids (n = 17). All gastroenteropancreatic tumours contain large amounts of amino acid neurotransmitters, i.e. glycine and glutamate. gamma-Aminobutyric acid, however, is only found in some foregut carcinoids. Thus, neuroendocrine gastroenteropancreatic tumours possess a vesicle type with a content and membrane composition similar to small synaptic vesicles of neurons.

Animals↗
PubMed1991

[Phenylalanine-free amino acid mixture: metabolic effects in relation to a single dose].

In the dietetic treatment of phenylketonuric patients phenylalanine free amino acid mixtures are given to meet the protein requirement of the patient. In four healthy probands we tested the metabolic effects of four different PKU-preparations given in variable amounts ingested with carbohydrate and fat containing meals. We determined glucose, insulin, amino acids, and urea in blood. Following the amino acid load we saw an increased insulin output with a hypoglycemic reaction or, with smaller amounts a lack of the normal postprandial blood glucose increase. Hyperaminoacidemias depended on the amount of amino acids ingested. The increase of blood urea found suggests that part of the amino acids were degraded. To compare the results we studied a PKU-patient. He showed corresponding but milder effects.

Adult↗
PubMed1990

[Medium-chain acyl-CoA dehydrogenase defect. Acute cerebral episodes and nonketotic hypoglycemia in children].

A four-year-old and a three-year-old boy with somnolence, coma and hypoglycaemia were found to have a defect in the beta-oxidation of medium-chain fatty acids (medium-chain acyl CoA dehydrogenase [MCAD] defect). The brother of one of them had died aged 16 months of an acute disease resembling Reye's syndrome (coma, fatty liver, cerebral oedema). The other two boys have no symptoms now under daily treatment with 100 mg/kg carnitine and frequent carbohydrate-high, fat-poor meals. The MCAD defect is inherited as an autosomal recessive trait and should be considered in the differential diagnosis of unexplained loss of consciousness in children with non-ketotic hypoglycaemia or with Reye's syndrome, as well as in families with sudden infant death.

Acyl-CoA Dehydrogenase↗
PubMed1990

Examination of urine metabolites in the newborn period and during protein loading tests at 6 months of age--Part 1.

In the course of the collaborative study of children treated for PKU, urine samples from a total of 165 patients were analysed at six different times: in the newborn period before onset of therapy, after beginning of dietary management, during and immediately after a protein loading test at 6 months of age. In 95.9% of newborns with elevated Phe levels in plasma, metabolites of this amino acid as well as of Tyr could be detected. Of all metabolites phenylpyruvate always showed the highest concentration, followed by phenyllactate and o-hydroxy-phenylacetate. During the protein loading test an increase of the same metabolites occurred. At the age of 6 months the percentage of p-hydroxylated compounds related to the sum of all metabolites was lower than in the newborn period. Comparing the results of urine analyses at 6 months of age after the protein loading tests with the classification of HPA into the reaction types I-III, it can be clearly stated that patients with the milder forms II and III have already lower levels of Phe metabolites in urine before onset of therapy compared to the reaction type I. In retrospect 52% of the newborns could therefore be classified as reaction type I even before beginning of dietary management. The analysis of urinary Phe metabolites before the onset of therapy therefore provides sufficient information about the reaction type.

Creatinine↗
PubMed1989

Haplotype analysis of the phenylalanine hydroxylase gene in Turkish phenylketonuria families.

We have estimated the haplotype distribution of mutant and normal phenylalanine hydroxylase (PAH) alleles for 17 Turkish phenylketonuria (PKU) families: 20 normal and 27 mutated PAH alleles could be identified. Of the latter, the most prevalent were associated with haplotype 6 (29.6%), 1 (18.5%) and 36 (11.1%), while the normal alleles were preferentially associated with haplotype 1 (20%). Of the 19 different haplotypes observed, 5 have not been described previously. The haplotype distribution differed significantly from that of the Northern European population. Two of the eight polymorphic sites were in association with PKU. No deletions of exon sequences were found in the families analysed.

Alleles↗