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1.
J Hum Genet ; 63(6): 707-716, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29618761

ABSTRACT

Seven subunits of the mitochondrial contact site and cristae junction (CJ) organizing system (MICOS) in humans have been recently described in function and structure. QIL1 (also named MIC13) is a small complex that is crucial for the maintenance and assembling of MICOS. A novel mutation of an essential splice site in the C19orf70 gene encoding QIL1 induces severe mitochondrial encephalopathy, hepatopathy and lactate acidosis consistent with psychomotor retardation. In addition, bilateral kidney stones were observed. Disassembly of MICOS complex subunits displays lack of MIC10-MIC26-MIC27-QIL1 subcomplex, resulting in aberrant cristae structure and a loss of cristae junctions and contact sites. In liver and muscle tissue, the activity of the respiratory chain complexes (OXPHOS) was severely impaired. Defects in MICOS complex do not only affect mitochondrial architecture, but also mitochondrial fusion, metabolic signalling, lipid trafficking and cellular electric homeostasis.


Subject(s)
Genes, Lethal , Liver Diseases/genetics , Membrane Proteins/genetics , Mitochondria/metabolism , Mitochondrial Encephalomyopathies/genetics , Mitochondrial Proteins/genetics , Mutation , Psychomotor Performance , Acidosis, Lactic/complications , Brain/diagnostic imaging , Electron Transport , Fatal Outcome , Female , Humans , Infant , Infant, Newborn , Kidney Calculi/complications , Liver/metabolism , Liver Diseases/complications , Liver Diseases/physiopathology , Magnetic Resonance Imaging , Mitochondrial Encephalomyopathies/complications , Mitochondrial Encephalomyopathies/diagnostic imaging , Mitochondrial Encephalomyopathies/physiopathology , Muscles/metabolism , Open Reading Frames , Oxidative Phosphorylation , RNA Splice Sites
2.
JIMD Rep ; 26: 21-9, 2016.
Article in English | MEDLINE | ID: mdl-26238249

ABSTRACT

Congenital disorders of glycosylation form a rapidly growing group of inherited metabolic diseases. As glycosylation affects proteins all over the organism, a mutation in a single gene leads to a multisystemic disorder. We describe a patient with TMEM165-CDG with facial dysmorphism, nephrotic syndrome, cardiac defects, enlarged cerebral ventricles, feeding problems, and neurological involvement. Having confirmed the diagnosis via prenatal diagnostics, we were able to observe the glycosylation right from birth, finding a pathological pattern already on the first day of life. Within the next few weeks, hypoglycosylation progressed to less sialylated and then also to hypogalactosylated isoforms. On the whole, there has not been much published evidence concerning postnatal glycosylation and its adaptational process. This is the first paper reporting changes in glycosylation patterns over the first postnatal weeks in TMEM165-CDG.

3.
J Inherit Metab Dis ; 38(5): 931-40, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25778940

ABSTRACT

Congenital disorders of glycosylation (CDG) are a group of hereditary metabolic diseases characterized by abnormal glycosylation of proteins and lipids. Often, multisystem disorders with central nervous system involvement and a large variety of clinical symptoms occur. The main characteristics are developmental delay, seizures, and ataxia. In this paper we report the clinical and biochemical characteristics of a 5-year-old girl with a defective galactosylation of N-glycans, resulting in developmental delay, muscular hypotonia, epileptic seizures, inverted nipples, and visual impairment. Next generation sequencing revealed a de novo mutation (c.797G > T, p.G266V) in the X-chromosomal gene SLC35A2 (solute carrier family 35, UDP-galactose transporter, member A2; MIM 300896). While this mutation was found heterozygous, random X-inactivation of the normal allele will lead to loss of normal SLC35A2 activity in respective cells. The functional relevance of the mutation was demonstrated by complementation of UGT-deficient MDCK-RCA(r) and CHO-Lec8 cells by normal UGT-expression construct but not by the mutant version. The effect of dietary galactose supplementation on glycosylation was investigated, showing a nearly complete normalization of transferrin glycosylation.


Subject(s)
Congenital Disorders of Glycosylation/genetics , Congenital Disorders of Glycosylation/therapy , Monosaccharide Transport Proteins/genetics , Animals , CHO Cells , Child, Preschool , Cricetinae , Cricetulus , DNA Mutational Analysis , Dogs , Female , Galactose/therapeutic use , Humans , Madin Darby Canine Kidney Cells , Monosaccharide Transport Proteins/deficiency , Phenotype
4.
Dtsch Med Wochenschr ; 129(3): 75-81, 2004 Jan 16.
Article in German | MEDLINE | ID: mdl-14724780

ABSTRACT

BACKGROUND AND OBJECTIVE: Disease management programs (DMP) e. g. for diabetes mellitus, should be the clinical and economic basis for a structured treatment. This article shows results of specialized outpatient treatment using a risk factor depending patient classification. PATIENTS AND METHODS: Diabetes associated co-morbidities, micro- and macrovascular complications, the results and findings of blood pressure and metabolism of glucose and lipids, as well as all treatment-associated costs of 5245 type 2 diabetics were collected for a period of 12 months, accompanied by different measures of quality control. For documentation in the centres, all available original data were used as local data sources. RESULTS: The patient classification system, on which diabetic risk profiles are based, covered 74.3 % of all type 2 diabetic patients. Daily direct costs for all treatment measures ranged between EUR 4.79 (primary prevention) and EUR 8.96 for patients suffering from advanced diabetic foot syndrome. Most of the treatment costs arose from prescriptions of pharmaceuticals, other remedies and aids. Specific strategies of therapy were both related to the severity of co-morbidities and the time since manifestation of diabetes (r = 0.486; p < 0.01, two-sided). The share of patients receiving diet and exercise only decreased from 22.8 % (primary prevention) to below 10 % of patients suffering from microvascular complications. Simultaneously, the share of patients receiving insulin increased up to 81.8 % of patients suffering from advanced diabetic retinopathy. CONCLUSION: The risk profile specific variation in the results clearly shows the need of a risk factor depending classification system for type 2 diabetes, which could be useful to reform and focus the system of compensating payments between health insurance companies more and more on morbidity, or on risk profiles.


Subject(s)
Diabetes Mellitus, Type 2/classification , Diabetes Mellitus, Type 2/therapy , Disease Management , Health Care Costs , Adult , Aged , Comorbidity , Diabetes Mellitus, Type 2/economics , Diabetes Mellitus, Type 2/epidemiology , Diabetic Angiopathies/economics , Diabetic Angiopathies/epidemiology , Diabetic Angiopathies/therapy , Diabetic Foot/economics , Diabetic Foot/epidemiology , Diabetic Foot/therapy , Diabetic Retinopathy/economics , Diabetic Retinopathy/epidemiology , Diabetic Retinopathy/therapy , Female , Germany/epidemiology , Humans , Hypoglycemic Agents/economics , Hypoglycemic Agents/therapeutic use , Insulin/economics , Insulin/therapeutic use , Male , Middle Aged , Prevalence , Primary Prevention/economics , Risk Assessment/economics , Risk Factors
5.
Acta Paediatr ; 83(12): 1282-6, 1994 Dec.
Article in English | MEDLINE | ID: mdl-7734871

ABSTRACT

Reference values for tubular transport of sodium, phosphate, glucose and amino acids are generally based on inulin or creatinine short-term clearances, which are difficult to obtain in children. Hence, quantitative assessment of tubular transport capacities is rarely performed. For a simplified procedure, reference values for fractional sodium excretion, phosphate reabsorption related to glomerular filtration rate, percent glucose and percent amino acid reabsorption were established in 62 children from spot urine and simultaneously obtained blood samples. Sodium excretion, and glucose and amino acid reabsorption were significantly lower in infants than children, whereas phosphate reabsorption decreased during the first year of life. Results using the proposed protocol and those obtained from timed urine specimens correlated well; the phenomenon of renal adaptation during childhood could equally well be demonstrated. Renal tubular dysfunction can be diagnosed without timed urine specimens.


Subject(s)
Amino Acids/urine , Blood Glucose/metabolism , Child Development/physiology , Kidney Tubules/physiology , Phosphates/urine , Sodium/urine , Absorption/physiology , Adolescent , Child , Child, Preschool , Female , Glomerular Filtration Rate/physiology , Humans , Infant , Infant, Newborn , Kidney Function Tests , Male , Reference Values , Renal Tubular Transport, Inborn Errors/diagnosis , Renal Tubular Transport, Inborn Errors/urine
6.
Memory ; 1(3): 185-9, 1993 Sep.
Article in English | MEDLINE | ID: mdl-7584266

ABSTRACT

This paper discusses the evidence on the confidence-accuracy relationship in eyewitness research. It is pointed out that the conclusion often drawn on the basis of such research, that there is little or no relationship between eyewitness confidence and accuracy, is an unwarranted generalisation based on the use of experimental paradigms that are limited in terms of their generalisability to courtroom situations. In particular, almost all studies involve between-subject rather than within-subject designs, thereby limiting the generalisability of findings. A within-subjects analysis examines whether, within an individual, more confident responses are associated with greater accuracy than are less confident responses. A between-subjects analysis examines whether a more confident individual is likely to be more accurate than a less confident individual. A further limitation on the generalisability to real life situations of studies conducted to date is that experiments must involve making errors in identification in order to allow correlational analysis to take place. This means that findings cannot be generalised to those real life situations where all subjects are likely to be completely accurate and confident.


Subject(s)
Jurisprudence , Memory , Research Design , Humans , Judgment , Reproducibility of Results
7.
Neuropediatrics ; 23(5): 257-9, 1992 Oct.
Article in English | MEDLINE | ID: mdl-1454145

ABSTRACT

In an infant with typical pyridoxine-dependent seizures, CSF GABA level, was determined before treatment with pyridoxine. Before onset of treatment, level of GABA in CSF was highly lowered (16 pmol/ml), pyridoxine level in serum was within normal range. Immediately after application of 80 mg pyridoxine fits stopped and the EEG was without seizure activity. The data substantiate previous findings in brain tissue from a patient with pyridoxine-dependent seizures. They are proof of a disturbed GABA metabolism in pyridoxine dependent seizures.


Subject(s)
Pyridoxine/metabolism , Seizures/metabolism , gamma-Aminobutyric Acid/metabolism , Brain/metabolism , Chromosomes, Human, Pair 2 , Glutamate Decarboxylase/biosynthesis , Humans , Infant , Infant, Newborn , Injections, Intravenous , Male , Protein Binding/genetics , Pyridoxine/adverse effects , Pyridoxine/therapeutic use , Seizures/drug therapy , gamma-Aminobutyric Acid/biosynthesis , gamma-Aminobutyric Acid/cerebrospinal fluid
8.
Genomics ; 12(1): 80-8, 1992 Jan.
Article in English | MEDLINE | ID: mdl-1370812

ABSTRACT

The laboratory mouse C57BL genome contains about 50 copies of a long-range repeat DNA family clustered in the C-D region of chromosome 1. The repeat length is more than 50 kb and includes sequences homologous to at least two mRNAs. There are small differences in the copies of this repeat family such as restriction site mutations and gross differences like rearrangements and insertions of LINE1 elements. A germline homogeneously staining region occurring as a chromosome 1 polymorphism in many feral populations of the house mouse is an amplified version of this long-range repeat cluster.


Subject(s)
Repetitive Sequences, Nucleic Acid , Animals , Blotting, Southern , Cloning, Molecular , DNA Probes , Deoxyribonucleases, Type II Site-Specific/metabolism , Electrophoresis, Gel, Pulsed-Field , Gene Amplification , Genome , Germ Cells , Mice , Mice, Inbred C57BL , Muridae , Polymorphism, Restriction Fragment Length , Restriction Mapping , Sequence Homology, Nucleic Acid , Staining and Labeling
9.
Injury ; 11(1): 3-9, 1979 Aug.
Article in English | MEDLINE | ID: mdl-391714

ABSTRACT

If a viable kidney transplant programme is to be continued on a national basis, many of the problems at present surrounding organ transplantation must be tackled urgently. This paper discusses the psychological and emotional problems which are presently seen to hinder a successful renal transplantation policy, and considers the relative advantages and disadvantages of the kidney donor card scheme.


Subject(s)
Kidney Transplantation , Tissue Donors/psychology , Attitude of Health Personnel , Humans , Jurisprudence , Legislation, Medical , Renal Dialysis/economics , Transplantation, Homologous , United Kingdom
12.
Acta Psychol (Amst) ; 31(3): 293-6, 1969 Oct.
Article in English | MEDLINE | ID: mdl-5366463
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