Comparison of the physical health in adult patients with phenylketonuria (PKU) and healthy age matched controls [Elektronische Ressource] / vorgelegt von Juliana Thamar Freiin von Berlepsch

Juliana Freiin Von Berlepsch

Sujets

• Gesundheit

Informations

• Publié par: ludwig-maximilians-universitat_munchen
• Publié le: 01 janvier 2009
• Nombre de lectures: 36
• Langue: Deutsch
• Poids de l'ouvrage: 10 Mo

Extrait

Aus der Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital
der Ludwig-Maximilians-Universität München
Direktor: Professor Dr. med. D. Reinhardt









Comparison of the physical health
in adult patients with phenylketonuria (PKU)
and healthy age-matched controls










Dissertation
zum Erwerb des Doktorgrades der Humanbiologie
an der Medizinischen Fakultät der
Ludwig-Maximilians-Universität zu München











vorgelegt von
Juliana Thamar Freiin von Berlepsch
aus
Mittweida
2009
Mit Genehmigung der Medizinischen Fakultät
der Universität München










Berichterstatter: Professor Dr. med. Berthold Koletzko


Mitberichterstatter: Prof. Dr. Thomas Lang
Prof. Dr. Yoon S. Shin-Podskarbi


Mitbetreuung durch den
promovierten Mitarbeiter: Dr. agr. J. Demmelmair


Dekan: Prof. Dr. med. Dr. h. c. M. Reiser, FACR, FRCR


Tag der mündlichen Prüfung: 25.05.2009


Index of contents Page
1 Introduction .............................................................................................................1
1.1 Definition of phenylketonuria ............................................................................... 2
1.2 Clinical symptoms of phenylketonuria ................................................................ 3
1.3 Biochemistry of phenylketonuria ......................................................................... 4
1.4 Diagnosis of phenylketonuria 6
1.5 Therapy of phenylketonuria in general 7
1.6 Therapy of phenylketonuria in adulthood ........................................................... 9
1.7 Aims of the study................................................................................................. 17
2 Materials and Methods .........................................................................................18
2.1 Subjects and study design.................................................................................. 18
2.2 Study procedure................................................................................................... 18
2.2.1 Clinical investigation..............................................................................................................19
2.2.2 Neurophysiologic testings .....................................................................................................20
2.2.3 Neurostructural testing..........................................................................................................21
2.2.4 Neuropsychological testings .................................................................................................22
2.2.5 Nutritional, cardiovascular and metabolic status ..................................................................24
2.2.6 Analysis of blood samples ....................................................................................................25
2.2.6.1 Analysis of fatty acid profile in plasma phospholipids.......................................................... 30
2.2.6.2 Analysis of vitamin A and E in plasma................................................................................. 33
2.3 Data management and statistical analyses....................................................... 36
2.4 Ethical aspects and insurance............................................................................ 37
3 Results ...................................................................................................................38
3.1 Subjects ................................................................................................................ 38
3.2 Nutritional status of the patients........................................................................ 39
3.2.1 Measurement of fatty acids in plasma phospholipids ...........................................................39
3.2.2 Vitamin A and E in plasma....................................................................................................41
3.2.3 Dietary intake and nutritional supply.....................................................................................42
3.2.4 Comparison of the nutrition data with data from patients followed at Münster.....................49
3.3 Immune status of the patients ............................................................................ 53
3.4 Cardiovascular risk of the patients .................................................................... 56
3.5 Metabolic status of the patients ......................................................................... 59
3.6 Neurological status of the patients 62
3.6.1 Neurophysiological testings ..................................................................................................62
3.6.2 Neurostructural testing..........................................................................................................65
3.6.3 Neuropsychological tests ......................................................................................................67
3.7 Subjetcs’ own assessment of their health......................................................... 71
4 Discussion.............................................................................................................72
4.1 Subjects ................................................................................................................ 72
4.2 Nutritional status.................................................................................................. 73
4.3 Immune status...................................................................................................... 78
4.4 Cardiovascular risk.............................................................................................. 79
4.5 Metabolic status................................................................................................... 81
4.6 Neurological status 82
4.6.1 Neurophysiological findings ..................................................................................................82
4.6.2 Neurostructural findings ........................................................................................................83
4.6.3 Neuropsychological findings .................................................................................................84
4.7 Subjective assessment of health status............................................................ 87
5 Summary................................................................................................................89
6 Zusammenfassung ...............................................................................................91
7 Attachment ............................................................................................................93
7.1 Tables.................................................................................................................... 93
7.2 Figures .................................................................................................................. 98
7.3 Used information and documentation materials............................................... 99
7.4 Acknowledgements ........................................................................................... 145
7.5 Publication of the obtained data....................................................................... 146
8 References…………………………………………………………………………......147
9 Curriculum vitae…….…………………………………………………………….......158

Index of abbreviations

1%A extinction coefficient 1cm
AA arachidonic acid
AAS atomic absorption spectrometry
Apo A1 apolipoprotein A1
Apo B in B
APS Working Group on Paedriatric Metabolic Disorders
AVLT auditory verbal learning test
BH tetrahydrobiopterine 4
BHT butylated hydroxytoluene
BMI body mass index
BMR basal metabolic rate
CV coefficient of variation
CWIT colour word interference test
DHA docosahexaenoic acid (22:6n-3)
DGE German Nutrition Society
EDTA ethylene diamine tetraacetic acid
ELISA enzyme-linked immunosorbent assay
EPA eicosapentaenoic acid (20:5n-3)
FAME fatty acid methyl esters
Fig. figure
GC gas chromatography
HDL high-density lipoprotein
HPA hyperphenylalaninemia
HPLC high performance liquid chromatography
IQR interquartil range (25.- 75. percentiles)
IS internal standard
LCPUFA long-chain polyunsaturated fatty acid
LDL low density lipoprotein
Lp (a) lipoprotein (a)
MPT motor performance task
MPKUC maternal phenylketonuria collaborative study
MUFA monounsaturated fatty acids
NCT number combination test
NEFA non-esterified fatty acids
NIST national institute of standards and technology
PAL physical activity level
Phe phenylalanine
PKU phenylketonuria
PUFA polyunsaturated fatty acids
SFA saturated fatty acids
SD standard deviation
SEM standard error of the mean
Tab. table
TC total cholesterol
TFA trans fatty acids
TG triglycerides
TLC thin layer chromatography