Fernandes / Saudubray / Berghe Inborn Metabolic Diseases

Diagnosis and Treatment
4th, revidierte Auflage 2006
ISBN: 978-3-540-28785-8
Verlag: Springer
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 561 Seiten, Web PDF

Reihe: Medicine

This classical textbook has become indispensable for those in the front line dealing with metabolic disorders. This 4th edition has been thoroughly updated and revised. The main feature of the book is the strong emphasis on clinical presentation and treatment in acute and chronic situation. One new chapter on Neonatal screening by tandem MS/MS has been added and several new groups of disorders have been included. The first chapter presents the clinical approach to inherited metabolic disease using many algorithms and tables and has been entirely revised and extended to include adult metabolic medicine. It now incorporates many new findings. This accessible and practical book can be used either by going directly to the relevant chapter when the diagnosis is already suspected or by referring to Chapter 1 if it is unknown. Despite numerous updates the book has been maintained at a reasonable size and is published as a single volume of approximately 550 pages divided into 43 Chapters.

Zielgruppe

Professional/practitioner

Autoren/Hrsg.

Fernandes, John

Saudubray, Jean-Marie

Berghe, Georges van den

Walter, John H.

Inhaltsverzeichnis

Diagnosis and Treatment: General Principles.- A Clinical Approach to Inherited Metabolic Diseases.- Newborn Screening for Inborn Errors of Metabolism.- Diagnostic Procedures: Function Tests and Postmortem Protocol.- Emergency Treatments.- Treatment: Present Status and New Trends.- Disorders of Carbohydrate Metabolism.- The Glycogen Storage Diseases and Related Disorders.- Disorders of Galactose Metabolism.- Disorders of the Pentose Phosphate Pathway.- Disorders of Fructose Metabolism.- Persistent Hyperinsulinemic Hypoglycemia.- Disorders of Glucose Transport.- Disorders of Mitochondrial Energy Metabolism.- Disorders of Pyruvate Metabolism and the Tricarboxylic Acid Cycle.- Disorders of Mitochondrial Fatty Acid Oxidation and Related Metabolic Pathways.- Disorders of Ketogenesis and Ketolysis.- Defects of the Respiratory Chain.- Creatine Deficiency Syndromes.- Disorders of Amino Acid Metabolism and Transport.- Hyperphenylalaninaemia.- Disorders of Tyrosine Metabolism.- Branched-Chain Organic Acidurias/Acidemias.- Disorders of the Urea Cycle and Related Enzymes.- Disorders of Sulfur Amino Acid Metabolism.- Disorders of Ornithine Metabolism.- Cerebral Organic Acid Disorders and Other Disorders of Lysine Catabolism.- Nonketotic Hyperglycinemia (Glycine Encephalopathy).- Disorders of Proline and Serine Metabolism.- Transport Defects of Amino Acids at the Cell Membrane: Cystinuria, Lysinuric Protein Intolerance and Hartnup Disorder.- Vitamin-Responsive Disorders.- Biotin-Responsive Disorders.- Disorders of Cobalamin and Folate Transport and Metabolism.- Neurotransmitter and Small Peptide Disorders.- Disorders of Neurotransmission.- Disorders in the Metabolism of Glutathione and Imidazole Dipeptides.- Trimethylaminuria and Dimethylglycine Dehydrogenase Deficiency.- Disorders ofLipid and Bile Acid Metabolism.- Dyslipidemias.- Disorders of Cholesterol Synthesis.- Disorders of Bile Acid Synthesis.- Disorders of Nucleic Acid and Heme Metabolism.- Disorders of Purine and Pyrimidine Metabolism.- Disorders of Heme Biosynthesis.- Disorders of Metal Transport.- Disorders in the Transport of Copper, Zinc and Magnesium.- Organelle-Related Disorders: Lysosomes, Peroxisomes, and Golgi and Pre-Golgi Systems.- Disorders of Sphingolipid Metabolism.- Mucopolysaccharidoses and Oligosaccharidoses.- Peroxisomal Disorders.- Congenital Disorders of Glycosylation.- Cystinosis.- Primary Hyperoxalurias.

Leseproben

35.1 Inborn Errors of Purine (P. 435)

Metabolism

Inborn errors of purine metabolism comprise errors of: 4 purine nucleotide synthesis: phosphoribosylpyrophosphate (PRPP) synthetase superactivity, adenylosuccinase (ADSL) deficiency, AICA-ribosiduria caused by ATIC deficiency,

4 purine catabolism: the deficiencies of muscle AMP deaminase (AMP-DA, also termed myoadenylate deaminase), adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP) and xanthine oxidase, 4 purine salvage: the deficiencies of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and adenine phosphoribosyltransferase (APRT).

The deficiency of deoxyguanosine kinase causes mitochondrial DNA depletion (7 also Chap. 15). With the exception of muscle AMP-DA deficiency, all these enzyme defects are very rare.

35.1.1 Phosphoribosyl Pyrophosphate Synthetase Superactivity

Clinical Presentation

The disorder is mostly manifested by the appearance, in young adult males, of gouty arthritis and/or uric acid lithiasis, potentially leading to renal insufficiency [1, 2]. Uricemia can be very high, reaching 10–15 mg/dl (0.60– 0.90 mmol/l) [normal adult values: 2.9–5.5 mg/dl (0.17– 0.32 mmol/l)]. The urinary excretion of uric acid is also increased, reaching up to 2400 mg (14 mmol)/24 h, or 2.5 mmol/mmol creatinine [normal adult values: 500– 800 mg (3-4.7 mmol)/24 h, or 02–0.3 mmol/mmol creatinine].

A few patients have been reported in which clinical signs of uric acid overproduction already appeared in infancy and were accompanied by neurologic abnormalities, mainly sensorineural deafness, particularly for high tones, but also hypotonia, locomotor delay, ataxia and autistic features [2].

Metabolic Derangement

The enzyme forms phosphoribosyl pyrophosphate (PRPP) from ribose-5-phosphate and ATP (. Fig. 35.1). PRPP is the first intermediate of the de novo synthesis of purine nucleotides (not shown in full detail in . Fig. 35.1), which leads to the formation of inosine monosphosphate (IMP), from which the other purine compounds are derived.

PRPP synthetase is highly regulated. Various genetic regulatory and catalytic defects [1, 2] lead to superactivity, resulting in increased generation of PRPP. Because PRPP amidotransferase, the rate-limiting enzyme of the de novo pathway, is physiologically not saturated by PRPP, the synthesis of purine nucleotides increases, and hence the production of uric acid.

PRPP synthetase superactivity is one of the few known examples of an hereditary anomaly of an enzyme which enhances its activity. The mechanism of the neurological symptoms is unresolved.

Genetics

The various forms of PRPP synthetase superactivity are inherited as X-linked traits. In the families in which the anomaly is associated with sensorineural deafness, heterozygous females have also been found with gout and/or hearing impairment [2]. Studies of the gene in six families revealed a different single base change in each of them [3].