: John Fernandes, Jean-Marie Saudubray, Walter John Berghe van den Georges
: John Fernandes, Jean-Marie Saudubray, Georges van den Berghe, John H. Walter
: Inborn Metabolic Diseases Diagnosis and Treatment
: Springer-Verlag
: 9783540287858
: 4
: CHF 142.10
:
: Klinische Fächer
: English
: 561
: DRM
: PC/MAC/eReader/Tablet
: PDF

This classical textbook has become indispensable for those in the front line dealing with metabolic disorders. The book is aimed at all those involved with this specialty including pediatricians, biochemists, dieticians, neurologists, internists, geneticists, psychologists, nurses, and social workers. This 4th edition has been thoroughly updated and revised. One new chapter on Neonatal screening by tandem MS/MS has been added and several new groups of disorders have been included. The book's main feature is the strong emphasis on clinical presentation and treatment in acute and chronic situation.
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].
Preface5
Contents7
List of Contributors19
I Diagnosis and Treatment: General Principles24
1 A Clinical Approach to Inherited Metabolic Diseases26
2 Newborn Screening for Inborn Errors of Metabolism72
3 Diagnostic Procedures: Function Tests and Postmortem Protocol81
4 Emergency Treatments93
5 Treatment: Present Status and New Trends103
II Disorders of Carbohydrate Metabolism121
6 The Glycogen Storage Diseases and Related Disorders123
7 Disorders of Galactose Metabolism143
8 Disorders of the Pentose Phosphate Pathway153
Disorders of Fructose Metabolism157
10 Persistent Hyperinsulinemic Hypoglycemia165
11 Disorders of Glucose Transport173
III Disorders of Mitochondrial Energy Metabolism181
12 Disorders of Pyruvate Metabolism and the Tricarboxylic Acid Cycle183
13 Disorders of Mitochondrial Fatty Acid Oxidation and Related Metabolic Pathways197
14 Disorders of Ketogenesis and Ketolysis213
15 Defects of the Respiratory Chain219
16 Creatine Deficiency Syndromes233
IV Disorders of Amino Acid Metabolism and Transport241
17 Hyperphenylalaninaemia243
18 Disorders of Tyrosine Metabolism255
19 Branched- Chain Organic Acidurias/ Acidemias267
20 Disorders of the Urea Cycle and Related Enzymes285
21 Disorders of Sulfur Amino Acid Metabolism295
22 Disorders of Ornithine Metabolism305
23 Cerebral Organic Acid Disorders and Other Disorders of Lysine Catabolism315
24 Nonketotic Hyperglycinemia (Glycine Encephalopathy)329
25 Disorders of Proline and Serine Metabolism337
26 Transport Defects of Amino Acids at the Cell Membrane: Cystinuria, Lysinuric Protein Intolerance and Hartnup Disorder343
V Vitamin-Responsive Disorders352
27 Biotin-Responsive Disorders353
28 Disorders of Cobalamin and Folate Transport and Metabolism363
VI Neurotransmitter and Small Peptide Disorders379
29 Disorders of Neurotransmission381
30 Disorders in the Metabolism of Glutathione and Imidazole Dipeptides395
31 Trimethylaminuria and Dimethyl glycine Dehydrogenase Deficiency403
VII Disorders of Lipid and Bile Acid Metabolism409
32 Dyslipidemias411
33 Disorders of Cholesterol Synthesis433
34 Disorders of Bile Acid Synthesis443
VIII Disorders of Nucleic Acid and Heme Metabolism454
35 Disorders of Purine and Pyrimidine Metabolism455
36 Disorders of Heme Biosynthesis473
37 Disorders in the Transport of Copper, Zinc and Magnesium489
X Organelle-Related Disorders: Lysosomes, Peroxisomes, and Golgi and Pre- Golgi Systems500
38 Disorders of Sphingolipid Metabolism501
39 Mucopolysaccharidoses and Oligosaccharidoses517
40 Peroxisomal Disorders531
41 Congenital Disorders of Glycosylation545
42 Cystinosis553
43 Primary Hyperoxalurias561
Subject Index569