Download or read book Pediatric Neurology Part III written by and published by Newnes. This book was released on 2013-04-24 with total page 731 pages. Available in PDF, EPUB and Kindle. Book excerpt: The child is neither an adult miniature nor an immature human being: at each age, it expresses specific abilities that optimize adaptation to its environment and development of new acquisitions. Diseases in children cover all specialties encountered in adulthood, and neurology involves a particularly large area, ranging from the brain to the striated muscle, the generation and functioning of which require half the genes of the whole genome and a majority of mitochondrial ones. Human being nervous system is sensitive to prenatal aggression, is particularly immature at birth and development may be affected by a whole range of age-dependent disorders distinct from those that occur in adults. Even diseases more often encountered in adulthood than childhood may have specific expression in the developing nervous system. The course of chronic neurological diseases beginning before adolescence remains distinct from that of adult pathology – not only from the cognitive but also motor perspective, right into adulthood, and a whole area is developing for adult neurologists to care for these children with persisting neurological diseases when they become adults. Just as pediatric neurology evolved as an identified specialty as the volume and complexity of data became too much for the general pediatician or the adult neurologist to master, the discipline has now continued to evolve into so many subspecialties, such as epilepsy, neuromuscular disease, stroke, malformations, neonatal neurology, metabolic diseases, etc., that the general pediatric neurologist no longer can reasonably possess in-depth expertise in all areas, particularly in dealing with complex cases. Subspecialty expertise thus is provided to some trainees through fellowship programmes following a general pediatric neurology residency and many of these fellowships include training in research. Since the infectious context, the genetic background and medical practice vary throughout the world, this diversity needs to be represented in a pediatric neurology textbook. Taken together, and although brain malformations (H. Sarnat & P. Curatolo, 2007) and oncology (W. Grisold & R. Soffietti) are covered in detail in other volumes of the same series and therefore only briefly addressed here, these considerations justify the number of volumes, and the number of authors who contributed from all over the world. Experts in the different subspecialties also contributed to design the general framework and contents of the book. Special emphasis is given to the developmental aspect, and normal development is reminded whenever needed – brain, muscle and the immune system. The course of chronic diseases into adulthood and ethical issues specific to the developing nervous system are also addressed. - A volume in the Handbook of Clinical Neurology series, which has an unparalleled reputation as the world's most comprehensive source of information in neurology - International list of contributors including the leading workers in the field - Describes the advances which have occurred in clinical neurology and the neurosciences, their impact on the understanding of neurological disorders and on patient care

Download or read book Pediatric Neurology Part III written by Linda De Meirleir and published by Elsevier Inc. Chapters. This book was released on 2013-04-24 with total page 24 pages. Available in PDF, EPUB and Kindle. Book excerpt: Pyruvate dehydrogenase and pyruvate carboxylase deficiency are the most common disorders in pyruvate metabolism. Diagnosis is made by enzymatic and DNA analysis after basic biochemical tests in plasma, urine, and CSF. Pyruvate dehydrogenase has three main subunits, an additional E3-binding protein and two complex regulatory enzymes. Most frequent are deficiencies in PDH-E1α. There is a spectrum of clinical presentations in E1α deficiency, ranging in boys from severe neonatal lactic acidosis, Leigh encephalopathy, to later onset of neurological disease such as intermittent ataxia or dystonia. Females tend to have a more uniform presentation resembling nonprogressive cerebral palsy. Neuroradiological abnormalities such as corpus callosum agenesis are seen more frequently in girls, basal ganglia and midbrain disturbances in boys. Deficiencies in the other subunits have also been described, but in a smaller number of patients. Pyruvate carboxylase deficiency has three clinical phenotypes. The infantile type is characterized mainly by severe developmental delay, failure to thrive, and seizures. The second type is characterized by neonatal onset of severe lactic acidosis with rigidity and hypokinesia. A third form is rarer with intermittent episodes of lactic acidosis and ketoacidosis. Neuroradiological findings such as cystic periventricular leukomalacia have been described.

Download or read book Pediatric Neurology Part III written by Joerg Klepper and published by Elsevier Inc. Chapters. This book was released on 2013-04-24 with total page 20 pages. Available in PDF, EPUB and Kindle. Book excerpt: Glucide metabolism comprises pathways for transport, intermediate metabolism, utilization, and storage of carbohydrates. Defects affect multiple organs and present as systemic diseases. Neurological symptoms result from hypoglycemia, lactic acidosis, or inadequate storage of complex glucide molecules in neurological tissues. In glycogen storage disorders hypoglycemia indicates hepatic involvement, weakness and muscle cramps muscle involvement. Hypoglycemia is also the leading neurological symptom in disorders of gluconeogenesis. Disorders of galactose and fructose metabolism are rare, detectable by neonatal screening, and manifest following dietary intake of these sugars. Rare defects within the pentose metabolism constitute a new area of inborn metabolic disorders and may present with neurological symptoms. Treatment of these disorders involves the avoidance of fasting, dietary treatment eliminating specific carbohydrates, and enzyme replacement therapy in individual glycogen storage diseases.GLUT1 deficiency syndrome, a specific disorder of glucose transport into brain, results in global developmental delay, early-onset epilepsy, and a complex movement disorder. Treatment with a high-fat, low-carbohydrate ketogenic diet provides ketones as an alternative fuel to the brain and restores brain energy metabolism. Recently paroxysmal exertion-induced dyskinesia and stomatin-deficient cryohydrocytosis have been identified as an allelic disorder to GLUT1 deficiency equally responding to a ketogenic diet.

Download or read book Pediatric Neurology Part III written by Dave Saint-Amour and published by Elsevier Inc. Chapters. This book was released on 2013-04-24 with total page 28 pages. Available in PDF, EPUB and Kindle. Book excerpt: To develop and function optimally, the brain requires a balanced environment of electrolytes, amino acids, neurotransmitters, and metabolic substrates. As a consequence, organ dysfunction has the potential to induce brain disorders and toxic-metabolic encephalopathies, particularly when occurring during early stages of cerebral maturation. Induced toxicity of three different organ systems that are commonly associated with brain complications are discussed. First, thyroid hormone deficiency caused by intrinsic or extrinsic factors (e.g., environmental toxins) may induce severe adverse effects on child neurological development from reversible impairments to permanent mental retardation. Second, inadequate removal of wastes due to chronic renal failure leads to the accumulation of endogenous toxins that are harmful to brain function. In uremic pediatric patients, the brain becomes more vulnerable to exogenous substances such as aluminum, which can induce aluminum encephalopathy. Following surgical procedures, neurological troubles including focal defects and severe epileptic seizures may result from hypertensive encephalopathy combined with toxicity of immunomodulating substances, or from the delayed consequences of cardiovascular defect. Taken together, this illustrates that organ disorders clearly have an impact on child brain function in various ways.

Download or read book Pediatric Neurology Part III written by Andreas Schulze and published by Elsevier Inc. Chapters. This book was released on 2013-04-24 with total page 23 pages. Available in PDF, EPUB and Kindle. Book excerpt: The lack of creatine in the central nervous system causes a severe but treatable neurological disease. Three inherited defects, AGAT, GAMT, and CrT deficiency, compromising synthesis and transport of creatine have been discovered recently. Together these so-called creatine deficiency syndromes (CDS) might represent the most frequent metabolic disorders with a primarily neurological phenotype. Patients with CDS present with global developmental delays, mental retardation, speech impairment especially affecting active language, seizures, extrapyramidal movement disorder, and autism spectrum disorder. The two defects in the creatine synthesis, AGAT and GAMT, are autosomal recessive disorders. They can be diagnosed by analysis of the creatine, guanidinoacetate, and creatinine in body fluids. Treatment is available and, especially when introduced in infancy, has a good outcome. The defect of creatine transport, CrT, is an X-linked condition and perhaps the most frequent reasons for X-linked mental retardation. Diagnosis is made by an increased ratio of creatine to creatinine in urine, but successful treatment still needs to be explored. CDS are under-diagnosed because easy to miss in standard diagnostic workup. Because CDS represent a frequent cause of cognitive and neurological impairment that is treatable they warrant consideration in the workup for genetic mental retardation syndromes, for intractable seizure disorders, and for neurological diseases with a predominant lack of active speech.

Download or read book Pediatric Neurology Part III written by Véronique Abadie and published by Elsevier Inc. Chapters. This book was released on 2013-04-24 with total page 30 pages. Available in PDF, EPUB and Kindle. Book excerpt: Although poorly recognized and studied, congenital sucking, swallowing, and/or feeding disorders are common. They can be the symptoms that reveal a neuromuscular disease, or that complicate a neuromuscular disease. It is essential to know feeding physiology during fetal and infant development in order to understand the variety of its disorders and to direct correctly diagnostic and therapeutic processes. A good semiological analysis will identify the symptoms. Several investigations help to determine the mechanism of the trouble (fiber endoscopy, videofluoroscopy, facial and swallowing electromyography, esophageal manometry, etc.). Other investigations, in addition to clinical assessments, help to identify the cause of the whole picture (peripheral electromyography, brain MRI, genetic or metabolic investigations, etc.). The main causes of sucking, swallowing, and feeding disorders are lesions of the brainstem (malformations of the posterior fossa, neonatal brainstem tumors, agenesis of cranial nerves, clastic lesion of the posterior brain, craniovertebral anomalies, syndromes that involve the rhombencephalic development such as Pierre Robin sequence, CHARGE syndrome, etc.). Suprabulbar lesions, neuromuscular disorders, peripheral esophageal, digestive, and laryngeal anomalies and dysfunctions can also be involved. The main principles of the management of congenital sucking, swallowing, and feeding disorders are the following: cure the cause if possible, facilitate the sucking reflex, preventing deleterious consequences of aspiration, preventing malnutrition, and preventing posttraumatic anorexia. Advice can be given to caregivers and physiotherapists who take charge of these children.

Download or read book Pediatric Neurology Part III written by Stephen G. Kaler and published by Elsevier Inc. Chapters. This book was released on 2013-04-24 with total page 28 pages. Available in PDF, EPUB and Kindle. Book excerpt: Two copper-transporting ATPases are essential for mammalian copper homeostasis: ATP7A, which mediates copper uptake in the gastrointestinal tract and copper delivery to the brain, and ATP7B, which mediates copper excretion by the liver into bile. Mutations in ATP7A may cause three distinct X-linked conditions in infants, children, or adolescents: Menkes disease, occipital horn syndrome (OHS), and a newly identified allelic variant restricted to motor neurons called X-linked distal hereditary motor neuropathy. These three disorders show variable neurological findings and ages of onset. Menkes disease presents in the first several months of life with failure to thrive, developmental delay, and seizures. OHS features more subtle developmental delays, dysautonomia, and connective tissue abnormalities beginning in early childhood. ATP7A-related distal motor neuropathy presents even later, often not until adolescence or early adulthood, and involves a neurological phenotype that resembles Charcot–Marie–Tooth disease, type 2. These disorders may be treatable through copper replacement or ATP7A gene therapy. In contrast, mutations in ATP7B cause a single known phenotype, Wilson disease, an autosomal recessive trait that results from copper overload rather than deficiency. Dysarthria, dystonia, tremor, gait abnormalities, and psychiatric problems may be presenting symptoms, at ages from 10 to 40 years. Excellent treatment options exist for Wilson disease, based on copper chelation. In the past 2 years (2012–2013), three new autosomal recessive copper metabolism conditions have been recognized: 1) Huppke–Brendel syndrome caused by mutations in an acetyl CoA transporter needed for acetylation of one or more copper proteins, 2) CCS deficiency caused by mutations in the copper chaperone to SODI, and 3) MEDNIK syndrome, which revealed that mutations in the σ1A subunit of adaptor protein complex 1 (AP-1) have detrimental effects on trafficking of ATP7A and ATP7B.

Download or read book Pediatric Neurology Part III written by Valayannopoulos Vassili and published by Elsevier Inc. Chapters. This book was released on 2013-04-24 with total page 26 pages. Available in PDF, EPUB and Kindle. Book excerpt: Inborn errors of metabolism may present with acute neurological symptoms at any age. However, especially in neonates and infants, these conditions may be acute and if untreated may lead to permanent cerebral lesions or to death. Knowledge of the main signs and symptoms of these conditions may be lifesaving, especially for conditions that are treatable. From the pathophysiological perspective, errors of metabolism can be divided into disorders causing “intoxication,” disorders impairing energy production, and disorders involving complex molecules. From the clinical perspective, errors of metabolism may present with acute symptoms in the neonatal period and early infancy; late-onset acute and recurrent attacks; chronic and progressive symptoms. Nonspecific readily available biochemical markers may suggest the underlying condition but in most cases the choice of appropriate biochemical and molecular tests is required to establish the diagnosis. Progress in the treatment of inborn errors of metabolism has been slower than progress in diagnostic methods and in understanding of the pathophysiology of these disorders. Nevertheless, outcomes are improving with the use of dialysis and drugs to promote the removal of toxic metabolites and measures to keep catabolism to a minimum. Early intervention is crucial when neurological sequelae could be avoided, which requires constant vigilance and routine measurement of diagnostic biochemical markers in suspected cases.

Download or read book Pediatric Neurology Part III written by Vassili Valayannopoulos and published by Elsevier Inc. Chapters. This book was released on 2013-04-24 with total page 22 pages. Available in PDF, EPUB and Kindle. Book excerpt: Lysosomal storage diseases (LSD) are inborn errors of metabolism secondary to lysosomal enzyme defects and are characterized by a progressive accumulation of nondigested macromolecules provoking cellular dysfunction and clinical manifestations. The diagnosis of these diseases can be confirmed easily in most cases by immuno-enzymatic techniques and molecular biology. Even though these enzymatic deficits result in an accumulation of pathological substrates, the underlying mechanisms responsible for the pathogenesis of the disease are not entirely known. Nevertheless, the distribution of the accumulated material determines the affected organs. More particularly in the central nervous system (CNS), neurons are often involved due to the accumulation of storage material and their incapacity of renewal. LSD can be responsible for mental retardation or for a neurodegenerative course in the central nervous system. The peripheral nervous system and the muscle can also be severely impaired. Hematopoietic stem cell transplantation was the first therapy, demonstrating efficacy especially on the neurological involvement of various LSD. Enzyme replacement therapy is now available for Gaucher disease, Fabry disease, mucopolysaccharidoses type I, type II, and type VI, and Pompe disease. Inhibition of the synthesis of the accumulated substrate by small molecules which also have the capacity to diffuse through the blood–brain barrier is another treatment option. New therapeutic strategies using the properties of molecular chaperones and of read-through molecules for nonsense mutations have been studied in vitro and hopefully will soon find clinical applications while intrathecal enzymes are currently studies in clinical trials for MPSII, MPS IIIA and MLD.

Download or read book Pediatric Neurology Part III written by Atchareeya Wiwatwongwana and published by Elsevier Inc. Chapters. This book was released on 2013-04-24 with total page 27 pages. Available in PDF, EPUB and Kindle. Book excerpt: We review the supranuclear control centers and pathways leading to individual cranial nerve nuclei in the brainstem. We discuss horizontal and vertical gaze and their abnormalities, and review the cranial nerves which subserve eye movements, III, IV, VI, including their clinical testing. We highlight the sites at which these nerves are clinically affected, which often result in characteristic associated features with neurological localizing value. Differential diagnoses of cranial nerve palsies including Duane and Möbius syndromes are also described. Lastly, we discuss the nature of childhood neuromuscular junction disorders such as myasthenia gravis, as well as disorders of the muscle itself (chronic progressive external ophthalmoplegia (CPEO), thyroid orbitopathy).

Download or read book Pediatric Neurology Part III written by Georg F. Hoffmann and published by Elsevier Inc. Chapters. This book was released on 2013-04-24 with total page 49 pages. Available in PDF, EPUB and Kindle. Book excerpt: Symptoms in patients with defects in amino acid catabolism and the urea cycle usually develop because of intoxication of accumulating metabolites. The cumulative prevalence of these disorders is considerable (at least>1:2000 newborns). Timely and correct intervention during the initial presentation and during later episodes is most important. Evaluation of metabolic parameters should be performed on an emergency basis in every patient with symptoms of unexplained metabolic crisis, intoxication, and/or unexplained encephalopathy. A substantial number of patients develop acute encephalopathy or chronic and fluctuating progressive neurological disease. The so-called cerebral organic acid disorders present with (progressive) neurological symptoms: ataxia, myoclonus, extrapyramidal symptoms, and “metabolic stroke.” Important diagnostic clues, such as white matter abnormalities, cortical or cerebellar atrophy, and injury of the basal ganglia can be derived from cranial magnetic resonance imaging (MRI). Long-term neurological disease is common, particularly in untreated patients, and the manifestations are varied, the most frequent being (1) mental defect, (2) epilepsy, and (3) movement disorders. Successful treatment strategies are becoming increasingly available. They mostly require an experienced interdisciplinary team including a neuropediatrician and/or later on a neurologist.

Download or read book Pediatric Neurology Part III written by Nardo Nardocci and published by Elsevier Inc. Chapters. This book was released on 2013-04-24 with total page 21 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Neuroaxonal Dystrophies (NADs) are a group of clinically and genetically heterogeneous neurodegenerative conditions. These disorders show the unique pathological feature of neuroaxonal dystrophy (NAD): axonal swelling (spheroids) localized throughout the central nervous and peripheral nervous systems. NADs are also morphologically characterized by iron accumulation in the basal ganglia; and are now included in the group of diseases called neurodegeneration with brain iron accumulation (NBIA). NADs comprise two main diseases: pantothenate-kinase associated neurodegeneration (PKAN) and infantile neuroaxonal dystrophy (INAD). PKAN in caused by mutation in the PANK-2 gene. In classic PKAN onset of disease is in the first decade and patients show dystonia, rigidity and dysarthria; course is progressive leading to loss of autonomous gait within 15 years. In atypical PKAN age at onset is later and progression slower. Psychiatric symptoms, obsessive-compulsive disorder, and tourettism may be prominent. In classic INAD patients present with psychomotor regression between 6 months-3 years, followed by neurological deterioration leading to tetraparesis, optic atrophy, and dementia. Atypical NAD refers to all patients who differ from the classical phenotype in term of age at onset and disease progression. Mutations in PLA2G6 gene are found both in classic and atypical INAD patients.

Download or read book Pediatric Neurology Part III written by Jean-Marie Girard and published by Elsevier Inc. Chapters. This book was released on 2013-04-24 with total page 23 pages. Available in PDF, EPUB and Kindle. Book excerpt: The progressive myoclonus epilepsies (PMEs) consist of a group of diseases with myoclonic seizures and progressive neurodegeneration, with onset in childhood and/or adolescence. Lafora disease is a neuronal glycogenosis in which normal glycogen is transformed into starch-like polyglucosans that accumulate in the neuronal somatodendritic compartment. It is caused by defects of two genes of yet unknown function, one encoding a glycogen phosphatase (laforin) and the other an ubiquitin E3 ligase (malin). Early cognitive deterioration, visual seizures affecting over half, and slowing down of EEG basic activity are three major diagnostic clues. Unverricht–Lundborg disease is presently thought to be due to damage to neurons by lysosomal cathepsins and reactive oxygen species due to absence of cystatin B, a small protein that inactivates cathepsins and, by ways yet unknown, quenches damaging redox compounds. Preserved cognition and background EEG activity, action myoclonus early morning and vertex spikes in REM sleep are the diagnostic clues. Sialidosis, with cherry-red spot, neuronopathic Gaucher disease, with paralysis of verticality, and ataxia-PME, with ataxia at onset in the middle of the first decade, are also lysosomal diseases. How the lysosomal defect culminates in myoclonus and epilepsy in these conditions remains unknown.

Download or read book Pediatric Neurology Part III written by Matthias R. Baumgartner and published by Elsevier Inc. Chapters. This book was released on 2013-04-24 with total page 34 pages. Available in PDF, EPUB and Kindle. Book excerpt: The catalytic properties of many enzymes depend on the participation of vitamins as obligatory cofactors. Vitamin B12 (cobalamin) and folic acid (folate) deficiencies in infants and children classically present with megaloblastic anemia and are often accompanied by neurological signs. A number of rare inborn errors of cobalamin and folate absorption, transport, cellular uptake, and intracellular metabolism have been delineated and identification of disease-causing mutations has improved our ability to diagnose and treat many of these conditions. Two inherited defects in biotin metabolism are known, holocarboxylase synthetase and biotinidase deficiency. Both lead to multiple carboxylase deficiency manifesting with metabolic acidosis, neurological abnormalities, and skin rash. Thiamine-responsive megaloblastic anemia is characterized by megaloblastic anemia, non-type I diabetes, and sensorineural deafness that responds to pharmacological doses of thiamine (vitamin B1). Individuals affected with inherited vitamin E deficiencies including ataxia with isolated vitamin E deficiency and abetalipoproteinemia present with a spinocerebellar syndrome similar to patients with Friedreich's ataxia. If started early, treatment of these defects by oral or parenteral administration of the relevant vitamin often results in correction of the metabolic defect and reversal of the signs of disease, stressing the importance of early and correct diagnosis in these treatable conditions.

Download or read book Pediatric Neurology Part III written by Marie T. Vanier and published by Elsevier Inc. Chapters. This book was released on 2013-04-24 with total page 17 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Niemann–Pick disease group is now divided into two distinct entities: (1) acid sphingomyelinase-deficient Niemann–Pick disease (ASM-deficient NPD) resulting from mutations in the SMPD1 gene and encompassing type A and type B as well as intermediate forms; (2) Niemann–Pick disease type C (NP-C) including also type D, resulting from mutations in either the NPC1 or the NPC2 gene. Both Niemann–Pick diseases have an autosomal recessive inheritance and are lysosomal lipid storage disorders, with visceral (type B) or neurovisceral manifestations. The clinical knowledge is updated taking into account recent surveys in large cohort of patients, particularly for type B and type C. The diagnosis of NP-C is often delayed due to the wide spectrum of clinical phenotypes. Systemic manifestations, if present, always precede onset of neurological manifestations. Most common neurological signs are vertical supranuclear gaze palsy, cerebellar ataxia, dysarthria, dysphagia, and progressive dementia. Cataplexy, seizures, and dystonia are other common features of NP-C. For both ASM-deficient NPD and NP-C, strategies for laboratory diagnosis of patients and prenatal diagnosis are discussed. Recent progress towards enzyme replacement therapy in type B patients and management of the neurological disease in type C patients are finally highlighted.

Download or read book Pediatric Neurology Part III written by Cyril Mignot and published by Elsevier Inc. Chapters. This book was released on 2013-04-24 with total page 24 pages. Available in PDF, EPUB and Kindle. Book excerpt: Gaucher disease is an autosomal recessive condition due to glucocerebrosidase deficiency responsible for the lysosomal accumulation of glucosylceramide, a complex lipid derived from cell membranes, mainly in macrophages. It is due to mutations mostly in the GBA gene, although saposine C deficiency is due to mutations in the PSAP gene. It encompasses an extremely heterogeneous spectrum of clinical involvement from the fetus to adulthood. Splenomegaly, blood cytopenia, and bone involvement are the main manifestations of Gaucher disease, but nervous system degeneration is observed in about 5–10% of patients. The accumulation in neurons of glucosylceramide and its derivative, psychosine, are thought to underlie neuronal dysfunction and death, although Gaucher cells that mostly accumulate such substances are mainly macrophages. Enzyme replacement therapy dramatically improves the outcome of patients because of its extreme efficacy in the treatment of the systemic involvement. However, it has only limited effects on most neurological signs.

Download or read book Pediatric Neurology Part III written by H.A. Jinnah and published by Elsevier Inc. Chapters. This book was released on 2013-04-24 with total page 29 pages. Available in PDF, EPUB and Kindle. Book excerpt: The purines are a group of molecules used by all cells for many vital biochemical processes including energy-requiring enzymatic reactions, cofactor-requiring reactions, synthesis of DNA or RNA, signaling pathways within and between cells, and other processes. Defects in some of the enzymes of purine metabolism are known to be associated with specific clinical disorders, and neurological problems may be a presenting sign or the predominant clinical problem for several of them. This chapter describes three disorders for which the clinical features and metabolic basis are well characterized. Deficiency of adenylosuccinate-lyase (ADSL) causes psychomotor retardation, epilepsy, and autistic features. Lesch–Nyhan disease is caused by deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) and is characterized by hyperuricemia, motor and cognitive disability, and self-injurious behavior. Deficiency of myoadenylate deaminase (mAMPD) is associated with myopathic features. In addition to these disorders, several other disorders are briefly summarized. These include defects of phosphoribosylpyrophosphate synthase, adenosine deaminase (ADA), purine nucleoside phosphorylase (PND), deoxyguanosine kinase (dGK), or IMP dehydrogenase (IMPDH). Each of these disorders provides an unusual window on the unique importance of purine metabolism for function of different parts of the nervous system.