Journal of pediatric biochemistry最新文献

{"title":"The Oxidative Stress Effects in Neonatal Diseases from Molecular Mechanisms to Therapeutic Potential","authors":"S. Perrone, G. Buonocore","doi":"10.1055/s-0036-1593758","DOIUrl":"https://doi.org/10.1055/s-0036-1593758","url":null,"abstract":"Free radicals (FRs) are continuously produced during aerobic metabolism and are characterized by high reactivity. They participate in many important physiological processes, but if produced in high concentrations, they lead to oxidative stress (OS) development and disturb pro-oxidative/antioxidative balancetowardtheoxidationof lipids,proteins,carbohydrates, or nucleic acids. 1 Each of these reactions may have deleterious consequences and differential effects on the distinct cell populations of the body, with certain speci fi c cell types being particularly vulnerable in perinatal period. 2 Pathologies resulting from oxidative damage are grouped together and categorized as “ free radical disease in the neonate ” (FRD). Such pathologies include retinopathy of prematurity (which in severe cases may lead to blindness), bronchopulmonary dysplasia (a particularly debilitating pulmonary lesion in the preterm infant), periventricular leukomalacia (an important cause of severe neurodisability in premature infants)","PeriodicalId":89425,"journal":{"name":"Journal of pediatric biochemistry","volume":"06 1","pages":"71 - 72"},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0036-1593758","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"58178110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective Effects of Melatonin on Free Radical-Induced Oxidative Stress","authors":"E. Belvisi, S. Carloni, M. Tei, M. Alagna, A. Santacroce, M. Riccitelli, F. Bazzini, M. Longini, G. Buonocore, S. Perrone","doi":"10.1055/s-0036-1593813","DOIUrl":"https://doi.org/10.1055/s-0036-1593813","url":null,"abstract":"Abstract Melatonin is both a potent free radical (FR) scavenger and a broad-spectrum antioxidant. It seems to give useful effects in newborn disorders as has been shown for adults. The unbalance between prooxidant and antioxidant factors leads to oxidative stress (OS) and damage to biomolecules. OS is involved in the pathogenesis of many chronic diseases in adulthood, such as atherosclerosis, cancer, diabetes, rheumatoid arthritis, stroke and postischemic perfusion injury, myocardial infarction and cardiovascular diseases, chronic inflammation, septic shock, aging, and other degenerative diseases Nevertheless, there is growing evidence that OS is involved in the pathogenesis of many fetal and newborn diseases. The unbalance between a low-efficient antioxidant system and an overproduction of FR, especially in preterm babies, leads to the so-called FR-related disease of newborns, characterized by several cellular, tissue, and organ damage (kidney, retina, lung, bowel, and brain injury). Among antioxidants, melatonin (MLT) shows high antioxidant and anti-inflammatory properties: it is able to scavenge dangerous FR; it induces the production of antioxidant enzymes; it has no prooxidant effects; and it is safe. During the last decade, MLT has started to be considered as an attractive option to minimize as much as possible the sequelae from OS damage: in damaged lung tissue, MLT attenuates the hyperoxia-induced depletion of antioxidant enzyme activities and reduces proinflammatory cytokines; in animal model affected with necrotizing enterocolitis (NEC), MLT reduces tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β), lipid peroxidation products, reactive oxygen species/reactive nitrogen species (ROS/RNS), and it reverses lipopolysaccharide-induced motility disturbances; in developing retina, MLT prevents retinal ganglion cell death through its antioxidant and anti-inflammatory properties. In particular, MLT appears as a very interesting drug to reduce the neurological sequelae from hypoxic-ischemic brain injury. Because of its lipophilic properties, MLT easily crosses most biological cell membranes, including the placenta and the blood–brain barrier and may prevent neonatal brain injury in early stage of life. The neuroprotective role of MLT calls for further investigation in the newborn infants.","PeriodicalId":89425,"journal":{"name":"Journal of pediatric biochemistry","volume":"06 1","pages":"103 - 109"},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0036-1593813","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"58177957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Dysfunction and Oxidative Stress in Pediatric Diseases","authors":"F. Lotti, S. Perrone, Ursula Geronzi, E. Guidoni, F. Carra, E. Belvisi, F. Bazzini, G. Buonocore, S. Grosso","doi":"10.1055/s-0036-1593756","DOIUrl":"https://doi.org/10.1055/s-0036-1593756","url":null,"abstract":"Abstract Oxidative stress is a distinctive sign in a long series of human diseases, including metabolic, neurologic, and cancer disorders. Several studies demonstrated that the toxic effects resulting from a redox imbalance take place even during infant age. Recent literature focused in particular on the role exerted by unpaired mitochondrial function in the pathogenesis of these diseases. Oxidative damage and mitochondrial dysfunction are cofactors in the pathogenesis of diabetes, as well as major contributors to its associated complications, primarily represented by cardiovascular disease. In epilepsy, mitochondrial failure is thought to be one of the possible mechanisms for seizure generation through a dysregulation in calcium homeostasis; moreover, the prolonged seizure-related neuronal excitation is able to trigger mitochondrial damage, proving the existence of interdependency between epileptic activity and mitochondrial dysfunction. Oxidative stress plays a pivotal role in carcinogenesis, and its intervention has been demonstrated in the pathogenesis of cancer-prone genetic diseases. The identification of specific molecular targets linked to altered mitochondrial function allows to select more rational and appropriate supportive treatments using antioxidants and mitochondrial nutrients as potential new therapeutic approaches.","PeriodicalId":89425,"journal":{"name":"Journal of pediatric biochemistry","volume":"06 1","pages":"79 - 87"},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0036-1593756","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"58178053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Free Radical Diseases of Newborn","authors":"S. Perrone, M. Tataranno, S. Negro, A. Santacroce, N. D. Virgilio, E. Belvisi, F. Proietti, F. Bazzini, G. Buonocore","doi":"10.1055/s-0036-1593757","DOIUrl":"https://doi.org/10.1055/s-0036-1593757","url":null,"abstract":"Abstract Free radicals (FRs) are unstable, short lived, and highly reactive molecules that are continuously generated by endogenous and exogenous mechanisms. The burden of FR generation is counteracted by the intracellular antioxidant systems, and the maintenance of oxidant/antioxidant balance is critical to normal cellular functions. The dangerous effects of FRs are linked to their property of being very unstable molecules and their ability to react with polyunsaturated fatty acids of cell membranes, proteins, polysaccharides, nucleic acids, causing functional alterations within the cell. In neonatal period, hypoxia, ischemia, ischemia-reperfusion, hyperoxia, inflammation, mitochondrial impairment, presence of nonprotein bound iron are responsible of excessive FRs production. Moreover, a less efficient antioxidant system is not able to counteract the harmful effects of FRs leading to FR-related cellular, tissue, and organ damages. In preterm babies, the severity of mechanisms responsible of FRs production, the stage at which the oxidative insult occurs, the degree of maturity of the organs have differential effects on the distinct cell populations of the body, with certain specific cell types being particularly vulnerable in perinatal period. We propose the hypothesis that oxidative stress (OS) is the common pathogenic factor involved in the onset and develop of intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, bronchopulmonary dysplasia, and necrotizing enterocolitis. This suggests that developing effective antioxidant strategies for preterm infants requires a detailed understanding of oxidative stress reactions and cell responses in perinatal period.","PeriodicalId":89425,"journal":{"name":"Journal of pediatric biochemistry","volume":"06 1","pages":"73 - 78"},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0036-1593757","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"58178100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurological Involvement in Inherited Metabolic Diseases: An Overview","authors":"Ferdinando Ceravolo, S. Sestito, F. Falvo, V. Salpietro, A. Polizzi, M. Ruggieri, Mercuri Francesco Bruno, D. Concolino","doi":"10.1055/s-0036-1582235","DOIUrl":"https://doi.org/10.1055/s-0036-1582235","url":null,"abstract":"Abstract Neurological involvement is a typical feature of several inherited metabolic diseases. The onset of signs and/or symptoms may appear as early as the first days of life or after an interval of normal or near-normal growth and development. Metabolic decomposition usually presents with a severe clinical phenotype, which include poor feeding, vomiting, lethargy, seizures, and loss of consciousness. This spectrum of manifestations is often fatal; however, severe neurological sequelae and/or regression of neurodevelopmental milestones can be the prominent signs in those who survive. Overall, treatable inborn errors of metabolism can be divided in three groups, namely: (Group 1) inborn errors of intermediary metabolism giving rise to acute or chronic intoxication; (Group 2) inborn errors of intermediary metabolism affect in genergetic processes; and (Group 3) inborn errors involving cellular organelles, including lysosomal, peroxisomal, glycosylation, and cholesterol synthesis defects. The spectrum of neurological manifestations includes developmental delay, seizures and epilepsy, pyramidal and extrapyramidal signs, movement disorders, vision and hearing impairment, peripheral neuropathy, and psychiatric abnormalities. The main anatomical/imaging patterns reflects selective vulnerability of nervous system substance and include atrophy, (predominantly) symmetrical abnormalities, and dysmyelination, As several patients with neurometabolic diseases responds favorably to therapeutic trials, early detection and early intervention is of utmost importance to prevent catabolic-related damage and to revert to normal or near-normal parameters neurodevelopmental milestones.","PeriodicalId":89425,"journal":{"name":"Journal of pediatric biochemistry","volume":"25 1","pages":"003 - 010"},"PeriodicalIF":0.0,"publicationDate":"2016-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0036-1582235","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"58141485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanded Newborn Screening: A Chess Board Motif in Public Health","authors":"A. Polizzi, P. Carbone, D. Taruscio","doi":"10.1055/s-0036-1582225","DOIUrl":"https://doi.org/10.1055/s-0036-1582225","url":null,"abstract":"Abstract Inborn errors of metabolism (IEM) include a large number of genetic disorders caused by lack of functional proteins that result in a blockage of the corresponding metabolic pathway essential for cellular life. IEM are rare or even very rare conditions, whereas with a collective incidence comprised from 1:800 to 1:2,500 live births. Approximately half of all IEM can be treated biochemically, although the success of such treatment is variable. IEM (especially in the neonatal age) may have a rapid evolution to severe and irreversible neurological and mental deficits, coma, and death. Early diagnosis, allowing presymptomatic treatment, can ameliorate prognosis, prevent severe permanent sequelae, and in certain cases avoid death. To ensure accurate diagnosis, effective treatment, and appropriate follow-up, preventive medicine have implemented for IEM screening programs as a powerful tool of secondary prevention. In this respect, expanded newborn screening programs have increased dramatically in the past decade although the number of diseases included in the screening panel varies from state to state. As a consequence, some nations screen for only one or two IEM, some others for several more (up to a few dozen IEM) leading to an inequality of preventive measures in such as delicate fields. Criteria to support and include screening for a specific condition in each country stand from legislation, financial costs prevalence of the disease in that country, availability of treatments, and dedicated funding sources. Currently, lack of sound and complete evidence, as well as different interpretations of the best evidence available, could also be among the factors contributing to the different screening panels across diverse countries worldwide. Within this view, the recommendable approach to assess current newborn screening programs should be based on the methodologies of health technology assessment, taking into account health economics evidence and ethics applied to well-being policies.","PeriodicalId":89425,"journal":{"name":"Journal of pediatric biochemistry","volume":"06 1","pages":"066 - 070"},"PeriodicalIF":0.0,"publicationDate":"2016-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0036-1582225","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"58141473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Childhood Neurometabolic Disorders","authors":"D. Concolino","doi":"10.1055/s-0036-1582236","DOIUrl":"https://doi.org/10.1055/s-0036-1582236","url":null,"abstract":"Although individual inborn errors of metabolism are relatively rare conditions, as a group they reach a cumulative incidence varying between 1 in 1,500 and 1 in 5,000 live births. From the initial discoveries in this field, summarized by Garrod in his book Inborn Errors of Metabolism some 80 years ago,1 approximately 1,000 inborn errors of metabolism are estimated to have been identified to date.2 Considerable efforts were made through years to understand the pathophysiological aspects of metabolic diseases: from biochemical progress in the 1960s when the identification of metabolic products in urine, blood, or neural tissues became possible and allowed the identification of the enzymes responsible for metabolic alterations, to the genetic approach in the 1980s when the identification of genetic mutations permitted to uncover the genetic defects responsible for neurological diseases, to today’s proteomics and metabolomics techniques.3 Inherited disorders of metabolism encompass a narrow spectrum of conditions that have been biochemically defined. Broad categories include disorders of carbohydrate metabolism, disorders of amino acid metabolism, organic acidemias, lysosomal storage diseases, disorders of fatty acid metabolism, and mitochondrial disorders. Most of these conditions are associated with neurologic sequelae.4 The aim of this special issue entitled “Childhood neurometabolic disorders” is to analyze themost recent studies that have been conducted on the most frequent inherited metabolic diseases with neurological involvement. First, we present overview of the metabolic disorders devoting a particular attention to the involvement of the nervous system, especially in those neurological alterations that may exhibit an acute neonatal onset. At this age, neurological alterations such as coma, hypotonia, and seizures could be secondary not only to metabolic imbalances directly involving the central nervous system (CNS) but also to critical clinical conditions caused by metabolic intoxication and organ failures. Thereafter, we analyze hyperphenylalaninemia (HPA), one of the metabolic diseases with a natural history that was changed thanks to the introduction of neonatal screening programs. Early recognition of elevated blood concentrations of phenylalanine (Phe) permitted to start therapy early in the neonatal period and to prevent the development of neurological impairment in affected babies. The first used therapeutic approach was the administration of a diet poor in Phe that resulted in effective maintenance of low blood Phe concentrations. This approach continues to be used to treat HPA patients, although it is associated with compliance problems because of its dietary restriction. In addition to diet, an increasing number of different therapies are now available or are under study. One of the most important alternatives is the treatment of these patients with a BH4 analogue, which is used in classical HPA, in those patients whose enzymatic ","PeriodicalId":89425,"journal":{"name":"Journal of pediatric biochemistry","volume":"06 1","pages":"001 - 002"},"PeriodicalIF":0.0,"publicationDate":"2016-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0036-1582236","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"58141511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurological Involvement in Tetrahydrobiopterin Deficiency","authors":"I. Mascaro, Ferdinando Ceravolo, S. Ferraro, D. Procópio, F. Falvo, M. Grisolia, Giuseppina Leone, V. Salpietro, A. Polizzi, M. Ruggieri, D. Concolino","doi":"10.1055/s-0036-1582250","DOIUrl":"https://doi.org/10.1055/s-0036-1582250","url":null,"abstract":"Abstract Tetrahydrobiopterin (BH4) is a natural and essential cofactor for the enzymatic hydroxylation of phenylalanine (Phe) and tyrosine (Tyr), and for two tryptophan hydroxylases, three nitric oxide synthases, and glyceryl-ether monooxygenase. Five separate genetic conditions affecting BH4 synthesis or recycling have been identified so far, including deficiency in (1) 6-pyruvoyltetrahydropterin synthase; (2) dihydropteridine reductase; (3) GTP cyclohydrolase I; (4) sepiapterin reductase; and (5) pterin-4α-carbinolamine dehydratase. These disorders cause hyperphenylalaninemia and impaired synthesis of serotonin and dopamine since tyrosine hydroxylase and neuronal tryptophan hydroxylase require BH4 and serotonin/dopamine products (5-hydroxytryptophan and L-dopa). All these five genetic conditions can be identified by newborn screening procedures due to elevated blood levels of Phe (with the sole exception of sepiapterin reductase deficiency). BH4 loading tests and measurement of neurotransmitter metabolites, pterins, and folates in cerebrospinal fluid can add further important information on disease severity. Untreated patients develop a complex neurological phenotype, which includes Parkinson-like features, brain degeneration, and early death. The gold standard treatment of severe disorders of BH4 metabolism is based on replacement therapy with BH4, 5-hydroxytryptophan, L-dopa, and carbidopa, with the addition, in certain cases, of folinic acid supplements and pramipexole. Dopamine agonists can improve L-dopa therapy, making treatment easier, relieving symptoms, stabilizing clinical course, and possibly ameliorating long-term outcomes. The outcome of patients with disorders of biopterin synthesis can be favorable, with either normal or near-normal cognition, and with some residual neurological symptoms usually manifesting diurnal variation, that is, worst when patients become tired or when the dosage or interval for medications is inadequate.","PeriodicalId":89425,"journal":{"name":"Journal of pediatric biochemistry","volume":"06 1","pages":"019 - 024"},"PeriodicalIF":0.0,"publicationDate":"2016-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0036-1582250","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"58141537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Different Forms of Mucopolysaccharidosis with Neurological Involvement: A Case-Based Review","authors":"F. Falvo, S. Sestito, A. Nicoletti, M. Grisolia, I. Mascaro, E. Pascale, V. Salpietro, A. Polizzi, M. Ruggieri, D. Concolino","doi":"10.1055/s-0036-1582252","DOIUrl":"https://doi.org/10.1055/s-0036-1582252","url":null,"abstract":"Abstract The mucopolysaccharidoses (MPSs) are a group of rare lysosomal storage disorders caused by deficiency of enzymes catalyzing the stepwise degradation of glycosaminoglycans dermatan sulfate, heparan sulfate, keratan sulfate, chondroitin sulfate, and hyaluronic acid. There are seven groups of MPS, which are MPS-I (MPS-I-H or Hurler syndrome; MPS-I-S or Scheie syndrome; and MPS-I-HS or Hurler–Scheie syndrome), MPS-II (Hunter syndrome), MPS-III (Sanfilippo syndrome types A to D), MPS-IV (Morquio syndrome types A and B), MPS-VI (Maroteaux–Lamy syndrome), MPS-VII (Sly syndrome), and MPS-IX (Natowicz syndrome). All are inherited as autosomal recessive diseases, with the exception of Hunter syndrome, which follows an X-linked recessive inheritance pattern. The MPSs affect multiple organ systems (including bone, heart, and visceral organs), leading to organ failure. Involvement of central nervous system occurs only in the forms with heparan sulfate accumulation, that is, MPS-I, MPS-II, MPS-III, and MPS-VII. Therapy is available for MPS-I, MPS-II, MPS-IV, and MPS-VI. This review provides a case-based overview of the different forms of MPS with neurological involvement.","PeriodicalId":89425,"journal":{"name":"Journal of pediatric biochemistry","volume":"06 1","pages":"046 - 052"},"PeriodicalIF":0.0,"publicationDate":"2016-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0036-1582252","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"58141563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurological Findings in Anderson-Fabry Disease","authors":"A. Nicoletti, S. Sestito, F. Falvo, I. Mascaro, M. Moricca, V. Salpietro, A. Polizzi, M. Ruggieri, Mercuri Francesco Bruno, D. Concolino","doi":"10.1055/s-0036-1582223","DOIUrl":"https://doi.org/10.1055/s-0036-1582223","url":null,"abstract":"Abstract Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder caused by mutations in the α-galactosidase A gene on chromosome Xq22, resulting in α-galactosidase A enzyme deficiency. It is characterized by progressive accumulation of lipids (e.g., globotriaosylceramide) in the lysosomes of a variety of cell types, including neural cells. Neurological manifestations, other than cerebrovascular accidents, include small fiber neuropathy and dysautonomic disorders. Small fiber peripheral neuropathy often is clinically manifested at young ages. Peripheral pain can be chronic and/or can occur as provoked attacks of excruciating pain. Manifestations of dysfunction of small autonomic fibers may include impaired sweating, gastrointestinal dysmotility, and abnormal pain perception. Patients with AFD often remain undiagnosed until the emergence of a more typical clinical manifestation, characterized by chronic renal and cardiac failure. Early clinical benefits of enzyme replacement therapy include reduction of neuropathic pain, and adequate management of residual pain to a tolerable and functional level, which can substantially improve the quality of these patients. Thus, it is important that physicians consider AFD in the differential diagnosis of neurological manifestations to provide an appropriate diagnostic and therapeutic workup.","PeriodicalId":89425,"journal":{"name":"Journal of pediatric biochemistry","volume":"06 1","pages":"053 - 059"},"PeriodicalIF":0.0,"publicationDate":"2016-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0036-1582223","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"58141398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}