Abstract:
:To date, inborn errors of neurotransmitters have been defined based on the classic concept of inborn error of metabolism (IEM), and they include defects in synthesis, catabolism, and transport pathways. However, the omics era is bringing insights into new diseases and is leading to an extended definition of IEM including new categories and mechanisms. Neurotransmission takes place at the synapse, the most specialized tight junction in the brain. The concept of "synaptic metabolism" would point to the specific chemical composition and metabolic functions of the synapse. Based on these specialized functions, we aim to provide a tentative overview about the major categories of IEM susceptible to affect neurotransmission. Small molecule defects (biogenic amines and amino acids) and energy defects are amongst the most prevalent diseases reported to disturb the concentration of CSF neurotransmitters. In these IEM, the neurological phenotypes have been largely described. Disorders of complex molecules are not typically considered as diseases affecting neurotransmission. However, most of them have been recently discovered and are involved in intracellular vesiculation, trafficking, processing, and quality control mechanisms. In this large group, neurotransmission is affected in disorders of chaperones and autophagy, disorders of the synaptic vesicle, and diseases affecting pre-synaptic membranes (synthesis and remodeling of complex lipids, defects of glycosylation). Disorders of the vesicle pools, receptor trafficking, and the chronobiology of neurotransmission are potentially emerging new categories. Finally, although not considered as IEM, channelopathies are a large group of diseases disturbing neurotransmitter homeostasis. New CSF biomarkers will probably contribute to improve the diagnosis of these disorders and find new therapeutic targets.
journal_name
J Inherit Metab Disjournal_title
Journal of inherited metabolic diseaseauthors
Tristán-Noguero A,García-Cazorla Àdoi
10.1007/s10545-018-0235-7subject
Has Abstractpub_date
2018-11-01 00:00:00pages
1065-1075issue
6eissn
0141-8955issn
1573-2665pii
10.1007/s10545-018-0235-7journal_volume
41pub_type
杂志文章,评审abstract::GM(2) gangliosidoses are a group of panethnic lysosomal storage diseases in which GM(2) ganglioside accumulates in the lysosome due to a defect in one of three genes, two of which encode the alpha- or beta-subunits of beta- N -acetylhexosaminidase (Hex) A. A small inframe deletion mutation in the catalytic domain of t...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1023/B:BOLI.0000045759.12935.76
更新日期:2004-01-01 00:00:00
abstract::Succinic semialdehyde dehydrogenase (SSAD) is an enzyme involved in the turnover of the neurotransmitter 4-aminobutyrate (GABA). Deficiency of SSAD results in developmental delay, ataxia, seizures and 4-hydroxybutyric aciduria. We have developed a simple fluorimetric assay for the enzyme and applied it to measurement ...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF00711509
更新日期:1993-01-01 00:00:00
abstract::Maple syrup urine disease (MSUD) is an autosomal recessive inherited disease due to a deficiency of any of the subunits, E1 alpha, E1 beta or E2, of the branched-chain alpha-ketoacid dehydrogenase complex (BCKDH). A large Mennonite kindred of MSUD has been studied in Pennsylvania, USA. In the present investigation, ge...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF01799628
更新日期:1992-01-01 00:00:00
abstract::We report molecular analysis of thiamin-responsive pyruvate dehydrogenase complex (PDHC) deficiency in a patient with an X-linked form of Leigh syndrome. PDHC activity in cultured lymphoblastoid cells of this patient and his asymptomatic mother were normal in the presence of a high thiamin pyrophosphate (TPP) concentr...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1023/a:1005305614374
更新日期:1997-08-01 00:00:00
abstract::Lysosomal disease represents a large group of more than 50 clinically recognized conditions resulting from inborn errors of metabolism affecting the organelle known as the lysosome. The lysosome is an integral part of the larger endosomal/lysosomal system, and is closely allied with the ubiquitin-proteosomal and autop...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1007/s10545-008-1040-5
更新日期:2009-04-01 00:00:00
abstract::Unlike normal human cells, cultured fibroblasts from patients with argininosuccinic aciduria cannot synthesize arginine from citrulline because they have a deficiency of argininosuccinic acid lyase (ASL). We have found that V79, a Chinese hamster cell line, cannot grow on citrulline. Although these cells show a normal...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF02312521
更新日期:1980-01-01 00:00:00
abstract::A brief outline of the known biochemical roles of manganese and chromium is given before the problems of determining human trace metal status are discussed. The factors predisposing to trace metal deficiency are reviewed but particular emphasis is placed upon those which alter the bioavailability of essential trace me...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1007/BF01811319
更新日期:1983-01-01 00:00:00
abstract::Every newborn with unexplained neurological deterioration, ketosis, metabolic acidosis or hypoglycaemia should be suspected of having an inherited error of intermediary metabolism. Many of these conditions can be diagnosed clinically with the aid of simple laboratory investigations. Since a substantial number of these...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF01799284
更新日期:1989-01-01 00:00:00
abstract::Recent studies have identified a group of patients with cytochrome oxidase (COX) deficiency presenting in infancy associated with a deficiency of mtDNA in muscle or other affected tissue (Moraes et al 1991). We used a novel approach to compare the level of mitochondrial (mtDNA) compared to nuclear DNA in skeletal musc...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF00711367
更新日期:1995-01-01 00:00:00
abstract::Gonadal function was followed in 26 females and 12 males with galactosaemia due to deficiency of the enzyme galactose-1-phosphate (Gal-1-P) uridyl transferase over a 4 year period. Gonadal function was normal in males, but all females except two had evidence of acquired ovarian failure. Twelve females with ovarian fai...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF01799450
更新日期:1986-01-01 00:00:00
abstract::Aspartylglycosaminuria (AGU) is a lysosomal storage disease caused by deficient activity of glycosylasparaginase (AGA), and characterized by motor and mental retardation. Enzyme replacement therapy (ERT) in adult AGU mice with AGA removes the accumulating substance aspartylglucosamine from and reverses pathology in ma...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-010-9158-7
更新日期:2010-10-01 00:00:00
abstract::Mucopolysaccharidoses are autosomal and recessive lysosomal storage disorders caused by the deficiency of a lysosomal enzyme involved in glycosaminoglycan catabolism. The Sanfilippo type A disease (MPS III A) results from sulfamidase deficiency, which leads to accumulation of heparan sulfate, whereas Sly disease (MPS ...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-009-9029-2
更新日期:2010-02-01 00:00:00
abstract::Insulinaemia and glucagonaemia were measured in two cases of hypercholesterolaemia type II, before and after portacaval shunt. The results show an increase of both hormones although these variations are not concomitant with the decrease in cholesterolaemia. The data still do not explain the mechanism of the decrease. ...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF01801719
更新日期:1980-01-01 00:00:00
abstract::This article documents both the neurological and physical outcomes of the first published set of siblings undergoing transplantation at differing ages for α-mannosidosis. The older brother, the index case, was diagnosed at the age of 3 years and underwent transplantation at 13 years for the treatment of increasing som...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-009-9035-4
更新日期:2010-12-01 00:00:00
abstract::Riboflavin and ubiquinone (Coenzyme Q(10), CoQ(10)) deficiencies are heterogeneous groups of autosomal recessive conditions affecting both children and adults. Riboflavin (vitamin B(2))-derived cofactors are essential for the function of numerous dehydrogenases. Genetic defects of the riboflavin transport have been de...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1007/s10545-011-9434-1
更新日期:2012-07-01 00:00:00
abstract::The different long-chain fatty acid oxidation defects present with similar heterogeneous clinical phenotypes of different severity. Organs mainly affected comprise the heart, liver, and skeletal muscles. All symptoms are reversible with sufficient energy supply. In some long-chain fatty acid oxidation defects, disease...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1007/s10545-010-9090-x
更新日期:2010-10-01 00:00:00
abstract::Cholesterol is known to be a significant constituent of the central nervous system. It also plays an important role in developmental pathways to form the human brain, such as the Sonic Hedgehog pathway. Disturbances in the formation of cholesterol may therefore be expected to cause brain malformations and brain dysfun...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1007/s10545-005-7055-2
更新日期:2005-01-01 00:00:00
abstract::A deficiency in phosphorylase kinase is responsible for several forms of glycogen storage disease which differ in heredity and affected tissues. This is so because phosphorylase kinase consists of four different subunits and has multiple tissue-specific isoforms. To elucidate the molecular basis of phosphorylase kinas...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1007/BF01799500
更新日期:1990-01-01 00:00:00
abstract:OBJECTIVE:There is an urgent need for reliable and universally applicable outcome measures for children with mitochondrial diseases. In this study, we aimed to adapt the currently available Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) to the International Paediatric Mitochondrial Disease Scale (IPMDS) durin...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,多中心研究
doi:10.1007/s10545-016-9948-7
更新日期:2016-09-01 00:00:00
abstract::There are two mechanisms for glucose transport across cell membranes. In the intestine and renal proximal tubule, glucose is transported against a concentration gradient by a secondary active transport mechanism in which glucose is cotransported with sodium ions. In all other cells, glucose transport is mediated by on...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1023/a:1005632012591
更新日期:2000-05-01 00:00:00
abstract::Wilson disease (WD) is an autosomal recessive disorder of copper accumulation leading to liver and/or brain damage. In this paper, we describe the results of a pilot study of screening for WD using ceruloplasmin determinations in dried blood samples. Specimens were collected from children aged 1 to 6 years who were se...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1023/a:1005455401076
更新日期:1999-02-01 00:00:00
abstract::An adult patient with hereditary tyrosinaemia type I who developed renal failure is reported. She received a renal transplant at the age of 23 years. In childhood her kidney disease was dominated by multiple tubular defects with resulting hypophosphataemic rickets. Metabolic acidosis was the most prominent feature in ...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF01804389
更新日期:1991-01-01 00:00:00
abstract::Investigations into the biochemical markers associated with executive function (EF) impairment in children with early and continuously treated phenylketonuria (ECT-PKU) remain largely phenylalanine-only focused, despite experimental data showing that a high phenylalanine:tyrosine (phe:tyr) ratio is more strongly assoc...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,多中心研究
doi:10.1007/s10545-010-9211-6
更新日期:2010-12-01 00:00:00
abstract::Sjögren-Larsson syndrome (SLS) is a rare neurometabolic syndrome caused by deficient fatty aldehyde dehydrogenase. Patients exhibit intellectual disability, spastic paraplegia, and ichthyosis. The accumulation of fatty alcohols and fatty aldehydes has been demonstrated in plasma and skin but never in brain. Brain magn...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1002/jimd.12275
更新日期:2020-11-01 00:00:00
abstract::Acute intermittent porphyria (AIP) caused by mutations in the hydroxymethylbilane synthase gene (HMBS), has been reported in almost all human populations, with varying frequencies. A founder effect for a few specific mutations in geographic regions where prevalence is high (Sweden, The Netherlands, Switzerland) has be...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-010-9228-x
更新日期:2010-12-01 00:00:00
abstract::The progress and extent of myelination can be assessed using magnetic resonance imaging (MRI). Myelination is delayed or diminished in several inherited metabolic abnormalities presenting in early life. Only minimal myelination of the CNS occurs in Pelizaeus-Merzbacher disease. Dysmyelination tends to produce fairly s...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1007/BF00711909
更新日期:1993-01-01 00:00:00
abstract::Isolated sulfite oxidase deficiency (ISOD) is a life-threatening, autosomal recessive disease characterized by severe neurological impairment. As no long-term effective treatment is available, distinction from other treatable diseases, such as molybdenum cofactor deficiency (MoCD) type A, should be made. We reviewed 4...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1007/s10545-017-0089-4
更新日期:2018-01-01 00:00:00
abstract::Aspartylglycosaminuria (AGU, McKusick 20840) is a metabolic disorder affecting the catabolism of glycoproteins. It was first described in 1967, by Jenner and Pollitt, in two mentally retarded English siblings. Subsequently several cases were reported from Finland (Palo and Mattsson, 1970; Autio, 1972; Autio et al., 19...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1007/BF02179139
更新日期:1982-01-01 00:00:00
abstract::Biotinidase deficiency is an autosomal recessive metabolic disorder included in many newborn screening programmes. Prior to the introduction of screening for biotinidase deficiency in Sweden in 2002, the disorder was almost unknown, with only one case diagnosed clinically. Biotinidase activity was measured in dried bl...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-010-9065-y
更新日期:2010-12-01 00:00:00
abstract::In many European countries neonatal screening has been introduced over the last 50 years as an important public health programme. Depending on health care structure, available funds, local politics, input from professional groups, parent groups, and the general public this introduction has led to different approaches ...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-012-9483-0
更新日期:2012-07-01 00:00:00