Figure 1. Main neurological presentations, pathophysiological categories, and neurodevelopmental to neurodegenerative features. Main clinical presentations are presented depending on the severity degree, from antenatal malformations to isolated symptoms. It is not rare that the same disease could have different types of presentation. Severe global encephalopathies include genetic defects that lead to early disruption of fundamental biological processes that are required for a proper brain development and affect motor, cognitive and behavioural aspects. Synaptopathies correspond to diseases impairing synaptic communication and often have epilepsy, intellectual disability, behavioural abnormalities (including autism) and movement disorders in any combination. Synaptic diseases produce connectivity impairments (abnormal brain circuitries' organization). Complex motor presentations correspond to diseases leading to abnormal motor symptoms; these are related to brain structures and circuits that regulate voluntary and passive movements, strength, and muscle tone. In pediatrics' IEMs it is not rare to detect combinations of different motor signs (dyskinetic movements, pyramidal signs, hypotonia, ataxia...). Some additional explanations: COG6 plays a major role in Golgi trafficking and positioning of glycosylation enzymes. HCFC1: gene responsible for X-linked cobalamin deficiency. PHARC: Acronym for a neuropathy syndrome due to a phospholipid remodeling defect that mimics Refsum disease. PIGA is one of the 7 proteins required for the 1st step of the GPI synthesis. SERAC1: protein with a lipase domain involved in the remodeling of phosphatidylglycerol, bis monoacyl glycerol phosphate and cardiolipin. SNAP29: encodes for a SNARE protein involved in vesicle fusion. SNX14: gene mutations responsible for childhood ARCA syndrome (Autosomic Recessive Cerebellar Ataxia). VPS15: is implicated in endosomal-lysosomal trafficking and autophagy. WDR45: interacts with autophagy proteins Atg2 and Atg9 to regulate autophagosome formation and elongation. Ast: aspartate transporter; Asp: asparagine synthetase; ADSL: adenylosuccinate lyase deficiency: BCAA: branched chain amino acid; BetaM: β mannosidosis; CAD: enzymatic complex responsible for the first 3 steps of the de novo pyrimidine synthesis; Cbl: cobalamin; Cholest: cholesterol; CholK: choline kinase; COG6: conserved oligomeric Golgi complex; CDG: Congenital disorder of glycosylation; CERS: ceramide synthetase; DARS2: mt aspartyl-tRNA synthetases; EARS2: mt glutamyl-tRNA synthetases; ELOVL4: fatty acid elongase 4; FAt: fatty acid transporter; FAs: fatty acid synthetase; FADH: fatty alcohol deshydrogenase; FAHN: fatty acid hydroxylase associated neurodegeneration; FARS 2: mt phenylalanine-tRNA synthetases; GABA:y aminobutyric acid; Glu: glutamine synthetase; GLUT1: glucose transporter; GluR: glutamate receptor; GlyR: glycine receptor; GM: ganglioside; HCFC1: host cell factor C1; HHH: hyperammonemia, hyperornithinemia, homocitrullinemia syndrome; MARS2: mt methionyl-tRNA synthetases. MTHFR: methyltetrahydrofolate reductase; MD: movement disorders; ML: mucolipidosis; MLD: metachromatic leucodystrophy; MPS III: mucopolysaccharidosis type III (sanfilippo disease); NBIA: neurodegeneration with brain iron accumulation; NCL: neuronal ceroid lipofuschinosis; NPSY: neuropsychiatric symptoms; OA: organic aciduriasO-gly: O-glycosylation; PC: pyruvate carboxylase; PDH: pyruvate deshydrogenase; perox: peroxysome biogenesis defects; PHARC: polyneuropathy, hearing loss, ataxia, retinitis pigmentosa and cataracts; PIGA: phosphatidylinositol glucosaminyltransferase; P13K/AKT: phosphatidyl inositides kinase; PLA2G6: phospholipase A2; PNPLA6: phospholipase B; PNPO: pyridox(am)ine 5'-phosphate oxidase; Ser: serine synthesis defects; SERAC1: serine active site containing protein 1; SNAP29: synaptosomal associated protein 29 KD; SNX14: sorting nexin 14 SV: synaptic vesicle; tRNAs: tRNA synthetases; TPP: thiamine pyrophosphate; VARS2 mt valyl-tRNA synthetases; VPS15 is also known as PHOSPHATIDYLINOSITOL 3-KINASE, REGULATORY SUBUNIT 4: PIK3R4; WDR45: WD repeat containing protein 45.