PubMed Journal Database | Journal of inherited metabolic disease 
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Showing PubMed Articles 1–25 of 299 from Journal of inherited metabolic disease
Pathophysiology of fatty acid oxidation disorders and resultant phenotypic variability.
Fatty acids are a major fuel for the body and fatty acid oxidation is particularly important during fasting, sustained aerobic exercise and stress. The myocardium and resting skeletal muscle utilise long-chain fatty acids as a major source of energy. Inherited disorders affecting fatty acid oxidation seriously compromise the function of muscle and other highly energy-dependent tissues such as brain, nerve, heart, kidney and liver. Such defects encompass a wide spectrum of clinical disease, presenting in the...
Gastrointestinal and hepatic manifestations of mitochondrial disorders.
Inherited defects of oxidative phosphorylation lead to heterogeneous, often multisystem, mitochondrial diseases. This review highlights those mitochondrial syndromes with prominent gastrointestinal and hepatic symptoms, categorised according to underlying disease mechanism. Mitochondrial encephalopathies with major gastrointestinal involvement include mitochondrial neurogastrointestinal encephalopathy and ethylmalonic encephalopathy, which are each associated with highly specific clinical and metabolic prof...
BACKGROUND: Primary carnitine deficiency (PCD) is an autosomal recessive disorder of fatty acid oxidation and has been associated to episodes of sudden death in the Faroe Islands. Data are presented from the nationwide population based Faroese screening program to find people with low carnitine levels indicating PCD. METHODS: Whole blood samples from dried blood spots were analysed by tandem mass spectrometry with and without butylation. Genetic analyses were performed in all people with non-butylated free...
Human and mouse neuroinflammation markers in Niemann-Pick disease, type C1.
Niemann-Pick disease, type C1 (NPC1) is an autosomal recessive lipid storage disorder in which a pathological cascade, including neuroinflammation occurs. While data demonstrating neuroinflammation is prevalent in mouse models, data from NPC1 patients is lacking. The current study focuses on identifying potential markers of neuroinflammation in NPC1 from both the Npc1 mouse model and NPC1 patients. We identified in the mouse model significant changes in expression of genes associated with inflammation and c...
Mucopolysaccharide (MPS) diseases are lysosomal storage disorders (LSDs) caused by deficiencies in enzymes required for glycosaminoglycan (GAG) catabolism. Mucopolysaccharidosis I (MPS I), MPS IIIA, MPS IIIB and MPS VII are deficient in the enzymes α-L-Iduronidase, Heparan-N-Sulphatase, N-Acetylglucosaminidase and Beta-Glucuronidase, respectively. Enzyme deficiency leads to the progressive multi-systemic build-up of heparan sulphate (HS) and dermatan sulphate (DS) within cellular lysosomes, followed by cel...
Does the PKU diet contribute to impaired renal function?
The blood-brain barrier friend or foe?
Early cardiovascular remodelling in Fabry disease.
AIMS: Fabry disease (FD) is a rare X-linked genetic disorder caused by the deficiency or absent activity of lysosomal α-galactosidase A. Cardiovascular remodelling is a hallmark of FD. The present study aimed to comprehensively evaluate the cardiac, vascular and microvascular status in a population of patients with genetic mutations for FD without left ventricular hypertrophy (LVH). METHODS AND RESULTS: This study includes subjects carrying genetic mutations for FD (Fabry disease mutation-carrier, FDMC) wi...
The brain in late-onset glycogenosis II: a structural and functional MRI study.
BACKGROUND: Late-onset glycogenosis type II (GSD II) is a rare, multisystem disorder mainly affecting limb and respiratory muscles due to acid alpha glucosidase deficiency. Despite evidence at autopsy of glycogen accumulation in the brain, no study exploring brain functions is yet available. OBJECTIVE: Our objective in this study was to assess brain changes in late-onset GSD II. METHODS: Each patient underwent a standardized neuropsychological assessment, regional grey-matter (GM) atrophy, and resting-state...
Blood-brain barrier structure and function and the challenges for CNS drug delivery.
The neurons of the central nervous system (CNS) require precise control of their bathing microenvironment for optimal function, and an important element in this control is the blood-brain barrier (BBB). The BBB is formed by the endothelial cells lining the brain microvessels, under the inductive influence of neighbouring cell types within the 'neurovascular unit' (NVU) including astrocytes and pericytes. The endothelium forms the major interface between the blood and the CNS, and by a combination of low pas...
Glutathione metabolism in cobalamin deficiency type C (cblC).
BACKGROUND: Methylmalonic aciduria with homocystinuria, cblC defect, is the most frequent disorder of vitamin B12 metabolism. CblC patients are commonly treated with a multidrug therapy to reduce metabolite accumulation and to increase deficient substrates. However the long-term outcome is often unsatisfactory especially in patients with early onset, with frequent progression of neurological and ocular impairment. Recent studies, have shown perturbation of cellular redox status in cblC. To evaluate the pote...
Phenylketonuria (PKU, OMIM 261600) is an autosomal recessive inborn error of phenylalanine metabolism, predominantly caused by mutations in the phenylalanine hydroxylase (PAH) gene. Approximately 10 % of patients carry a nonsense mutation, which results in an inactive or unstable truncated protein. In some genetic disorders, including cystic fibrosis and Duchenne muscular dystrophy, restoration of full-length protein has been achieved by aminoglycoside antibiotics, such as gentamicin and G-418 (Geneticin)....
Current concepts in organic acidurias: understanding intra- and extracerebral disease manifestation.
This review focuses on the pathophysiology of organic acidurias (OADs), in particular, OADs caused by deficient amino acid metabolism. OADs are termed classical if patients present with acute metabolic decompensation and multiorgan dysfunction or cerebral if patients predominantly present with neurological symptoms but without metabolic crises. In both groups, however, the brain is the major target. The high energy demand of the brain, the gate-keeping function of the blood-brain barrier, a high lipid conte...
BACKGROUND: Effectiveness of enzyme replacement therapy (ERT) in reverting hematologic, skeletal, and visceral symptoms in Gaucher disease (GD) has been demonstrated, although, its efficacy in neurologic involvement is still debated. AIM: We evaluated the extent of neuro-cognitive dysfunction using brain stem evoked potential in GD3 patients, age-matched controls, and GD1 patients without neurological manifestations served as disease control group. METHODS: Study included 56 GD (36 had type 1, 20 had type 3...
Impact of new screening technologies: should we screen and does phenotype influence this decision?
The early detection offered by newborn screening for phenylketonuria clearly demonstrates the benefits for patients with inherited metabolic disorders of well organised screening programmes. It is therefore perhaps surprising that 20 years after the introduction of electrospray MS/MS methods to support expanded newborn screening that considerable international variation in practice, not linked to economic factors, exists. It is likely that the commonly used criteria to assess the suitability of a disorder...
An update on serine deficiency disorders.
Serine deficiency disorders are caused by a defect in one of the three synthesising enzymes of the L-serine biosynthesis pathway. Serine deficiency disorders give rise to a neurological phenotype with psychomotor retardation, microcephaly and seizures in newborns and children or progressive polyneuropathy in adult patients. There are three defects that cause serine deficiency of which 3-phosphoglycerate dehydrogenase (3-PGDH) deficiency, the defect affecting the first step in the pathway, has been reported...
Retinal characteristics of the congenital disorder of glycosylation PMM2-CDG.
The congenital disorder of glycosylation, PMM2-CDG, is associated with progressive photoreceptor degeneration, which causes a pigmentary retinopathy. We identified a sibling pair, mildly affected with PMM2-CDG, who showed preserved photoreceptor function, but profound deficits of the 'on-pathway' in the retina. This localises the site of early, or initial, retinal dysfunction in PMM2-CDG to the synapse in the outer plexiform layer between bipolar cells, photoreceptors and horizontal cells. We sought wider e...
A structural mapping of mutations causing succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency.
Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency is a rare inherited metabolic disorder of ketone metabolism, characterized by ketoacidotic episodes and often permanent ketosis. To date there are ∼20 disease-associated alleles on the OXCT1 gene that encodes the mitochondrial enzyme SCOT. SCOT catalyzes the first, rate-limiting step of ketone body utilization in peripheral tissues, by transferring a CoA moiety from succinyl-CoA to form acetoacetyl-CoA, for entry into the tricarboxylic acid cycle f...
Niemann-Pick type C disease is an inherited autosomal recessive neurodegenerative disorder characterised by the accumulation of unesterified cholesterol and sphingolipids within the endosomal/lysosomal compartments. It has been observed that the administration of hydroxypropyl-β-cyclodextrin (HPBCD) delays onset of clinical symptoms and reduces accumulation of cholesterol and gangliosides within neuronal cells. It was assumed that HPBCD exerts its action by readily entering the CNS and directly interacting...
OBJECTIVE: To analyse diagnostic value of somato-sensory evoked potentials (SEP), magnetic resonance imaging (MRI), and clinical neurological examination in the decision for decompression surgery in mucopolysaccharidosis (MPS) VI patients with craniocervical cord compression (CCJ). METHODS: We retrospectively analysed neurological examination, SEP of the median nerve and MRI outcomes from 31 MPS VI patients. Individual scores for each test (based on severity of findings) and a sum of scores of all three pro...
Hypertrichosis in presymptomatic mitochondrial disease.
Leigh syndrome is a neurometabolic disorder commonly associated with disturbed oxidative phosphorylation, which leads to bilateral symmetric necrotizing lesions in the central nervous system. Neurological symptoms may be accompanied by cutaneous abnormalities. Here, we present images of distinct hypertrichosis in an otherwise asymptomatic one-year-old patient with pathogenic SURF1 gene mutations. We conclude that, if Leigh syndrome is suspected, the presence of characteristic hypertrichosis should prompt SU...
Nearly all children with MPS IVA develop skeletal deformities affecting the spine. At the atlanto-axial spine, odontoid hypoplasia occurs. GAG deposition around the dens, leads to peri-odontoid infiltration. Transverse/alar ligament incompetence causes instability. Atlanto-axial instability is associated with cord compression and myelopathy, leading to major morbidity and mortality. Intervention is often required. Does the presence of widened bullet shaped vertebra in platyspondily encroach on the spinal ca...
Rett syndrome is a neurodevelopmental disorder characterized by cognitive and locomotor regression and stereotypic hand movements. The disorder is caused by mutations in the X chromosomal MECP2 a gene encoding methyl CpG-binding protein. It has been associated with disturbances of cerebral folate homeostasis, as well as with speculations on a compromised DNA-methylation. Folinic acid is the stable form of folate. Its derived intermediate 5-MTHF supports the conversion of homocysteine to methionine, the prec...
BACKGROUND: The mucopolysaccharide disorders (MPS) are a group of recessively inherited metabolic disorders resulting in progressive physical and cognitive decline. MATERIALS AND METHODS: MEDLINE, PsycINFO and Embase databases were searched, alongside manual screening, to identify relevant literature. Papers were included in the review if they were published in a peer reviewed journal and conducted empirical research into cognitive, motor, social or linguistic development or behaviour in one or more MPS dis...
