Abstract：
:Mitochondrial disease is hugely diverse with respect to associated clinical presentations and underlying genetic causes, with pathogenic variants in over 300 disease genes currently described. Approximately half of these have been discovered in the last decade due to the increasingly widespread application of next generation sequencing technologies, in particular unbiased, whole exome-and latterly, whole genome sequencing. These technologies allow more genetic data to be collected from patients with mitochondrial disorders, continually improving the diagnostic success rate in a clinical setting. Despite these significant advances, some patients still remain without a definitive genetic diagnosis. Large datasets containing many variants of unknown significance have become a major challenge with next generation sequencing strategies and these require significant functional validation to confirm pathogenicity. This interface between diagnostics and research is critical in continuing to expand the list of known pathogenic variants and concomitantly enhance our knowledge of mitochondrial biology. The increasing use of whole exome sequencing, whole genome sequencing and other "omics" techniques such as transcriptomics and proteomics will generate even more data and allow further interrogation and validation of genetic causes, including those outside of coding regions. This will improve diagnostic yields still further and emphasizes the integral role that functional assessment of variant causality plays in this process-the overarching focus of this review.
journal_name
J Inherit Metab Disjournal_title
Journal of inherited metabolic diseaseauthors
Thompson K,Collier JJ,Glasgow RIC,Robertson FM,Pyle A,Blakely EL,Alston CL,Oláhová M,McFarland R,Taylor RWdoi
10.1002/jimd.12104subject
Has Abstractpub_date
2020-01-01 00:00:00pages
36-50issue
1eissn
0141-8955issn
1573-2665journal_volume
43pub_type
杂志文章,评审abstract：:The mutation N370S accounts for 63% of the mutated glucocerebrosidase alleles of Portuguese type 1 Gaucher patients. It has been shown previously that this mutation is linked to the Pv1.1- form of the PvuII polymorphism and suggested that the N370S mutation in glucocerebrosidase alleles has an Ashkenazi Jewish origin....
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF00735401
更新日期：1994-01-01 00:00:00
abstract：:Mitochondrial diseases are usually severe and progressive conditions; however, there are rare forms that show remarkable spontaneous recoveries. Two homoplasmic mitochondrial tRNA mutations (m.14674T>C/G in mt-tRNA(Glu)) have been reported to cause severe infantile mitochondrial myopathy in the first months of life. I...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/s10545-014-9784-6
更新日期：2015-05-01 00:00:00
abstract：:In patients with cerebro-hepato-renal (Zellweger) syndrome, the absence of peroxisomes results in an impairment of metabolic processes in which peroxisomes are normally involved. These include the catabolism of very long chain (greater than C22) fatty acids, the biosynthesis of ether-phospholipids and of bile acids, t...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/BF01812845
更新日期：1987-01-01 00:00:00
abstract：:Early diagnosis and improved treatment are leading to the potential for increased reproductive capability in homocystinuria due to cystathionine beta-synthase (CbetaS) deficiency, but information about reproductive outcome and risk of thromboembolism in pregnancy is limited. To provide further information, clinical an...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/a:1016502408305
更新日期：2002-08-01 00:00:00
abstract：:Congenital disorders of glycosylation (CDG) are a rapidly growing family comprising >100 genetic diseases. Some 25 CDG are pure O-glycosylation defects. Even among this CDG subgroup, phenotypic diversity is broad, ranging from mild to severe poly-organ/system dysfunction. Ophthalmic manifestations are present in 60% o...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1002/jimd.12025
更新日期：2019-01-01 00:00:00
abstract：BACKGROUND:Cerebrotendinous xanthomatosis (CTX) is an autosomal recessively inherited inborn error of metabolism (IEM) due to mutations in the CYP27A1 gene. The clinical picture ranges from being nearly asymptomatic in early childhood, up to severe disability at adult age. Infantile-onset diarrhea and juvenile-onset ca...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-017-0086-7
更新日期：2018-07-01 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：:Neuropsychological assessment is essential in providing documentation of the untreated natural history of storage diseases associated with dementia and quantifying the effectiveness of treatment on central nervous system function. Baseline characterization and outcome of bone marrow transplantation (BMT) for three leu...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/BF00710053
更新日期：1995-01-01 00:00:00
abstract：OBJECTIVES:To study the incidence of galactosaemia in the state of São Paulo and the benefit/cost (B/C) ratio of the introduction of neonatal screening for galactosaemia, comparing it with a selective approach. METHODS:An enzymatic-colorimetric assay was used for the screening of total galactose (TG) in a sample of 10...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-009-1112-1
更新日期：2009-12-01 00:00:00
abstract：: ...
journal_title：Journal of inherited metabolic disease
pub_type： 评论,信件
doi：10.1007/s10545-018-0248-2
更新日期：2018-11-01 00:00:00
abstract：:Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is an autosomal recessive lysosomal storage disorder resulting from a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS) activity. Diagnosis can be challenging and requires agreement of clinical, radiographic, and laboratory findings. A group of bioc...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-013-9587-1
更新日期：2013-03-01 00:00:00
abstract：:Aspartylglycosaminuria (AGU) is a lysosomal storage disorder of glycoprotein degradation caused by deficiency of glycosylasparaginase (GA). A deletion mutation was found in a mildly affected AGU patient whose parents are first-cousins of Mauritian origin. One bp deletion at position 787 or 788 (delta T788) in exon 7 o...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01799351
更新日期：1996-01-01 00:00:00
abstract：:The lipid composition or the liver, spleen, brain, cerebellum and cerebrospinal fluid of a Gaucher disease type II patient who died at the age of 5 months was examined. The glycolipid analysis demonstrated a marked increase of total amounts not only in the peripheral tissues but also in the brain cerebellum and cerebr...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/a:1015137917508
更新日期：2002-02-01 00:00:00
abstract：:A new French-Canadian family from the province of Quebec is reported, in which a male child was diagnosed as hyperargininaemic after showing positive tests for cystinuria on neonatal screening. The child has no residual activity of erythrocyte arginase, and a plasma arginine level of 633 mumol/l. Both parents have 32-...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF02310878
更新日期：1983-01-01 00:00:00
abstract：:A 13.5-year-old boy with biotinidase deficiency was studied 8 days before and 5 months after biotin treatment by positron emission tomography (PET) and computerized electroencephalographic topography (CET). With biotin treatment there was a marked improvement in the presenting symptom of loss of visual acuity and a mo...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF00710288
更新日期：1993-01-01 00:00:00
abstract：:DNA sequence analyses have become a major component in the diagnostic work-up of patients; however, limited consideration appears to be given to the possibility that reported results may in fact be wrong. Over the last four years we have carried out an External Quality Assessment scheme for mutation analysis in phenyl...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-008-1052-1
更新日期：2008-12-01 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：:Mucopolysaccharidosis type III (MPS III) or Sanfilippo disease is an orphan inherited lysosomal storage disease and one of the most common MPS subtypes. The classical presentation is an infantile-onset neurodegenerative disease characterised by intellectual regression, behavioural and sleep disturbances, loss of ambul...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1002/jimd.12316
更新日期：2021-01-01 00:00:00
abstract：:In a series of 137 patients with methylmalonic acidaemia (MMA) and propionic acidaemia (PA) diagnosed since the early 1970s, we report in more detail 81 patients (51 MMA and 30 PA) diagnosed between 1988 and 2005. In this series, 14% of patients died at initial access revealing the disease before or despite treatment,...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-006-0351-7
更新日期：2006-04-01 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：:Multiple sulphatase deficiency was studied in 3 siblings--one pair of monozygotic twins and their sister. The children's psychomotor development was arrested at the age of 18 to 24 months, and the hypotonic syndrome combined with signs of spasticity appeared. There was marked hepatosplenomegaly, conspicuously dry scal...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01805620
更新日期：1984-01-01 00:00:00
abstract：:A severely mentally retarded infant with congenital lactic acidosis due to pyruvate carboxylase deficiency is reported. The patient suffered from vomiting and convulsions soon after birth and developed severe mental and motor retardation at 3 months of age. The persistent elevation of pyruvate and lactate in both bloo...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01800730
更新日期：1983-01-01 00:00:00
abstract：:Lyso-globotriaosylsphingosine (lyso-Gb3) is a useful biomarker in the diagnosis and monitoring of treatment for Fabry disease. However, it is unclear whether lyso-Gb3 is elevated in patients with later-onset Fabry disease. Thus, we measured lyso-Gb3 levels from dried blood spots (DBS) from male newborns with the Fabry...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-012-9547-1
更新日期：2013-09-01 00:00:00
abstract：:In most patients with deficiency of tetrahydrobiopterin (BH4) continuous administration of BH4 or of a synthetic analogue such as 6-methyltetrahydropterin (6-MPH4) lowers plasma phenylalanine concentrations to the therapeutic range. The effective dose of BH4 varies from 1 to 2 mg kg-1 daily in patients with defective ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01800658
更新日期：1985-01-01 00:00:00
abstract：: ...
journal_title：Journal of inherited metabolic disease
pub_type： 社论
doi：10.1007/s10545-018-00252-y
更新日期：2018-11-01 00:00:00
abstract：:A striking elevation of plasma chitotriosidase activity, greater than 150 times the normal median value, was found in two galactosialidosis patients. Furthermore, increased plasma chitotriosidase activity, 10-53 times the normal median value, was also observed in fucosidosis, glycogen storage disease type IV, Alagille...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/b:boli.0000043025.17721.fc
更新日期：2004-01-01 00:00:00
abstract：:It has been suggested that the very low incidence of atherosclerosis in glycogen storage disease type Ia (GSD Ia) subjects might be attributed to elevated levels of uric acid, one of the potent low molecular- weight antioxidants found in plasma. The present communication describes a use of two analytical methods-cycli...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-009-1242-5
更新日期：2009-10-01 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：:The content of coenzyme Q(10) (CoQ(10)) was examined in skin fibroblasts of 10 patients with mevalonic aciduria (MVA) and of 22 patients with methylmalonic aciduria (MMA). Patients with these inborn errors of metabolism are thought to be at risk for CoQ(10) depletion either by direct inhibition of the proximal pathway...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-009-1150-8
更新日期：2009-08-01 00:00:00
abstract：:Glycine encephalopathy, or nonketotic hyperglycinaemia (NKH; Mckusick 238300) is a severe autosomal recessive disease due to a defect in the glycine cleavage system (GCS), which is a complex of four subunits: P-, T-, H- and L-proteins. A P-protein (glycine decarboxylase or GLDC) deficiency was reported in about 80% of...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-006-0202-6
更新日期：2006-02-01 00:00:00
