Abstract：
:We report a new constellation of clinical features consisting of hypermanganesaemia, liver cirrhosis, an extrapyramidal motor disorder and polycythaemia in a 12 year-old girl born to consanguineous parents. Blood manganese levels were >3000 nmol/L (normal range <320 nmol/L) and MRI revealed signal abnormalities of the basal ganglia consistent with manganese deposition. An older brother with the same phenotype died at 18 years, suggesting a potentially lethal, autosomal recessive disease. This disorder is probably caused by a defect of manganese metabolism with the accumulation of manganese in the liver and the basal ganglia similar to the copper accumulation in Wilson disease. In order to assess the genetic basis of this syndrome we investigated two candidate genes: ATP2C2 and ATP2A3 encoding the manganese-transporting calcium-ATPases, SPCA2 and SERCA3, respectively. Genotyping of the patient and the family for microsatellite markers surrounding ATP2C2 and ATP2A3 excluded these genes. The patient was found to be heterozygous for both gene loci. Despite the unknown pathophysiology, we were able to develop a successful treatment regime. Chelation therapy with disodium calcium edetate combined with iron supplementation is the treatment of choice, lowering blood manganese levels significantly and improving clinical symptoms.
journal_name
J Inherit Metab Disjournal_title
Journal of inherited metabolic diseaseauthors
Tuschl K,Mills PB,Parsons H,Malone M,Fowler D,Bitner-Glindzicz M,Clayton PTdoi
10.1007/s10545-008-0813-1subject
Has Abstractpub_date
2008-04-01 00:00:00pages
151-63issue
2eissn
0141-8955issn
1573-2665journal_volume
31pub_type
杂志文章abstract：:Twenty-four pregnancies at risk for Hurler disease (MPS I) were monitored by measurement of alpha-iduronidase in chorionic villi. Adequate samples were obtained for direct assay of the villi in 22 pregnancies. Five were found to be affected and the pregnancies were terminated. In another pregnancy an equivocal result ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01799636
更新日期：1992-01-01 00:00:00
abstract：:In the light of clinical experience in infantile onset Pompe patients, the immunological impact on the tolerability and long-term efficacy of enzyme replacement therapy (ERT) for lysosomal storage disorders has come under renewed scrutiny. This article details the currently proposed immunological mechanisms involved i...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/s10545-016-9917-1
更新日期：2016-07-01 00:00:00
abstract：:The mitochondrial myopathies or encephalomyopathies with known biochemical defects can be divided into 5 groups: (1) defects of mitochondrial transport, such as CPT deficiency or carnitine deficiencies; (2) defects of substrate utilization, such as PDHC deficiency or defects of beta-oxidation; (3) defects of the Krebs...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/BF01812852
更新日期：1987-01-01 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：BACKGROUND:Recent decades have unravelled the molecular background of a number of inborn errors of metabolism (IEM) causing vitamin B6-dependent epilepsy. As these defects interfere with vitamin B6 metabolism by different mechanisms, the plasma vitamin B6 profile can give important clues for further molecular work-up. ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-016-9955-8
更新日期：2016-09-01 00:00:00
abstract：:Lesch-Nyhan disease (LND) is caused by complete deficiency of the hypoxanthine-guanine phosphoribosyltransferase enzyme. It is characterized by overproduction of uric acid, jointly with severe motor disability and self-injurious behaviour which physiopathology is unknown. These neurological manifestations suggest a dy...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-012-9470-5
更新日期：2012-11-01 00:00:00
abstract：:Electron micrographs of fibroblasts of an HHH-syndrome patient showed abnormal structures, similar, but not identical, to those observed in the liver of such patients. It is suggested that incorporation of a mutated protein into the inner mitochondrial membrane gives rise to a rearrangement of that membrane, resulting...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01805595
更新日期：1984-01-01 00:00:00
abstract：:Hydroxyproline has the same integer molecular weight as leucine and isoleucine and is quantified with these by tandem mass spectrometry. An infant was diagnosed with hyperhydroxyprolinaemia following further evaluation of an elevated "leucine" level in newborn screening by tandem mass spectrometry. ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/b:boli.0000045839.08631.9d
更新日期：2004-01-01 00:00:00
abstract：:Cerebrotendinous xanthomatosis (CTX) OMIM#213700 is a rare disorder of bile acid synthesis caused by deficiency of the enzyme sterol 27-hydroxylase. It results in deficiency of bile acids and accumulation of abnormal bile alcohols and accelerated cholesterol synthesis. CTX usually presents in the second or third decad...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-008-0815-z
更新日期：2008-12-01 00:00:00
abstract：:The extent of hydroxylation of proline in collagen synthesized and secreted into the culture medium by skin fibroblasts derived from a patient with prolidase deficiency has been examined and found to be normal. It would seem likely that to a considerable extent the urinary proline-containing dipeptides apparent in thi...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01800003
更新日期：1982-01-01 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：:Glycogen storage disease type Ib (GSD-Ib) is caused by a deficiency in the ubiquitously expressed glucose-6-phosphate (G6P) transporter (G6PT or SLC37A4). The primary function of G6PT is to translocate G6P from the cytoplasm into the lumen of the endoplasmic reticulum (ER). Inside the ER, G6P is hydrolyzed to glucose ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/s10545-018-0180-5
更新日期：2018-11-01 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：:Thirty patients with early and continuously treated phenylketonuria (PKU) between 8 and 20 years of age were compared with 30 controls, matched individually for age, sex, and educational level of both parents, on behaviour rating scales for parents and teachers as well as a school achievement scale. PKU patients, as a...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/a:1005669610722
更新日期：2000-09-01 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：:Fabry disease (McKusick 301500) is an X-linked lysosomal storage disorder due to deficient alpha-galactosidase A activity, which leads to accumulation of glycosphingolipids, especially in vascular smooth-muscle and endothelial cells. The effect of this accumulation on peripheral and cardiac vascular function is poorly...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-005-0563-2
更新日期：2005-01-01 00:00:00
abstract：:We measured the activities of two major forms of alpha-glucosidase in lymphocytes and cultured fibroblasts from normal healthy controls and patients with Pompe's disease by using 4-methylumbelliferyl-alpha-D-glucoside as substrate. We found (1) enzyme activity of the pH 4 and pH 6 forms varied with age, and (2) patien...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01799482
更新日期：1987-01-01 00:00:00
abstract：:Aldolase B is critical for sugar metabolism, and a catalytic deficiency due to mutations in its gene may result in hereditary fructose intolerance (HFI) syndrome, with hypoglycaemia and severe abdominal symptoms. This report describes two cases of HFI, which were identified by intravenous fructose tolerance test and a...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/a:1022043307569
更新日期：2002-11-01 00:00:00
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 includ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/s10545-018-0235-7
更新日期：2018-11-01 00:00:00
abstract：:Pyrroline-5-carboxylate reductase 1 (PYCR1) catalyzes the last step in proline synthesis. Deficiency of PYCR1, caused by a defect in PYCR1, was recently described in patients with cutis laxa, intrauterine growth retardation, developmental dysplasia of the hips and mental retardation. In this paper, we describe additio...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-011-9319-3
更新日期：2011-06-01 00:00:00
abstract：:Studies on fibroblasts from patients with lactic acidosis of different causes showed secondary metabolic changes in pathways of glucose metabolism. These secondary changes may be important clues to the diagnosis of the many different types of hereditary lactic acidosis. ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01805587
更新日期：1978-01-01 00:00:00
abstract：:A new variant of glycogen storage disease (GSD) Type 1, with clinical symptoms and laboratory findings consistent with those of glucose-6-phosphatase (G6Pase) deficiency, is described. Assay of G6Pase in liver from the patient immediately after biopsy by the method of Nordlie and Arion gave low activity (0.8 mumol/min...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01801717
更新日期：1980-01-01 00:00:00
abstract：:Patients with Fabry disease frequently develop left ventricular (LV) hypertrophy and renal fibrosis. Due to heat intolerance and an inability to sweat, patients tend to avoid exposure to sunlight. We hypothesized that subsequent vitamin D deficiency may contribute to Fabry cardiomyopathy. This study investigated the v...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-013-9653-8
更新日期：2014-03-01 00:00:00
abstract：:Recently a striking elevation of the activity of chitotriosidase, an endo beta-glucosaminidase distinct from lysozyme, was found in plasma from patients with Gaucher type I disease (McKusick 230800). Plasma chitotriosidase originates from activated macrophages and this elevation is secondary to the basic defect in Gau...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF02436762
更新日期：1995-01-01 00:00:00
abstract：:The carnitine ester spectrum was studied using ESI tandem mass spectrometry in a 2.5-year-old male Roma child with homozygous deletion of 844C of the SLC22A5 gene, presenting with hepatopathy and cardiomyopathy. Besides the dramatic decrease of plasma free carnitine (1.38 vs 32.7 mumol/L in controls) all plasma carnit...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-009-0926-1
更新日期：2009-12-01 00:00:00
abstract：:Ultrastructural study of skin biopsies in two cases of Gaucher disease (GD) patients (types II and III) revealed hitherto unknown alteration of the blood capillary endothelial cells (ECs) featured by hypertrophy and numerous subplasmalemmal microvesicles underneath both the apical and basal membranes. There was also p...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-009-9018-5
更新日期：2010-02-01 00:00:00
abstract：:This study aimed to evaluate systematically the effect of the free use of fruits and vegetables containing an intermediate amount of phenylalanine (51-100 mg/100 g) on the biochemical control in children with phenylketonuria (PKU). Fifteen subjects with PKU, with a median age of 6 years (range 1-24 years) were studied...
journal_title：Journal of inherited metabolic disease
pub_type： 临床试验,杂志文章
doi：10.1023/a:1025150901439
更新日期：2003-01-01 00:00:00
abstract：:Glycogen storage disease type 1a (von Gierke disease, GSD1a) is caused by the deficiency of microsomal glucose-6-phosphatase (G6Pase) activity. The cloning of G6Pase cDNA and characterization of the human G6Pase gene enabled the identification of the mutations causing GSD1a. Here we report on the clinical and biochemi...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/a:1005445802822
更新日期：1999-04-01 00:00:00
abstract：:We measured L-ornithine oxidation in cultured skin fibroblasts from seven patients with hyperornithinaemia-hyperammonaemia-homocitrullinuria (HHH) syndrome (McKusick 23897), and compared it with oxidation by ornithine aminotransferase deficient gyrate atrophy (McKusick 25887) cells and lysinuric protein intolerance (M...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01805528
更新日期：1989-01-01 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
