Abstract：
:Impaired activity of galactose-1-phosphate uridyltransferase (GALT) causes galactosemia, an autosomal recessive disorder of galactose metabolism. Early initiation of a galactose-restricted diet can prevent or resolve neonatal complications. Despite therapy, patients often experience long-term complications including speech impairment, learning disabilities, and premature ovarian insufficiency in females. This study evaluates clinical outcomes in 34 galactosemia patients with markedly reduced GALT activity and compares outcomes between patients with different levels of mean galactose-1-phosphate in red blood cells (GAL1P) using logistic regression: group 1 (n = 13) GAL1P ≤1.7 mg/dL vs. group 2 (n = 21) GAL1P ≥ 2 mg/dL. Acute symptoms at birth were comparable between groups (p = 0.30) with approximately 50% of patients presenting with jaundice, liver failure, and failure-to-thrive. However, group 2 patients had significantly higher prevalence of negative long-term outcomes compared to group 1 patients (p = 0.01). Only one of 11 patients >3 yo in group 1 developed neurological and severe behavioral problems of unclear etiology. In contrast, 17 of 20 patients >3 yo in group 2 presented with one or more long-term complications associated with galactosemia. The majority of females ≥15 yo in this group also had impaired ovarian function with markedly reduced levels of anti-Müllerian hormone. These findings suggest that galactosemia patients with higher GAL1P levels are more likely to have negative long-term outcome. Therefore, evaluation of GAL1P levels on a galactose-restricted diet might be helpful in providing a prognosis for galactosemia patients with rare or novel genotypes whose clinical presentations are not well known.
journal_name
J Inherit Metab Disjournal_title
Journal of inherited metabolic diseaseauthors
Yuzyuk T,Viau K,Andrews A,Pasquali M,Longo Ndoi
10.1007/s10545-018-0136-9subject
Has Abstractpub_date
2018-03-01 00:00:00pages
197-208issue
2eissn
0141-8955issn
1573-2665pii
10.1007/s10545-018-0136-9journal_volume
41pub_type
杂志文章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：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：:A female patient with isovaleric acidaemia had a successful outcome from pregnancy. ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/a:1022837416232
更新日期：2002-12-01 00:00:00
abstract：:Employing lymphoblasts derived from two non related patients with L-2-HG aciduria, we examined the origin of L-2-hydroxyglutaric acid (L-2-HG) through incubation with [(13)C6]glucose and [(2)H5]glutamic acid. Formation of labelled 2-ketoglutaric acid (2-KG), citric acid and L-2-HG was determined by GC-MS. The quantita...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-007-0697-5
更新日期：2007-10-01 00:00:00
abstract：:Phosphatidylethanolamine plasmalogen levels were determined in erythrocytes from controls and 13 patients with the cerebro-hepato-renal (Zellweger) syndrome. It was found that in Zellweger patients 20 weeks of age or younger, erythrocyte phosphatidylethanolamine plasmalogen levels were lowered whereas in older patient...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01800482
更新日期：1986-01-01 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：:We report a 5-year-old child carrying polymerase gamma (POLG1) mutations, but strikingly normal oxidative phosphorylation analysis in muscle, fibroblasts and liver. Mutations in POLG1 have so far been described in children with severe combined oxidative phosphorylation (OXPHOS) deficiencies and with the classical Alpe...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-008-0871-4
更新日期：2008-12-01 00:00:00
abstract：:The transmembrane domain recognition complex (TRC) targets cytoplasmic C-terminal tail-anchored (TA) proteins to their respective membranes in the endoplasmic reticulum (ER), Golgi, and mitochondria. It is composed of three proteins, GET4, BAG6, and GET5. We identified an individual with compound heterozygous missense...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1002/jimd.12249
更新日期：2020-09-01 00:00:00
abstract：:Twin brothers were born with clinical symptoms indicating that they were suffering from Zellweger syndrome. However, instead of a generalized peroxisomal dysfunction, only very long-chain fatty acids and the pristanic acid/phytanic acid ratio were elevated in plasma and decreased oxidation of very long-chain fatty aci...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/a:1005318308422
更新日期：1997-09-01 00:00:00
abstract：:Lysinuric protein intolerance (LPI) is a disorder of dibasic amino acid transport secondary to mutation of the SLC7A7 gene characterized by renal failure, pulmonary alveolar proteinosis, lupus-like autoimmune symptoms and usually increased plasma citrulline. In order to better understand the underlying mechanism, we s...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-005-5954-x
更新日期：2005-01-01 00:00:00
abstract：BACKGROUND:Cerebrotendinous xanthomatosis (CTX) is a rare genetic disorder, characterised by chronic diarrhoea, xanthomas, cataracts, and neurological deterioration. CTX is caused by CYP27A1 deficiency, which leads to abnormal cholesterol and bile acid metabolism. Urinary bile acid profiling (increased m/z 627: glucuro...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1002/jimd.12219
更新日期：2020-07-01 00:00:00
abstract：:We present a 32-year-old patient who, from age 7 months, developed photophobia, left-eye ptosis and progressive muscular weakness. At age 7 years, she showed normal psychomotor development, bilateral ptosis and exercise-induced weakness with severe acidosis. Basal blood and urine lactate were normal, increasing dramat...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-010-9169-4
更新日期：2010-12-01 00:00:00
abstract：:6-Methyluracil (6MU) has been identified in urine collected during acute illness in two children with beta-ketothiolase deficiency (approximately 1 mmol/L) and in two children with recurrent infection-related ketoacidaemia of unknown aetiology (levels of 6.3 and 7.1 mmol/mmol creatinine). Significant amounts of 6MU we...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF00735400
更新日期：1994-01-01 00:00:00
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 gen...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1002/jimd.12104
更新日期：2020-01-01 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：:Primary hyperoxaluria type I (PH1) is a rare disease caused by the deficit of liver alanine-glyoxylate aminotransferase (AGT). AGT prevents oxalate formation by converting peroxisomal glyoxylate to glycine. When the enzyme is deficient, progressive calcium oxalate stones deposit first in the urinary tract and then at ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-017-0105-8
更新日期：2018-03-01 00:00:00
abstract：:Low-density lipoprotein receptor (LDLR) is a cell-surface glycoprotein that mediates specific uptake and catabolism of plasma LDL. Mutations located in the coding region of the LDLR gene affect the structure and function of the protein and cause familial hypercholesterolaemia (FH). Mutations in the regulatory regions ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/B:BOLI.0000037337.93335.c4
更新日期：2004-01-01 00:00:00
abstract：:Defects in a pathway as complex as the electron transport chain cause a variety of clinical abnormalities, which vary from fatal lactic acidosis in infancy to mild muscle disease in adults. The primary defect may reside in the nucleus or the mitochondrial genome. Until relatively recently, biochemical assays were the ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/BF01799107
更新日期：1996-01-01 00:00:00
abstract：:Cloning of the gene defective in the X-linked neurodegenerative disorder Menkes disease led to a cascade of new findings. Besides giving a better understanding of the intracellular copper homeostasis, these findings had important consequences from a clinical point of view. Today the underlying genetic defect has been ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1023/a:1005479307906
更新日期：1998-08-01 00:00:00
abstract：:This review surveys the potential application of gene therapy to metabolic diseases. Proof of principle has been achieved in the treatment of two inherited immunodeficiency conditions. A significant safety issue has also been observed. Several strategies are being experimentally tested for a number of metabolic diseas...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/s10545-006-0270-7
更新日期：2006-04-01 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：:This study reports three novel mutations of the methionine adenosyltransferase (MAT) lA gene and confirms that hyperhomocysteinaemia may be a characteristic finding in MAT I/III deficiency. Thus, MAT I/III deficiency is important in the differential diagnoses of hyperhomocysteinaemia, which may lead to clinical compli...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-005-4497-5
更新日期：2005-01-01 00:00:00
abstract：BACKGROUND:Hearing loss (HL) is a well-known feature of Fabry disease (FD). Its presence and characteristics have mainly been studied in adult patients, while only limited data are available on the presence and degree of HL in children with FD. This prompted us to study hearing sensitivity in pediatric FD patients. ME...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-017-0051-5
更新日期：2017-09-01 00:00:00
abstract：BACKGROUND:Arginase 1 (ARG1) deficiency is a rare urea cycle disorder (UCD). This hypothesis-generating study explored clinical phenotypes, metabolic profiles, molecular genetics, and treatment approaches in a cohort of children and adults with ARG1 deficiency to add to our understanding of the underlying pathophysiolo...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-016-9928-y
更新日期：2016-05-01 00:00:00
abstract：:Carnitine transporter deficiency (CTD) and holocarboxylase synthetase deficiency (HLCSD) are frequent in The Faroe Islands compared to other areas, and treatment is available for both disorders. In order to evaluate the feasibility of neonatal screening in The Faroe Islands we studied detection in the neonatal period ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-007-0527-9
更新日期：2007-06-01 00:00:00
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：:We report studies on two patients (1 and 2) with Hurler disease. They both had all of the non-neurological features of Hurler disease to a similar and extreme degree and similar signs of brain damage on computed tomography. However, intellectual function was unusually well-preserved in patient 1, but seriously and typ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01799658
更新日期：1986-01-01 00:00:00
abstract：:We report the case of a boy with 5,10-methylenetetrahydrofolate reductase deficiency. The clinical features consisted of severe mental retardation, spasticity and seizures remaining static to 7 years of age followed by a phase of rapid deterioration and death at 7 1/2 years of age. The main biochemical findings were h...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01801662
更新日期：1985-01-01 00:00:00
abstract：:The inheritance of Crigler-Najjar type II disease is still contested. Autosomal dominant transmission with incomplete penetrance and autosomal recessive transmission have been proposed. We had the opportunity to study the hepatic activity of bilirubin uridinediphosphate glucuronyltransferase in parents whose first chi...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01799221
更新日期：1989-01-01 00:00:00
abstract：:We report a Brazilian girl who was diagnosed as having galactosialidosis (deficiency of protective protein/cathepsin A; PPCA deficiency; GS) at the age of 2 years 6 months during an extensive investigation for renal failure. She was found to have low levels of both β-galactosidase and α-neuraminidase in fibroblasts an...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-008-0730-3
更新日期：2008-12-01 00:00:00
