Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 3 de 3
Filter
1.
J Inherit Metab Dis ; 42(3): 451-458, 2019 05.
Article in English | MEDLINE | ID: mdl-30815886

ABSTRACT

Although movement disorders (MDs) are known complications, the exact frequency and severity remains uncertain in patients with classical galactosemia, especially in children. We determined the frequency, classification and severity of MDs in a cohort of pediatric and adult galactosemia patients, and assessed the association with nonmotor neuropsychological symptoms and daily functioning. Patients from seven centers in the United Kingdom and the Netherlands with a confirmed galactosemia diagnosis were invited to participate. A videotaped neurological examination was performed and an expert panel scored the presence, classification and severity of MDs. Disease characteristics, nonmotor neuropsychological symptoms, and daily functioning were evaluated with structured interviews and validated questionnaires (Achenbach, Vineland, Health Assessment Questionnaire, SIP68). We recruited 37 patients; 19 adults (mean age 32.6 years) and 18 children (mean age 10.7 years). Subjective self-reports revealed motor symptoms in 19/37 (51.4%), similar to the objective (video) assessment, with MDs in 18/37 patients (48.6%). The objective severity scores were moderate to severe in one third (6/37). Dystonia was the overall major feature, with additional tremor in adults, and myoclonus in children. Behavioral or psychiatric problems were present in 47.2%, mostly internalizing problems, and associated with MDs. Daily functioning was significantly impaired in the majority of patients. Only one patient received symptomatic treatment for MDs. We show that MDs and nonmotor neuropsychological symptoms are frequent in both children and adults with classical galactosemia.


Subject(s)
Behavioral Symptoms/diagnosis , Disability Evaluation , Galactosemias/complications , Galactosemias/diagnosis , Movement Disorders/diagnosis , Activities of Daily Living , Adolescent , Adult , Behavioral Symptoms/etiology , Child , Child, Preschool , Cohort Studies , Female , Humans , Male , Middle Aged , Movement Disorders/etiology , Netherlands , Psychometrics , Quality of Life , Severity of Illness Index , Surveys and Questionnaires , United Kingdom , Young Adult
2.
J Proteome Res ; 13(2): 385-94, 2014 Feb 07.
Article in English | MEDLINE | ID: mdl-24359113

ABSTRACT

Galactose intoxication and over-restriction in galactosemia may affect glycosylation pathways and cause multisystem effects. In this study, we describe an applied hydrophilic interaction chromatography ultra-performance liquid chromatography high-throughput method to analyze whole serum and extracted IgG N-glycans with measurement of agalactosylated (G0), monogalactosylated (G1), and digalactosylated (G2) structures as a quantitative measure of galactose incorporation. This was applied to nine children with severe galactosemia (genotype Q188R/Q188R) and one child with a milder variant (genotype S135L/S135L). The profiles were also compared with those obtained from three age-matched children with PMM2-CDG (congenital disorder of glycosylation type Ia) and nine pediatric control samples. We have observed that severe N-glycan assembly defects correct in the neonate following dietary restriction of galactose. However, treated adult galactosemia patients continue to exhibit ongoing N-glycan processing defects. We have now applied informative galactose incorporation ratios as a method of studying the presence of N-glycan processing defects in children with galactosemia. We identified N-glycan processing defects present in galactosemia children from an early age. For G0/G1, G0/G2, and (G0/G1)/G2 ratios, the difference noted between galactosemia patients and controls was found to be statistically significant (p = 0.002, 0.01, and 0.006, respectively).


Subject(s)
Galactosemias/metabolism , Polysaccharides/metabolism , Adolescent , Case-Control Studies , Child , Child, Preschool , Chromatography, Liquid/methods , Female , Humans , Infant , Male
3.
Genet Med ; 8(10): 620-7, 2006 Oct.
Article in English | MEDLINE | ID: mdl-17079878

ABSTRACT

PURPOSE: Oxidative phosphorylation is under dual genetic control of the nuclear and the mitochondrial DNA (mtDNA). Oxidative phosphorylation disorders are clinically and genetically heterogeneous, which makes it difficult to determine the genetic defect, and symptom-based protocols which link clinical symptoms directly to a specific gene or mtDNA mutation are falling short. Moreover, approximately 25% of the pediatric patients with oxidative phosphorylation disorders is estimated to have mutations in the mtDNA and a standard screening approach for common mutations and deletions will only explain part of these cases. Therefore, we tested a new CHIP-based screening method for the mtDNA. METHODS: MitoChip (Affymetrix) resequencing was performed on three test samples and on 28 patient samples. RESULTS: Call rates were 94% on average and heteroplasmy detection levels varied from 5-50%. A genetic diagnosis can be made in almost one-quarter of the patients at a potential output of 8 complete mtDNA sequences every 4 days. Moreover, a number of potentially pathogenic unclassified variants (UV) were detected. CONCLUSIONS: The availability of long-range PCR protocols and the predominance of single nucleotide substitutions in the mtDNA make the resequencing CHIP a very fast and reliable method to screen the complete mtDNA for mutations.


Subject(s)
DNA Mutational Analysis/methods , DNA, Mitochondrial/analysis , Genetic Testing/methods , Mitochondrial Diseases/diagnosis , Oligonucleotide Array Sequence Analysis , Child , DNA, Mitochondrial/genetics , Humans , Mutation , Nucleic Acid Conformation , Oxidative Phosphorylation , Polymerase Chain Reaction , RNA, Transfer/chemistry , RNA, Transfer/genetics
SELECTION OF CITATIONS
SEARCH DETAIL
...