RESUMO
OBJECTIVE: To evaluate the clinical presentation of patients with GM1 gangliosidosis and to determine whether specific clinical or biochemical signs could lead to a prompt diagnosis. STUDY DESIGN: We retrospectively analyzed clinical, biochemical, and genetic data of 22 patients with GM1 gangliosidosis from 5 metabolic centers in Germany and Austria. RESULTS: Eight patients were classified as infantile, 11 as late-infantile, and 3 as juvenile form. Delay of diagnosis was 6 ± 2.6 months in the infantile, 2.6 ± 3.79 years in the late-infantile, and 14 ± 3.48 years in the juvenile form. Coarse facial features, cherry red spots, and visceromegaly occurred only in patients with the infantile form. Patients with the late-infantile and juvenile forms presented with variable neurologic symptoms. Seventeen patients presented with dystonia and 14 with dysphagia. Laboratory analysis revealed an increased ASAT concentration (13/20), chitotriosidase activity (12/15), and pathologic urinary oligosaccharides (10/19). Genotype analyses revealed 23 causative or likely causative mutations in 19 patients, 7 of them being novel variants. In the majority, a clear genotype-phenotype correlation was found. CONCLUSIONS: Diagnosis of GM1 gangliosidosis often is delayed, especially in patients with milder forms of the disease. GM1 gangliosidosis should be considered in patients with progressive neurodegeneration and spastic-dystonic movement disorders, even in the absence of visceral symptoms or cherry red spots. ASAT serum concentrations and chitotriosidase activity may be of value in screening for GM1 gangliosidosis.
Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , DNA/genética , Gangliosidose GM1/genética , Mutação , beta-Galactosidase/genética , Adolescente , Áustria/epidemiologia , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Seguimentos , Gangliosidose GM1/diagnóstico , Gangliosidose GM1/epidemiologia , Genótipo , Alemanha/epidemiologia , Humanos , Incidência , Lactente , Masculino , Fenótipo , Estudos Retrospectivos , Adulto Jovem , beta-Galactosidase/metabolismoRESUMO
OBJECTIVE: To investigate effects of long-chain omega-3 polyunsaturated fatty acids (LC-PUFA) on motor skills in patients with phenylketonuria (PKU). STUDY DESIGN: Thirty-six patients with PKU (1-11 years of age, good metabolic control: plasma phenylalanine < or = 360 micromol/L for > or = 6 months). We determined plasma phospholipid fatty acids, and in patients > 4 years of age (N = 24) the motometric Rostock-Oseretzky Scale (ROS), before and after supplementation with fish oil for 3 months (15 mg docosahexaenoic acid [DHA]/kg body weight daily). ROS was also assessed in 22 age-matched controls. RESULTS: Patients had low n-3 LC-PUFA in plasma phospholipids (DHA, 2.37 +/- 0.10%; eicosapentaenoic acid [EPA], 0.4 +/- 0.03%) and poorer ROS performance than controls (motor development index [MQ] 107 +/- 3 vs 117 +/- 3, P = .010). Supplementation increased phospholipid n-3 LC-PUFA (DHA 7.05 +/- 0.24%; EPA 3.31 +/- 0.19%; P < .001), decreased n-6 LC-PUFA (arachidonic acid, 9.26 +/- 0.23% vs 6.76 +/- 0.16%; P < .001) and improved ROS (MQ 115 +/- 3.54, P = .011, paired t test). ROS was unchanged in 11 retested controls (MQ 115 +/- 5.16, P = NS, paired t test multivariate analysis of variance [MANOVA] for time by group, P = .027). Patients tolerated fish oil well. Plasma phenylalanine remained unchanged. CONCLUSION: In patients with PKU, fish oil supplementation enhances n-3 LC-PUFA levels and improves motor skills.