PURPOSE: Gaucher disease is a common lysosomal storage disease that results from inherited mutations in the gene (GBA) encoding acid beta-glucosidase (GCase). Here, the clinical and molecular findings of the subacute neuronopathic variant are delineated among ethnic Poles. METHODS: Longitudinal studies of visceral, bony, and central nervous system involvement are delineated clinically. Complete gene GBA sequencing was used to characterize the mutations and haplotypes in this population. RESULTS: A greater frequency of subacute neuronopathic Gaucher disease (type 3) is present among ethnic Poles compared with other European countries. Two type 3 phenotypes were found: The first was an early-onset variant with massive visceral disease, progressive kyphoscoliosis, mild cognitive deficits, and survival for three or more decades. This variant resembles the "Norrbottnian" Swedish phenotype. The other variant had more severe progressive central nervous system disease, milder visceral involvement, and absence of kyphoscoliosis. Myoclonus was present in some patients. Neither variant had bone crises and/or pain as major components. The L444P/L444P genotype was most common, but on several different haplotype backgrounds. Other alleles encoded D409H, V305L, and E326K/A446P on various haplotypes. CONCLUSIONS: These studies provide additional expansion of the type 3 genotypes with some commonalities with and differences from other reported variants. Also, such phenotypic expansion should be expected in the other variants of Gaucher disease as the spectrum of ethnic variation becomes more fully delineated.
PURPOSE: Gaucher disease is a common lysosomal storage disease that results from inherited mutations in the gene (GBA) encoding acid beta-glucosidase (GCase). Here, the clinical and molecular findings of the subacute neuronopathic variant are delineated among ethnic Poles. METHODS: Longitudinal studies of visceral, bony, and central nervous system involvement are delineated clinically. Complete gene GBA sequencing was used to characterize the mutations and haplotypes in this population. RESULTS: A greater frequency of subacute neuronopathic Gaucher disease (type 3) is present among ethnic Poles compared with other European countries. Two type 3 phenotypes were found: The first was an early-onset variant with massive visceral disease, progressive kyphoscoliosis, mild cognitive deficits, and survival for three or more decades. This variant resembles the "Norrbottnian" Swedish phenotype. The other variant had more severe progressive central nervous system disease, milder visceral involvement, and absence of kyphoscoliosis. Myoclonus was present in some patients. Neither variant had bone crises and/or pain as major components. The L444P/L444P genotype was most common, but on several different haplotype backgrounds. Other alleles encoded D409H, V305L, and E326K/A446P on various haplotypes. CONCLUSIONS: These studies provide additional expansion of the type 3 genotypes with some commonalities with and differences from other reported variants. Also, such phenotypic expansion should be expected in the other variants of Gaucher disease as the spectrum of ethnic variation becomes more fully delineated.
Authors: A Vellodi; A Tylki-Szymanska; E H Davies; E Kolodny; B Bembi; T Collin-Histed; E Mengel; A Erikson; R Schiffmann Journal: J Inherit Metab Dis Date: 2009-08-05 Impact factor: 4.982
Authors: Nadia Sawicka-Gutaj; Maciej Machaczka; Izabela Kulińska-Niedziela; Jadwiga Bernardczyk-Meller; Paweł Gutaj; Jerzy Sowiński; Marek Ruchała Journal: Ups J Med Sci Date: 2016-04-11 Impact factor: 2.384