Neuronopathic Gaucher disease: demographic and clinical features of 131 patients enrolled in the International Collaborative Gaucher Group Neurological Outcomes Subregistry

Abstract

Neurological manifestations of GD often begin to appear before the age of 2 years. The most common neurological signs and manifestations are brainstem abnormalities and fine motor dysfunction. The most common genotype is L444P/L444P.

Characteristics of 27 patients with type 3 Gaucher disease: a descriptive analysis from the Gaucher Outcome Survey

“…Most of the patients with GD3 in this study had a GBA1 genotype of L444P/L444P (16/23; 69.6%), which is associated with neuronopathic GD and is at a rate consistent with previous ICGG Gaucher registry reports [4,10,26]. Although genotype-phenotype correlations are not absolute, and many patients with the L444P mutation are phenotypically similar to GD1, its presence is associated with increased disease severity and can help differentiate between type 1 and type 3 disease [20].…”

“…The clinical presentation of patients with GD3 is diverse, ranging from aggressive systemic involvement, including enlarged liver and spleen, anemia, thrombocytopenia, bone manifestations including kyphosis, infiltrative lung disease [10], and early onset of horizontal supranuclear gaze palsy (type 3b), to predominant neurological involvement, including cognitive impairment, saccadic eye movement abnormalities, auditory processing defects, seizures, muscle weakness, ataxia and, in some cases, a progressive myoclonic epilepsy (type 3a) [10][11][12]. A distinct form of GD3 (type 3c) is linked to a particular genotype (D409H homozygosity) and manifests with corneal opacity and valvular heart disease with progressive calcification [13].…”

“…A distinct form of GD3 (type 3c) is linked to a particular genotype (D409H homozygosity) and manifests with corneal opacity and valvular heart disease with progressive calcification [13]. Neurological manifestations may arise at any age, although nearly half experience onset before 2 years of age [10]. Universal clinical findings include eye movement disorder, either presenting as oculomotor apraxia in younger children or as horizontal supranuclear gaze palsy and slowed saccades.…”

The history and accomplishments of the ICGG Gaucher registry

“…Demographics and clinical features in 141 patients with Gaucher disease type 2 and type 3 [42] Effect of imiglucerase on blood, spleen, and liver abnormalities in patients with Gaucher disease type 3 [43] …”

Long-term follow up and sudden unexpected death in Gaucher disease type 3 in Egypt

“…Remarkably, their phenotype was more severe and different from that described for the same genotype in other countries. 13,[17][18][19] It should be noted that 31% of patients in the study analyzing the Neurological Outcomes Subregistry of the International Collaborative Gaucher Group Gaucher Registry as of June 1, 2007, were from Egypt, but their phenotype was not specifically described. 19 Patients with Gaucher disease type 3 in China and Japan seem to have more severe neurologic disease than patients in Europe and the United States.…”