Clinical and genetic characteristics of Gaucher disease according to phenotypic subgroups

Abstract

PurposeGaucher disease is caused by a β-glucocerebrosidase (GBA) deficiency. The aim of this study is to investigate the clinical and genetic characteristics according to subtypes of Gaucher disease in the Korean population.MethodsClinical findings at diagnosis, GBA mutations, and clinical courses were reviewed in 20 patients diagnosed with Gaucher disease.ResultsEleven patients were diagnosed with non-neuronopathic type, 2 with acute neuronopathic type, and 7 with chronic neuronopathic type. Most patients presented with hepatosplenomegaly, thrombocytopenia, and short stature. In the neuronopathic group, variable neurological features, such as seizure, tremor, gaze palsy, and hypotonia, were noted at age 8.7±4.3 years. B cell lymphoma, protein-losing enteropathy, and hydrops fetalis were the atypical manifestations. Biomarkers, including chitotriosidase, acid phosphatase, and angiotensin-converting enzyme, increased at the initial evaluation and subsequently decreased with enzyme replacement treatment (ERT). The clinical findings, including hepatosplenomegaly, thrombocytopenia, and skeletal findings, improved following ERT, except for the neurological manifestations. L444P was the most common mutation in our cohort. One novel mutation, R277C, was found.ConclusionAlthough the clinical outcome for Gaucher disease improved remarkably following ERT, the outcome differed according to subtype. Considering the high proportion of the neuronopathic form in the Korean population, new therapeutic strategies targeting the central nervous system are needed, with the development of a new scoring system and biomarkers representing clinical courses in a more comprehensive manner.

Differential effects of severe vs mild GBA mutations on Parkinson disease

“…23 The p.I260T mutation (described in a patient with PD in reference 12) is now classified as severe based on a report of a patient with type II GD with this mutation, 26 the p.S271G mutation (described in a patient with PD in reference 2) is now classified as mild based on a report of a patient with type I GD with this mutation, 27 and the p.R277C mutation (described in a patient with PD in reference 2) is now classified as mild based on a report of a patient with type I GD with this mutation. 28 The classification of all the mutations is detailed in table e-1 on the Neurology ® Web site at Neurology.org.…”

The GBA p.G85E mutation in Korean patients with non-neuronopathic Gaucher disease: founder and neuroprotective effects

“…GD patients harbouring a p.N409S mutation even in one allele can be excluded from a diagnosis of neuronopathic GD (type 2 or 3) [3], suggesting that the mutation may exert a neuroprotective effect [3,[5][6][7]. However, the p.N409S mutation has been rarely identi ed among Asian GD patients, particularly among Japanese and Korean patients [4,7,8]. Instead, p.L483P and p.F252I mutations are more prevalent among Asian groups, where the homozygosity of these mutations is generally associated with neuronopathic GD [4,[8][9][10]].…”

“…However, the p.N409S mutation has been rarely identi ed among Asian GD patients, particularly among Japanese and Korean patients [4,7,8]. Instead, p.L483P and p.F252I mutations are more prevalent among Asian groups, where the homozygosity of these mutations is generally associated with neuronopathic GD [4,[8][9][10]].…”

“…The GBA p.G85E mutation has been identi ed in Asian populations, exclusively in Korea, China, and India [4,[8][9][10]15]. Furthermore, the p.G85E mutation was found exclusively in non-neuronopathic GD patients [4,8], suggesting a potential neuroprotective allele. This study aimed to investigate the clinical characteristics of GD patients carrying p.G85E mutation and mutation spectrum of GBA among Korean GD patients and to test for a founder effect for the GBA p.G85E mutation via haplotype analysis.…”

Substrate reduction therapy in three patients with Gaucher disease

“…There are three subtypes of GD, characterized by the presence of neurologic symptoms, age at identification, and disease progression rate: non-neuronopathic GD (type 1), acute neuronopathic GD (type 2), and chronic neuronopathic GD (type 3) [4].…”