Gaucher disease was first described in 1882 by a French medical student, Philippe Gaucher, who assumed that the large splenic cells, which today bear his name, were a manifestation of a primary neoplasm of the spleen. More than a century later, Gaucher disease is known as the most prevalent lysosomal storage disorder, caused by an inherited enzymatic defect with consequent accumulation of undegraded glucocerebroside in monocyte-macrophage cells—the ''Gaucher cells.''[1] Nonetheless, neither quantity of residual activity nor genotype can accurately predict the type or degree of severity of the phenotype except in a broad sense. Thus the clinical heterogeneity that marks all forms of Gaucher disease is attributable only in part to the more than 200 mutations within the p-glucocerebrosidase gene;[2] other genetic and/or environmental factors undoubtedly also influence phenotype.

ethnic, it is especially prevalent among Ashkenazi Jews (1:850 live births). There is tremendous heterogeneity in the severity of clinical manifestations, ranging from asymptomatic to severely debilitating disease [often defined by the Zimran Severity Score Index (SSI), which awards up to 30 points based on disease features].

Types II and III, both relatively rare and pan-ethnic, are marked by the involvement of the central nervous system.[3] Horizontal supranuclear gaze palsy is pathognomonic for neuronopathic forms.

Type II, the infantile (acute) form, is characterized by several neurological features, including hypertonic posturing, strabismus, trismus, and retroflexion of the head, in addition to massive organomegaly. The onset of symptoms is usually during the first 6 months of life, with progressive deterioration of neurological function until death, usually before the second year.

Type III Gaucher disease has been further subclassi-fied: type Ilia patients exhibit mild to moderate hepatosplenomegaly and slowly progressive neurological deterioration, frequently associated with recurrent myo-clonic seizures. Patients with type IIIb exhibit massive hepatosplenomegaly, frequently accompanied by lung involvement, but with minimal neurological signs, usually only the horizontal supranuclear gaze palsy.

Although cardiac involvement is rare in all forms, a unique variant, type IIIc, has been described in Japanese, Spanish, and Arab children, all homozygous for the D409H (1342C) mutation, who evince progressive calcification of aortic and/or mitral valves of the heart that is life-threatening.[4] Homozygosity for this mutation is the single instance of relatively tight genotype-phenotype correlation in Gaucher disease.

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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