Table 3.

Genes of Interest in the Differential Diagnosis of Gaucher Disease

GeneDisorderKey Feature(s) of Disorder Overlapping w/GDComment / Distinguishing Features
Lysosomal storage disorders 1
PSAP Saposin C deficiency or prosaposin deficiency 2 (OMIM 610539)Affected persons may present w/features characteristic of severe neuropathic GD (i.e., progressive horizontal ophthalmoplegia, pyramidal & cerebellar signs, myoclonic jerks, & generalized seizures) or non-neuronopathic disease.Persons w/saposin C deficiency demonstrate GL1 accumulation & visceromegaly but have normal glucocerebrosidase enzyme activity measured in vitro.
ASAH1 Farber disease (FD) (See ASAH1-Related Disorders.)Hepatosplenomegaly (in type 4 FD [neonatal-visceral FD]), hydrops fetalisThe following features are not found in persons w/GD & should direct further investigations to these alternative diagnoses:
  • Coarse facial features
  • Dysostosis multiplex on skeletal radiographs
  • Vacuolated lymphocytes on peripheral blood smear
  • Presence of a cherry-red spot on fundoscopy
  • White matter changes (leukodystrophy) on brain MRI
CTSA Galactosialidosis (OMIM 256540)Hepatosplenomegaly, hydrops fetalis
GALNS MPS IV (See MPS IVA.)Hepatomegaly, hydrops fetalis
GLB1 GM1 gangliosidosis (See GLB1-Related Disorders.)Hepatosplenomegaly, hydrops fetalis
GUSB MPS VII
IDS MPS II Hepatosplenomegaly
IDUA MPS I
LIPA Wolman disease (See Lysosomal Acid Lipase Deficiency.)Hepatosplenomegaly, hydrops fetalis
MAN2B1 Alpha-mannosidosis Hepatosplenomegaly
NEU1 Sialidosis types I & II (OMIM 256550)Hepatosplenomegaly, hydrops fetalis, myoclonic seizures
NPC1
NPC2 		Niemann-Pick disease type C Hepatosplenomegaly, hydrops fetalis
SLC17A5 Infantile free sialic acid storage disease
SMPD1 Niemann-Pick disease types A & B (See Acid Sphingomyelinase Deficiency.)Hepatosplenomegaly
GNPTAB Mucolipidosis II (See GNPTAB-Related Disorders.)Hydrops fetalisCoarse facial features evident at birth, gingival hyperplasia
FUCA1 Fucosidosis (OMIM 230000)Myoclonic seizuresAngiokeratomas
HEXA HEXA disorders Cherry-red spot on eye exam
NAGA Schindler disease (OMIM 609241)

GD = Gaucher disease; GL1 = glucosylceramide; MPS = mucopolysaccharidoses

1.

Lysosomal storage disorders are typically inherited in an autosomal recessive manner. An exception is mucopolysaccharidosis type II, which is inherited in an X-linked manner.

2.

Saposin C is a cofactor for glucocerebrosidase in the hydrolysis of GL1.

From: Gaucher Disease

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