TABLE 1.
Inborn errors of sphingolipid metabolism
| Disease (GENE) | Enzyme Defect/Lipid Defect | Major Systems Affected | References |
| Disorders of Ceramide Synthesis | |||
| Hereditary sensory neuropathy type 1 (SPTLC1 and SPTLC2) | Serine palmitoyl transferase/ deoxysphingolipids | • Nervous | (6, 10, 11) |
| Progressive symmetric erythrokeratoderma (KDSR) | 3-Keto-dihydrosphingosine reductase/ceramide | • Skin | (12, 13) |
| • Hematologic | |||
| Autosomal recessive congenital ichthyosis (CERS3) | Ceramide synthase 3/ceramide | • Skin | (15, 16) |
| Myoclonic epilepsy (CERS1) | Ceramide synthase 1/ceramide | • Nervous | (17) |
| Progressive leukodystrophy (DEGS1) | Dihydroceramide desaturase/ceramide | • Nervous | (18) |
| Disorders of Glycosphingolipid Synthesis | |||
| Autosomal recessive congenital ichthyosis (UGCG) | UDP-glucose ceramide glucosyltransferase/ glucosylceramide | • Skin | (25) |
| Autosomal recessive infantile-onset symptomatic epilepsy syndrome (ST3GAL5) | GM3 synthase/gangliosides | • Nervous | (26–28) |
| Hereditary spastic paraplegia (B4GALNT1) | GM2 synthase/gangliosides | • Nervous | (29, 30) |
| Disorders of Nonlysosomal Sphingolipid Degradation | |||
| Progressive leukodystrophy (ACER3) | Alkaline ceramidase 3/ceramide | • Nervous | (33) |
| Nephrotic syndrome type 14 (SGPL1) | S1P lyase/S1P, sphingosine, ceramide | • Kidney | (35–37) |
| • Skin | |||
| • Nervous | |||
| • Endocrine | |||
| • Immune | |||
| Sjögren–Larsson syndrome (ALDH3A2) | Fatty aldehyde dehydrogenase/fatty aldehydes | • Nervous | (38) |
| • Skin | |||
| Disorders of Lysosomal Sphingolipid Degradation | |||
| Farber lipogranulomatosis (ASAH1) | Acid ceramidase/ceramide | • Nervous | (39) |
| Fabry disease (GLA) | α-Galactosidase A/ globotriaosylceramide | • Kidney | (39) |
| • Vascular | |||
| • Gastrointestinal | |||
| Gaucher disease: type I, type II, type III, and perinatal lethal form (GBA1) | β Glucocerebrosidase, also known as β-glucosidase/ glucocerebroside, glucosylsphingosine | • Nervous | (39) |
| • Skin | |||
| • Respiratory | |||
| • Hepatic | |||
| • Hematologic | |||
| • Skeletal | |||
| GM1 gangliosidosis: type I, type II, and type III (GLB1) | β-Galactosidase/GM1 ganglioside | • Nervous | (39) |
| • Skeletal | |||
| GM2 gangliosidosis, Tay–Sachs disease (HEXA) | β-Hexosaminidase/GM2 ganglioside | • Nervous | (39) |
| GM2 gangliosidosis, Sandhoff disease (HEXB) | β-Hexosaminidase/GM2 ganglioside, GA2 glycolipid | • Nervous | (39) |
| GM2 gangliosidosis, GM2 activator deficiency (GM2A) | GM2 ganglioside activator/ GM2 ganglioside, glycosphingolipids | • Nervous | (39) |
| Globoid cell leukodystrophy, also known as Krabbe disease (GALC) | Galactosylceramidase/galactocerebroside, psychosine | • Nervous | (39) |
| Metachromatic leukodystrophy (ARSA and PSAP) | Arylsulfatase A and prosaposin/sulfatides | • Nervous | (39) |
| Niemann-Pick disease types A and B (SMPD1) | Sphingomyelin phosphodiesterase/ sphingomyelin | • Nervous | (39) |
| • Hepatic | |||
| • Hematologic | |||
| Disease Predisposition | |||
| Childhood asthma (ORMDL3) | Serine palmitoyl transferase/ sphingolipid levels? | • Respiratory | (21, 23) |
| Ulcerative colitis (ORMDL3) | Serine palmitoyl transferase/ sphingolipid levels? | • Gastrointestinal | (22) |
| Parkinson’s disease (GBA1) | β Glucocerebrosidase, also known as β-glucosidase/ glucocerebroside, glucosylsphingosine | • Nervous | (45–47) |