Table 2. Summary of HSAN1 causing mutations in the SPT1 and SPT2 subunits of SPT.

LCB subunit	Mutation	Clinical effect	Biochemical effect	Ref.
LCB1	C133W	Sensory neuropathy, ulceromutilations, lancinating pains	Increased activity towards l-alanine (KM 9.6 mM), activity towards l-serine unaffected (KM 0.75 mM for WT, 1.4 mM for mutant)	18, 109 and 111
LCB1	C133Y	Sensory neuropathy, ulceromutilations, lancinating pains	Increased levels of deoxysphingoid bases. Reduced SPT activity	18, 109 and 111
LCB1	C133R	Sensory neuropathy	Increased levels of deoxysphingoid bases. Reduced SPT activity	118
LCB1	V144D	Sensory neuropathy, ulceromutilations, lancinating pains	Decreased SPT activity	90, 109 and 110
LCB1	A310G	Uncertain pathological significance	Unknown	123
LCB1	S331F	Hypotonia, ulcerations, severe growth and mental disability, vocal cord paralysis, gastroesophageal reflux	Increased levels of deoxysphingoid bases. Reduced SPT activity	120–122
LCB1	S331Y	As S133F	Increased levels of deoxysphingoid bases. Reduced SPT activity	120–122
LCB1	A352V	Sensory neuropathy, ulceromutilations, lancinating pains	Reduced SPT activity. Does not lead to increased deoxysphingoid base levels in vitro	120 and 121
LCB1	G387A	Not disease associated	Not disease associated	122
LCB2	A182P	Reduced sensation in the feet, sensory loss and motor weakness	Increased levels of deoxysphingoid bases. Reduced SPT activity. Increased activity vs. alanine	124
LCB2	R183W	Mild late onset progressive distal sensory impairment	Elevated 1-deoxysphingolipid levels. No effect on SPT activity	127
LCB2	V359M	Sensory neuropathy, ulceromutilations	Ambiguity towards amino acid substrate	126
LCB2	G382V	Sensory neuropathy, ulceromutilations	Ambiguity towards amino acid substrate	126
LCB2	S384F	Reduced sensation in feet, shooting pains, ulcerations and motor weakness	Reduced activity to l-serine, increased activity to l-alanine	113
LCB2	I504F	Sensory neuropathy, ulceromutilations, osteomyelitis and anhidrosis	Ambiguity towards amino acid substrate	126