Table 2.

Treatable IEM That Resemble HSP

Inborn error of metabolism	Gene / Inheritance	Clinical manifestations	Treatment
Adrenoleukodystrophy (OMIM #300100)	ABCD1 / X-linked	Childhood cerebral form: Progressive spasticity, cognitive decline, behavioral dysregulation, vision impairment, seizures, adrenal insufficiency	Allogeneic HSCT [95, 96] Ex-vivo gene therapy [77]
Arginase 1 deficiency (OMIM #207800)	ARG1 / autosomal-recessive	Spasticity (progressing from a spastic diplegia to tetraplegia), DD/ID, seizures	Protein restriction [63] Pegzilarginase [97]
Biotinidase deficiency (OMIM #253260)	BTD	Spasticity, developmental delay / intellectual disability, seizures, ataxia, vision impairment, hearing loss, cutaneous abnormalities	Biotin [64]
Cerebrotendinous xanthomatosis (OMIM #213700)	CYP27A1 / autosomal-recessive	Spasticity, ataxia, parkinsonism, cognitive impairment, seizures, peripheral neuropathy, tendon xanthomas, neonatal jaundice, bilateral childhood-onset cataracts, childhood-onset chronic diarrhea	Supplementation with chenodeoxycholic acid [68]
Dopa-responsive dystonia (OMIM #128230)	GCH1 / autosomal-dominant	Dystonia (often involving limbs first, often with diurnal fluctuation, responsive to levodopa), parkinsonism, spasticity	Levodopa/carbidopa [79]
Hyperornithinemia-hyperammonemia–homocitrullinuria (HHH) syndrome (OMIM #238970)	SLC25A15 / autosomal-recessive	Progressive spasticity with pyramidal signs, cognitive impairment, cerebellar signs, epilepsy.	Protein restriction, citrulline and arginine supplementation [63]