Table 1.

Late-Onset Inborn Errors of Metabolism or White-Matter Degenerative Diseases.

Disease	Enzyme	Clinical Syndrome	Findings on MRI
Metachromatic leukodystrophy	Arylsulfatase	Causes psychiatric symptoms progressing to dementia	Frontal changes
Adrenoleukodystrophy	ABCD1 peroxisomal membrane transporter protein	X-linked; occurs in young boys and heterozygotic women; symptoms are variable	Posterior changes (variable in women)
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy	Notch 3	Causes stroke, headache, neuropsychiatric symptoms, and dementia	Frontotemporal and white-matter changes
Nasu–Hakola disease	TREM2 (recessive); DAP12	Causes psychiatric symptoms progressing to dementia; also causes bone cysts	Frontal atrophy and white-matter changes
Adult polyglucosan body disorder	Glycogen branching enzyme 1	Causes neuropathy, incontinence, and dementia	Frontotemporal and white-matter changes
Neuronal ceroid lipofuscinosis	CLN1–8 and PPT1; progranulin (recessive)	Causes manic symptoms progressing to dementia, retinopathy, seizures, and granular osmiophilic deposits in white cells, skin, and neurons	Atrophy and white-matter changes
Gaucher’s disease	Glucocerebrosidase	Causes dementia, vertical gaze, and parkinsonism; affects liver, spleen, and bone marrow	Atrophy
Niemann–Pick disease type C	NPC1 and NPC2 (transport protein)	Causes schizophrenia-like symptoms, vertical gaze, parkinsonism, and cerebellar ataxia; affects liver and spleen	Atrophy
Adult Tay–Sachs disease	Hexosaminidase A	Causes manic symptoms, schizophrenia, dementia, amyotrophic lateral sclerosis, and retinal abnormalities	Atrophy and white-matter changes