Table 3.
Systemic clues in the diagnosis of adult-onset leukodystrophies.
| Skin | |
|---|---|
| Alopecia Skin rash Ichthyosis Pigmentation |
CARASIL, Biotinidase deficiency, AMN Biotinidase deficiency Refsum disease, Sjogren-Larsson syndrome X-ALD, AMN |
| Progeroid features | CRMCC, Cockayne syndrome |
| Eyes | |
| Cataract | CTX, mitochondrial disorders, hypomyelinating leukodystrophies, COL4A1-related disorders |
| Axenfeld-Rieger anomaly | COL4A1-related disorders |
| Retinal arterial torturosity/exudates | COL4A1-related disorders, CRMCC |
| Dental | |
| Hypodontia, oligodontia | POLR3-related hypomyelinating leukodystrophy |
| Cardiac involvement | |
| Cardiomyopathy | APBD, Fabry disease, AARS2-related leukoencephalopathy |
| Conduction disturbances Premature atherosclerosis |
Fabry disease CTX |
| Endocrine | |
| Hypogonadism | Gordon Holmes syndrome, POLR3-related hypomyelinating leukodystrophy, AMN, VWMD, AARS2-related leukodystrophy, FXTAS, CLCN2-related leukoencephalopathy |
| Premature ovarian insufficiency | Galactosemia, FXTAS, VWMD, AARS2-related leukoencephalopathy |
| Addison disease | X-ALD, AMN |
| Growth hormone deficiency | POL3-related hypomyelinating leukodystrophy |
| Gastrointestinal involvement | |
| Cholecystitis, gall bladder polyps | MLD |
| Dysmotility Malabsorption GI bleeding |
MNGIE CTX CRMCC |
| Liver involvement | AMACRD, CTX, APBD, CRMCC |
| Skeletal involvement | |
| Bone cysts Osteoporosis |
PLOSL CTX |
| Tendon xanthomas | CTX |
| Respiratory insufficiency | CTX |
| Renal involvement | COL4A1 -related disorders |
| Spondylosis deformans | CARASIL |
AMACR deficiency, α-methyl-acyl-CoA-racemase deficiency; APBD, adult polyglucosan body disease; AMN, adrenomyeloneuropathy; CARASIL, cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy; CRMCC, cerebro-retinal microangiopathy with calcifications and cysts; CTX, cerebrotendinous xanthomatosis; FXTAS, fragile X-associated tremor ataxia syndrome; MLD, metachromatic leukodystrophy; MNGIE, mitochondrial neuro gastro intestinal encephalomyopathy; PLOSL, Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy; VWMD, vanishing white matter disease; X-ALD, X linked adrenoleukodystrophy.