Table 2.

Clinical findings as a diagnostic clue for disorders with CNS WMAs

Clinical feature	Disorders
Macrocephaly	Alexander disease, Canavan disease, Megalencephalic leukoencephalopathy with subcortical cysts, 1,2-hydroxy glutaric aciduria, GM2 gangliosidosis
Coarse facies	Sialic acid storage disease, Fucosidosis, Multiple sulfatase deficiency, Mucopolysaccharidosis
Progeroid appearance	Cockayne syndrome
Enamel hypoplasia and other enamel defects	Oculodentodigital dysplasia, Peroxisomal disorders
Oligodontia, hypodontia, delayed eruption, altered sequence of eruption, abnormal colour /shape	POLR3 related disorders (not universal and highly variable) Oculo-dentodigital dysplasia
Propensity for cavities	Cockayne syndrome
Cataract	At birth Hypomyelination with congenital cataract, Childhood ataxia with central nervous system hypomyelination (only connatal cases), Peroxisomal disorders Childhood onset Cerebrotendinous xanthomatosis, POLR3 related disorders
Cherry red spot	Sialidosis, GM2 gangliosidosis, Metachromatic leukodystrophy (some cases)
Glaucoma	Aicardi–Goutières Syndrome, Oculodentodigital dysplasia
Optic atrophy	Metachromatic leukodystrophy, Canavan disease Childhood ataxia with central nervous system hypomyelination, Cerebrotendinous xanthomatosis, Peroxisomal disorders (+/−), POLR3 related disorders (+/−), Hypomyelinating leukodystrophies, Mitochondrial disorders, Oculodentodigital dysplasia
Retinitis pigmentosa	Refsum disease (adolescent and adult onset), Peroxisomal disorders
Vascular retinal defects	Cerebroretinal microangiopathy with calcifications and cysts (Coats plus syndrome)
Angiokeratoma corporis diffusum	Fucosidosis
Ichthyosis	Congenital Sjogren-Larsson syndrome, Ichthyotic keratoderma, spasticity, hypomyelination, and dysmorphic facies Childhood onset Multiple sulfatase deficiency, Sialic acid storage disorder, Peroxisome biogenesis disorders including neonatal Zelleweger syndrome Adrenoleukodystrophy and Infantile Refsum disease Adulthood onset Refsum disease
Hyperpigmentation	X-Adrenoleukodystrophy, Mitochondrial neurogastrointestinal encephalopathy
Xanthomas	Cerebrotendinous xanthomatosis
Photosensitivity	Cockayne syndrome, Tay syndrome
Adrenal insufficiency	X-linked Adrenoleukodystrophy, Peroxisome biogenesis disorders
Hypothyroidism	POLR3 related disorders, Aicardi–Goutières Syndrome, Cerebrotendinous xanthomatosis, Peroxisomal biogenesis disorders
Hypogonadotropic hypogonadism	POLR3 related disorders
Growth Hormone deficiency	POLR3 related disorders, Aicardi–Goutières Syndrome
Ovarian dysgenesis (Premature ovarian failure)	Ovarioleukodystrophy, AARS2-related leukoencephalopathy Peroxisome biogenesis disorders
Hepatosplenomegaly	Multiple sulfatase deficiency, Galactosialidosis, Sialic acid storage disorders
Hepatic dysfunction	Peroxisomal disorders, Aicardi–Goutières Syndrome, Mitochondriopathies Fucosidosis, Sialic acid storage disorders
Chondrodysplasia punctata	Peroxisomal disorders
Dysostosis multiplex	Multiple sulfatase deficiency, Sialidosis