AR-LAD is described as a leukodystrophy with ataxia and sensorineural deafness that includes fibrotic cardiomyopathy and hepatopathy as associated features (Sferra, et al, 2021, pubmed:33964137; FBrf0252013).

Leukodystrophies are a heterogeneous group of rare inherited disorders that mostly involve the white matter of the CNS. These conditions are characterized by primary glial cell and myelin sheath pathology of variable aetiology, which causes secondary axonal degeneration, generally emerging with disease progression. (FBrf0252013 and references cited therein).

Hypomyelinating leukodystrophy 23 with ataxia, deafness, liver dysfunction, and dilated cardiomyopathy (HLD23) is an autosomal recessive neurodegenerative disorder with systemic manifestations. Affected individuals show delayed motor development and ataxic gait in early childhood that progresses to spastic paraplegia with loss of ambulation in the first decades of life. Additional features include progressive sensorineural hearing loss resulting in deafness, hepatic dysfunction with elevated liver enzymes, and dilated cardiomyopathy that ultimately results in death in the first or second decades. (summary by Sferra et al., 2021; pubmed:33964137).[from MIM:619688; 2022.02.06]

Two homozygous missense variants (p.R363Q and p.R365Q) in the ubiquitin E3 ligase RNF220 as the underlying cause of this syndromic form of leukodystrophy in seven consanguineous families; the disease exhibits autosomal recessive inheritance (Sferra, et al, 2021, pubmed:33964137; FBrf0252013).

Hypomyelinating leukodystrophy 23 with ataxia, deafness, liver dysfunction, and dilated cardiomyopathy (HLD23) is caused by homozygous mutation in the RNF220 gene. [from MIM:619688; 2022.02.06]