OMIM ID:
Adrenoleukodystrophy, Autosomal
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
This early onset and rapidly progressive form of adrenoleukodystrophy is rare. The early onset and rapidly fatal course of the disease has limited full delineation of the ocular features. The most striking is the presence of ‘leopard-spots’ pigmentary changes in the retina. Polar cataracts, strabismus, and epicanthal folds have also been reported.
Systemic Features
Onset of symptoms occurs shortly after birth often with seizures and evidence of psychomotor deficits. Rapid neurologic deterioration begins at about 1 year of age with death usually by the age of 3 years. Hyperpigmentation of the skin may be apparent a few months after birth. Opisthotonus has been observed. The ears may be low-set, the palate is highly arched, and the nostrils anteverted. Frontal bossing may be present. Serum pipecolic acid and very-long-chain fatty acids (VLCFAs) can be markedly elevated. Cystic changes in the kidneys have been reported.
Genetics
Inheritance
This is an autosomal recessive peroxismal disorder resulting from homozygous mutations in receptor gene mutations such as PEX1, PEX5, PEX13, and PEX26.
There is also an X-linked recessive adrenoleukodystrophy (300100) sometimes called ALD but it lacks some of the morphologic features and is somewhat less aggressive.
Neonatal adrenoleukodystrophy along with infantile Refsum disease (266510, 601539) and Zellweger syndrome (214100) are now classified as Zellweger spectrum or perioxismal biogenesis disorders.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.