Abstract
Cases A 47-year-old Turkish man presented with six months of cognitive decline and gait disturbance. He had global dysphasia, upper motor neuron signs and ideomotor apraxia. MRI demonstrated extensive periventricular and subcortical left parietal and temporo-occipital white matter abnormalities. Bloods showed elevated very long-chain fatty acids (VLCFAs). X-linked adrenoleukodystrophy was diagnosed with genetic testing pathogenic for ABCD1 gene variant. He deteriorated and passed away six months later.
A 27-year-old Indigenous woman had progressive gait abnormalities and falls since late teens. She had whispering dystonia, spastic and scissoring gait, bilateral Wartenberg’s sign, lower limb upper motor neuron signs, proximal lower limb weakness and right foot drop. Neuromuscular gene panel revealed TUBB4A gene positivity.
Background Adult-onset leukodystrophies are rare genetic disorders primarily affecting myelin development. It is categorized into hypomyelinating (eg. TUBB4A mutation) and demyelinating leukodystrophies (eg. X-linked adrenoleukodystrophy). Clinical presentation is often insidious and variable although generally includes motor deficits and cognitive decline. TUBB4A-related hypomyelinating leukodystrophy presents with childhood-onset delayed motor development, dystonias, spastic tetraplegia, ataxia with basal ganglia and cerebellar atrophy. X-linked adrenoleukodystrophy presents with altered behaviour, apraxia, astereognosis, ataxia and seizures. Extraneurological signs vary per adrenoleukodystrophy subtype including endocrine, ophthalmological or cutaneous disorders. MRI pattern of white matter involvement guides disease subtype diagnosis. Targeted testing (eg. VLCFAs) is supportive and genetic testing provides diagnosis. Whilst there is no cure, early recognition of diagnosis is encouraged to facilitate appropriate supportive measures. Bone marrow transplantation has been beneficial in children with adrenoleukodystrophy but not universally useful in all forms of adrenoleukodystrophy.
