Clinical and Genetic Analysis of Adrenoleukodystrophy in Adults / 罕见病研究

ABSTRACT

  Objective  Adrenoleukodystrophy (ALD) is the most common peroxisomal diseases with high clinical and genetic heterogeneity. Our study is to analyze the phenotype and genotype characteristics of adult patients with ALD.  Methods  A total of 18 adult patients with ALD admitted to Beijing Tiantan Hospital from May 2016 to April 2021 were recruited, and their clinical manifestations, imaging features, and genetic results were comprehensively analyzed.  Results  Among 18 patients, 6(33%) patients were diagnosed as adrenomyeloneuropathy (AMN), 2(11%) were cerebral AMN, 5(28%) were adult cerebral ALD (ACALD), 2(11%) were childhood cerebral ALD (CCALD), 1(6%) were adolescent cerebral ALD (AdolALD), and 2(11%) were cerebellar variant of ALD. AMN patients presented with adult-onset stiffness and weakness of lower limbs as the initial and main symptoms, and can developed additional cerebral demyelination; In the case of cerebral ALD, ACALD is more common than CCALD and AdolALD. The prominent manifestations were psychiatric disorders, cognitive, and motor impairment. The imaging features were predominantly occipitoparietal involvement or predominantly frontal involvement with or without contrast enhancement marginal to the demyelinated areas; cerebellar ataxia is the main manifestation in patients with cerebellar variant, and the imaging feature was symmetrical involvement of the cerebellar dentate nucleus. Genetically, the most common mutation type was missense mutation (10/18, 55.6%), followed by frameshift mutation (7/18, 38.9%), and splice site mutation (1/18, 5.6%). Moreover, we found five novo mutations, all of which were frameshift mutations.  Conclusions  AMN is the most common subtype of adult patients with ALD. ACALD is common among the cerebral ALD. The proportion of cerebellar variant might have been underestimated.