Neurological impairment among heterozygote women for X-linked Adrenoleukodystrophy: a case control study on a clinical, neurophysiological and biochemical characteristics

Orphanet Journal of Rare Diseases

Laura Bannach Jardim⁵  Ursula Matte²  Fernanda dos Santos Pereira⁵  Luis Valmor Portela⁴  Jean Pierre Oses⁸  Vitor Torrez³  Carmen Regla Vargas⁶  Daniella Moura de Coelho⁶  Vitor Felix Torres¹  Pedro Schestatsky¹  Clarissa Troller Habekost⁷ 

[1] Neurology Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil;Laboratory of Gene Therapy, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil;Post-Graduation Program in Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil;Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil;Laboratory of Genetic Identification, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil;Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil;Instituto Nacional de Genética Médica Populacional (INAGEMP), Porto Alegre, Brazil;Instituto Nacional de Ciência e Tecnologia em Excitotoxicidade e Neuroproteção (INCTEN), Porto Alegre, Brazil

关键词: Spastic paraplegia;    X inactivation;    Nerve conduction;    Evoked potentials;    Neuron-specific enolase;    SSPROM;    JOA;    X-ALD carriers;    X-ALD heterozygote females;    X-linked adrenoleukodystrophy;   

Others  :  863313
DOI  :  10.1186/1750-1172-9-6

 received in 2013-12-02, accepted in 2014-01-03,  发布年份 2014

【 摘 要 】

Background

Neurologic impairments in female heterozygotes for X-linked Adrenoleukodystrophy (X-ALD) are poorly understood. Our aims were to describe the neurological and neurophysiological manifestations of a cohort of X-ALD heterozygotes, and to correlate them with age, disease duration, mutations, X-inactivation and serum concentrations of a marker of neuronal damage, neuron-specific enolase (NSE).

Methods

All 45 heterozygotes identified in our region, with previous VLCFA and molecular diagnosis, were invited to be evaluated through myelopathy scales JOA and SSPROM, nerve conduction studies and somatosensory evoked responses. X inactivation pattern was tested by HUMARA methylation assay. Serum NSE was measured by eletrochemiluminescense.

Results

Thirty three heterozygote women were recruited: 29 (87%) were symptomatic. Symptomatic and asymptomatic women presented different m ± sd ages (43.9 ± 10.2 versus 24.3 ± 4.6), JOA (14.5 ± 1.7 versus 16.6 ± 0.2) and SSPROM (86.6 ± 7.9 versus 98.4 ± 1.1) scores (p < 0.05). Both JOA (r = −0.68) and SSPROM (r = −0.65) correlated with age, irrespectively of the disease status (p = 0.0001, Spearman). Delayed latencies in the central ascending conduction studies on the lower limbs were present in 72% of all heterozygotes, and correlated with SSPROM (r = −0.47, p = 0.018, Spearman). NSE values were higher in heterozygote than in control women (12.9 ± 7 and 7.2 ± 7 ng/ml, p = 0.012, Mann-Whitney U). Mutation severity and inactivation patterns were not associated with neurologic status.

Conclusion

Neurologic manifestations, clearly related to age, were quite common in the present cohort. JOA and SSPROM scales were able to discriminate the asymptomatic from the symptomatic heterozygotes. Both scales might be useful tools to follow disease progression, in future studies.

【 授权许可】

   
2014 Habekost et al.; licensee BioMed Central Ltd.

【 图 表 】

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