Progression rate of myelopathy in X-linked adrenoleukodystrophy heterozygotes.
X-linked adrenoleukodystrophy heterozygote women can present adult onset myeloneuropathy and little is known about its natural history. We aimed to describe the progression rate of the neurological impairment in the prospective follow-up of our cohort and to look for prognostic factors. The neurological scales Japanese Orthopaedic Association (JOA) and Severity Score System for Progressive Myelopathy (SSPROM) were applied at baseline in 29 symptomatic carriers and in follow-up visits. Age at onset, disease duration, X inactivation pattern, determination of the allele expressed, plasma levels of the very long chain fatty acids and of the neuron-specific enolase, and somato-sensory evoked potentials, were taken at baseline. The slope of the linear regression of both JOA and SSPROM versus disease duration since the first symptom was estimated using mixed modeling. JOA and SSPROM decreased 0.42 and 1.87 points per year, respectively (p < 0.001). None of the parameters under study influenced these rates. We estimated that the number of carriers per arm needed in a future 12 month trial with 80% power and a 50% reduction in disease progression would be 225 women for JOA and 750 for SSPROM. The progression rates of the studied neurological scales were small, did not depend on any modifier factor known, and reflected the characteristically slow worsening of symptoms in X-ALD heterozygotes. Better biomarkers are still necessary for future studies.
Post-Graduation Programs in Genetics and Molecular Biology, Porto Alegre, Brazil.
Clarissa Troller
CT
Habekost
Fernanda Santos
FS
Pereira
Carmen Regla
CR
Vargas
Daniella Moura
DM
Coelho
Vitor
V
Torrez
Jean Pierre
JP
Oses
Luis Valmor
LV
Portela
Pedro
P
Schestatsky
Vitor Torres
VT
Felix
Ursula
U
Matte
Vanessa Leotti
VL
Torman
Laura Bannach
LB
Jardim
D000326:Adrenoleukodystrophy / Q000175:diagnosis* / Q000235:genetics*; D000328:Adult; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D013118:Spinal Cord Diseases / Q000175:diagnosis* / Q000235:genetics*; D055815:Young Adult