ABSTRACT
Spinocerebellar ataxias (SCAs) constitute a group of autosomal dominant neurodegenerative disorders with no current treatment. The insulin/insulin-like growth factor 1 (IGF-1) system (IIS) has been shown to play a role in the neurological dysfunction of SCAs and other polyglutamine disorders. We aimed to study the biomarker profile of serum IIS components in SCA3. We performed a case-control study with 46 SCA3 patients and 42 healthy individuals evaluating the peripheral IIS profile (insulin, IGF-1, IGFBP1 and 3) and the correlation with clinical, molecular, and neuroimaging findings. SCA3 patients presented lower insulin and IGFBP3 levels and higher insulin sensitivity (HOMA2), free IGF-I, and IGFBP1 levels when compared with controls. IGFBP-1 levels were directly associated with CAG expanded repeat length; IGF-1 was associated with the volumetries of specific brainstem regions on magnetic resonance imaging (MRI). Insulin levels and sensitivity were related to age at onset of symptoms. Our findings indicate an involvement of IIS components in SCA3 neurobiology and IGFBP-1 as a potential biomarker of the disease.
Subject(s)
Insulin-Like Growth Factor Binding Protein 1/blood , Insulin-Like Growth Factor Binding Proteins/blood , Insulin-Like Growth Factor I/metabolism , Insulin/blood , Machado-Joseph Disease/blood , Adult , Ataxin-3 , Case-Control Studies , Female , Humans , Insulin-Like Growth Factor Binding Protein 3 , Machado-Joseph Disease/genetics , Male , Middle Aged , Nerve Tissue Proteins/genetics , Nuclear Proteins/genetics , Repressor Proteins/geneticsABSTRACT
UNLABELLED: X-linked adenoleukodystrophy is a genetic disease that affects the degradation of very long-chain fatty acids. In male patients, common pictures are the cerebral form (CALD), myeloneuropathy (AMN), and Addison-only. OBJECTIVE: To describe the clinical course of affected male patients from South Brazil between 1993 and 2007. METHODS: Affected male patients and their maternal lineages were studied from a clinical, neurological and biochemical standpoint. RESULTS: Eighty-three male patients from 30 families were biochemically evaluated: 51 were affected. 27/51 (54%) presented the cerebral form; 11/51 had AMN (22%); 5 had Addison-only (10%), and 8 (16%) were asymptomatic. Between 2002 and 2006, the minimal incidence was 1:35,000 males in our State (South Brazil). Forty-three affected individuals were followed for 5.4+/-3.7 years. Of 10 boys detected at early stages, three developed CALD. These three boys and another five CALD at baseline were referred to hematopoietic stem cell transplantation. Seven transplants were carried out, 5 with good clinical evolution after 2.2 years post-transplant. The non-transplanted case was later defined as a stable cerebral form. DISCUSSION: Among the present families, the observed cases were comparable to the 50% expected by Mendelian segregation. Based on the natural history, the number of cases that developed CALD was similar to the expected. Transplants were successful in 70% of cases. The occurrence of a stable cerebral form pointed to an urgent need for better markers of active cerebral disease.