Familial gluten ataxia

Autor: Carlos Hernández-Lahoz, Gerard Mauri-Capdevila, Jorge Mier-Juanes, Juan Vega-Villar, Luis Rodrigo-Sáez
Rok vydání: 2013
Předmět:
Zdroj: Movement Disorders. 29:308-310
ISSN: 0885-3185
DOI: 10.1002/mds.25783
Popis: Gluten ataxia (GA) is an autoimmune gluteninduced disease that appears in predisposed subjects. It is characterized by sporadic, progressive cerebellar ataxia, alone or in combination with postural tremor and/or peripheral neuropathy. Among the most characteristic findings is the higher serological prevalence of antigliadin antibodies (AGAs) compared to healthy controls. Deposition of immunoglobulin A (IgA) antibodies against isotype 6 of tissue-transglutaminase (tTG6) has been found around the brain vessels in the cerebellum, pons, and medulla of GA patients. Damage to the cerebellum is mainly related to antibody cross-reactivity between antigenic epitopes on Purkinje cells and T-lymphocyte immune response, activated after exposure to gluten proteins. Cerebellar atrophy on magnetic resonance imaging (MRI) is seen in up to 60% of GA patients. Normally the insidious onset of ataxia occurs in the 6th or 7th decade of life. Patients may have a long history of gastrointestinal symptoms but only one third show evidence of mild enteropathy in duodenal biopsies. The response to treatment with a gluten-free diet (GFD) is favorable, not only with respect to digestive complaints but also to the neurological disease. When the cerebellar neuron degeneration is significant as a consequence of a delayed diagnosis, the neurological manifestations may be considered irreversible. 1–4 We present a family composed of 9 siblings, six of whom were suffering from gait ataxia accompanied by varying degrees of postural hand and cephalic tremor. There was no cognitive impairment in any of the patients, but most were suffering from mild to moderate emotional disturbances. Dysarthria, nystagmus and numbness in the legs and feet were present in three of them. Neurological symptoms, which appeared in all six in adulthood, had slowly progressed over the last 3 to 6 years. The six had a long history of digestive symptoms, the most severe of which was gastroesophageal reflux disease (GERD). Their mother, already deceased, had suffered from both neurological and digestive problems. The clinical characteristics of ataxic patients at the time of diagnosis are listed in Table T1 1. The study was approved by the Hospital Ethics Board. The patients included in this study provided written informed consent for video-filming and duodenal biopsy. All 6 patients were screened for inherited ataxias such as Friedreich ataxia and SCA1, SCA2, SCA3, SCA6, SCA7, SCA12, SCA17, and DRPLA with negative results. Tests for the study of progressive ataxia, including CSF analysis, and paraneoplastic antibodies, were also negative. Immunoglobulin quantification was carried out and IgA deficiency was ruled out in all 6 cases. IgA AGAs were positive in 4 cases and IgA antibodies against isotype 2 of tissue-transglutaminase (tTG2) were negative in all six. MRI revealed mild cerebellar atrophy in only 2 cases, both of whom also showed neurophysiological evidence of mild sensorymotor axonal neuropathy. Duodenal biopsies showed increased intraepithelial lymphocytic infiltration in all 6 patients, with over 25 intraepithelial lymphocytes per 100 epithelial cells and normal villous architecture. Lymphocytic enteritis (LE) may be due to many different etiologies affecting the gut. In all our patients the presence of Helicobacter pylori was excluded by using the urea-C13 breath test. Intestinal parasites (Giardia and others) were absent in duodenal biopsies, as were ova and parasites in stools. There were no data of Crohn disease in any of the patients, and none were taking nonsteroidal antiinflammatory drugs on a long term basis. If all these causes have been ruled out, LE may also be part of gluten-sensitive enteropathy (GSE). It is then classified as Marsh 1 type lesion, the most common finding of duodenal biopsies of celiac disease (CD) in adults with negative serology. The 6 patients with ataxia started on a GFD, and after an average period of 3 months, digestive and neurological benefits were noticeable in all of them. -----------------------------------------------------------Funding agencies: None.
Databáze: OpenAIRE
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