Myotonic dystrophy type 2 and autoimmune chronic gastritis: an incidental association?

Abstract

Myotonic dystrophy type 2 (DM2) is an autosomal dominant multisystem disease caused by a large expansion of a CCTG repeat located in intron 1 of the zinc finger protein 9 (ZNF9) gene on the chromosome 3q21.3. The clinical picture of DM2 shows similarities to as well as differences from myotonic dystrophy type 1 (DM1). DM2 is mainly characterized by myotonia, muscle dysfunction including weakness, myalgia and stiffness, cataracts, cardiac arrhythmia and endocrine disturbances [1]. A recent study found a significantly higher frequency of autoimmune disease and autoantibodies in DM2 patients compared with DM1 subjects and the general population, suggesting a strong association between DM2 and autoimmunity [2]. A 48-year-old Italian woman was recently referred to us with a 4 year history of fluctuating muscle weakness, pain and stiffness of lower limbs. Her past history revealed chronic immune thrombocytopenia (ITP), Hashimoto’s thyroiditis (HT) and mammary cancer. Family history disclosed cardiopathy, myalgias and stiffness in the paternal members. No history of autoimmune disorders was referred in the family members. On admission, neurological examination showed grip myotonia, slight weakness (MRC grade 4) of neck flexors and proximal lower limbs muscles. Routine blood analysis confirmed thrombocytopenia and uncovered mild hyperCKemia (265 U/L; normal 10–170 U/L). Electromyography showed myotonic discharges in both the proximal and distal muscles of the upper and lower limbs. Ophthalmological evaluation revealed initial cataracts. Electrocardiographic and echocardiographic examination excluded conduction abnormalities and cardiomyopathy, respectively. Molecular analysis of dystrophia myotonica protein kinase (DMPK) gene did not reveal CTG repeat expansion. Muscle biopsy (vastus lateralis) showed fiber size variability, increased internal nuclei, frequent nuclear clumps and the evidence of type 2 fiber atrophy. Fluorescence in situ hybridization using (CAGG)5 probe was performed on skeletal muscle sections: the presence of nuclear accumulation of CCUG-containing RNA confirmed the clinical diagnosis of DM2. Serum autoantibody assessment showed the elevated levels of anti-thyroglobulin and antithyroperoxidase antibodies and uncovered high titers of antiparietal cell antibodies (82.8 U/mL; normal \10 U/mL). Thus, we performed esophagogastroduodenoscopy and gastric biopsies which revealed chronic gastritis with intestinal metaplasia, mild gastric atrophy and foveolar hyperplasia, primarily affecting the body/fundus of the stomach. Moreover, further biochemical analysis showed hypergastrinemia (345 pg/mL; normal \108 pg/mL) and vitamin B12 deficiency (103 pg/mL; normal 140–900 pg/mL). However, both anemia and gastrointestinal symptoms were absent. On the basis of laboratory and histopathological findings, a diagnosis of subclinical autoimmune chronic gastritis (ACG) was established. Our case report expands the spectrum of autoimmune disorders in DM2 and further suggests a strong association F. Sicurelli (&) A. Mignarri A. Carluccio D. Marino A. Federico M. T. Dotti Neurology and Neurometabolic Unit, Department of Neurological, Neurosurgical and Behavioural Sciences, University of Siena, Viale Bracci 2, 53100 Siena, Italy e-mail: francesco.sicurelli@gmail.com