Autosomal recessive cerebellar ataxia 2 (ARCA2) is a recently identified recessive ataxia due to ubiquinone deficiency and biallelic mutations in the ADCK3 gene. The phenotype of the twenty-one patients reported worldwide varies greatly. Thus, it is difficult to decide which ataxic patients are good candidates for ADCK3 screening without evidence of ubiquinone deficiency. We report here the clinical and molecular data of 10 newly diagnosed patients from seven families and update the disease history of four additional patients reported in previous articles to delineate the clinical spectrum of ARCA2 phenotype and to provide a guide to the molecular diagnosis. First signs occurred before adulthood in all 14 patients. Cerebellar atrophy appeared in all instances. The progressivity and severity of ataxia varied greatly, but no patients had the typical inexorable ataxic course that characterizes other childhood-onset recessive ataxias. The ataxia was frequently associated with other neurological signs. Importantly, stroke-like episodes contributed to significant deterioration of the neurological status in two patients. Ubidecarenone therapy markedly improved the movement disorders, including ataxia, in two other patients. The 7 novel ADCK3 mutations found in the 10 new patients were two missense and five truncating mutations. There was no apparent correlation between the genotype and the phenotype. Our series reveals that the clinical spectrum of ARCA2 encompasses a range of ataxic phenotypes. On one end, it may manifest as a pure ataxia with very slow progressivity and, on the other end, as a severe infantile encephalopathy with cerebellar atrophy. The phenotype of most patients, however, lies in between. It is characterized by a very slowly progressive or apparently stable ataxia associated with other signs of central nervous system involvement. We suggest undergoing the molecular analysis of ADCK3 in patients with this phenotype and in those with cerebellar atrophy and a stroke-like episode. The diagnosis of patients with a severe ARCA2 phenotype may also be performed on the basis of biological data, i.e. low ubiquinone level or functional evidence of ubiquinone deficiency. This diagnosis is crucial since the neurological status of some patients may be improved by ubiquinone therapy.

ObjectivePeripheral ulcerative keratitis (PUK) is a rare but severe ocular complication of rheumatoid arthritis (RA). It can be considered as an ocular manifestation of rheumatoid vasculitis (RV). Our case series aimed to evaluate the efficacy of rituximab (RTX) for PUK occurring in patients with RA.MethodsStudy population were patients with RA-associated PUK treated with RTX 1000 mg on days 1 and 15 at least once after the diagnosis. We identified patients referred to the rheumatology and ophthalmology departments of our hospital between February 2014 and June 2020. We also included patients referred by their specialist after being contacted through the Club Rhumatismes et Inflammation. Demographic data and clinical and biological features were retrospectively collected.ResultsWe included seven patients (three men and four women, median age 58 years). All but one had a long-standing RA with a median disease duration of 13.9 years (IQR 0–30.2). RA was erosive in six out of seven patients. All patients had rheumatoid factors and anticitrullinated peptides antibodies were positive in six of them. PUK was complicated by corneal perforation in three patients and required surgery. After a median follow-up of 29.8 months (IQR 5–75), corneal inflammation was controlled in all patients. PUK recurred in one patient, 8 months after a single infusion of RTX. 71% of the patients presented a good articular response. No patient developed other manifestations of RV. No serious adverse event related to RTX was observed.ConclusionRTX appears to be an efficient and safe therapeutic option in the treatment of RA-associated PUK.

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