Phenotype and molecular characterization of Wilson's disease in Morocco.

BACKGROUND AND STUDY AIMS: In Morocco the prevalence of Wilson disease (WD) and the spectrum of mutations are not known. The aim of the present study was to estimate the prevalence of WD in Morocco, to evaluate the phenotype among a large cohort of WD patients, and to characterize ATP7B variants in a subgroup of WD patients. PATIENTS AND METHODS: We collected data from 226 patients admitted to five university hospital centers in Morocco between 2008 and 2020. The diagnosis was based on clinical manifestations, function tests and biochemical parameters. The genotype was characterized in 18 families diagnosed at the University Hospital Center of Marrakesh, by next generation sequencing. RESULTS: The mean annual prevalence in Morocco was 3.88 per 100,000 and the allele frequency was 0.15 %. Among the 226 patients included (121 males and 105 females), 196 were referred for a hepatic or neurological involvement and 30 were asymptomatic. The mean age at diagnosis was 13 ± 5.1 years (range: 5 - 42 years). Consanguinity was found in 63.3 % of patients. The mean duration of illness was 2.8 ± 1.9 years. Kayser-Fleischer rings were found in 131 (67.9 %) of 193 patients. Among the 196 symptomatic patients, 141/159 (88.7 %) had low serum ceruloplasmin (<0.2 g/L) and a high 24-hours urinary copper (>100 µg/day) was found in 173/182 (95.1 %) patients. The initial treatment was D-penicillamine in 207 patients, zinc acetate in five, zinc sulfate in five, and nine patients were not treated; 60/207 (29 %) patients have stopped treatment. A total of 72 patients died; the mortality rate was 31.9 %. Eight different ATP7B variants were identified among the 18 patients studied, of which two were novel (p.Cys1104Arg and p.Gln1277Hisfs*52), and six previously published (p.Gln289Ter, p.Cys305Ter, p.Thr1232Pro, p.Lys1020Arg, p.Glu583ArgfsTer25 and c.51+4A>T). All informative patients were homozygous for the disease-causing mutation. CONCLUSION: In Morocco, a high prevalence due to consanguinity and a high mortality rate due to the difficulty of diagnosis and lack of treatment were observed in WD patients. NGS sequencing identified new ATP7B variants in WD patients from Morocco.

[Macrophage activation syndrome revealing subcutaneous T-cell lymphoma in a 16-year old adolescent]. / Syndrome d'activation macrophagique révélant un lymphome T sous-cutané chez un adolescent de 16 ans.

Macrophage activation syndrome (MAS) is a multisystemic disorder resulting from an over-activation of the immune system leading to a more or less diffuse macrophagic infiltration into the tussues. Clinical signs including fever, hepatosplenomegaly, adenopathy are associated with abnormal values in laboratory test results (bi or pancytopenia, hepatic cytolysis, elevated LDH levels, coagulopathy) and hemophagocytosis. In children, it can be primary or secondary to several disorders. We report the case of a 16-year old patient admitted to the Department of Pediatrics with febrile leukopenia associated with impaired general condition and circular erythematous lesions spread to the lower limbs. The diagnosis of macrophage activation syndrome was retained based on clinical signs, laboratory test results and cytological results. Skin biopsy of these lesions showed subcutaneous panniculitis-like T-cell lymphoma. The purpose of this study is to insists on the peculiarities of this clinical case given the rarity of this type of subcutaneous T-cell lymphoma, much more in this age group. We want to highlight the importance of suspecting subcutaneous T-cell lymphoma in patients with MAS associated with subcutaneous erythematous lesions because this could be life threatening.

Actuality of juvenile dermatomyositis.

Juvenile dermatomyositis is a rare disorder, but remains the most commonly occurring chronic inflammatory myopathy among children. Other than the proximal muscles and skin, which are routinely affected, vasculopathy may affect other viscera and can be multisystemic. A redefinition of the diagnostic criteria is currently underway and is likely to lead to other clinical signs and to sensitive and non-invasive examinations such as MRI. The impact of juvenile dermatomyositis on health and quality of life remains significant despite systemic corticosteroid therapy and immunosuppressor treatment, which have considerably improved the prognosis. Numerous predictors for favourable and pejorative evolution have been identified. The standardisation and the generalisation of clinical assessment tools will make it possible to carry out the clinical trials required to determine the relevance of the new therapeutic options available for children.