Paroxysmal Cranial Dyskinesia and Nail-Patella Syndrome Caused by a Novel Variant in the LMX1B Gene.

BACKGROUND: In a Danish family, multiple individuals in five generations present with early-onset paroxysmal cranial dyskinesia, musculoskeletal abnormalities, and kidney dysfunction. OBJECTIVE: To demonstrate linkage and to identify the underlying genetic cause of disease. METHODS: Genome-wide single-nucleotide polymorphisms analysis, Sequence-Tagged-Site marker analyses, exome sequencing, and Sanger sequencing were performed. RESULTS: Linkage analyses identified a candidate locus on chromosome 9. Exome sequencing revealed a novel variant in LMX1B present in all affected individuals, logarithm of the odds (LOD) score of z = 6.54, predicted to be damaging. Nail-patella syndrome (NPS) is caused by pathogenic variants in LMX1B encoding a transcription factor essential to cytoskeletal and kidney growth and dopaminergic and serotonergic network development. NPS is characterized by abnormal musculoskeletal features and kidney dysfunction. Movement disorders have not previously been associated with NPS. CONCLUSIONS: Paroxysmal dyskinesia is a heretofore unrecognized feature of the NPS spectrum. The pathogenic mechanism might relate to aberrant dopaminergic circuits. © 2020 International Parkinson and Movement Disorder Society.

Administration of the same dose of epoetin-beta intravenously and subcutaneously to patients with renal anaemia.

OBJECTIVE: Subcutaneous (s.c.) administration of erythropoietin (EPO) is recommended over the intravenous (i.v.) route to reduce doses and costs. Optimal iron treatment is important for the optimal EPO effect. This study investigated whether the haemoglobin (Hb) level of a single patient could be preserved with the same dose of EPO given i.v. as given s.c. MATERIAL AND METHODS: One-hundred and forty-five haemodialysis patients with the same weekly EPO dose s.c. for 3 months and a stable Hb (maximum fluctuation of 1 mmol/l) were randomized in a crossover study to group A (4 months i.v. then 4 months s.c. EPO) or group B (4 months s.c. then 4 months i.v. EPO, with unchanged EPO dose). Ferritin had to be 300-800 µg/l or transferrin saturation ≥ 20%. Patients with a fall in Hb >1 mmol/l were withdrawn. RESULTS: Ferritin and transferrin saturation remained within the target range, and mean Hb in the range of 1 mmol/l. Mean EPO doses were unchanged in both groups, and no difference was found between the dropouts due to Hb fall >1 mmol/l in the i.v. and s.c. groups during the first period of the trial. CONCLUSION: In iron-replete haemodialysis patients the same EPO dose given intravenously is just as effective as given subcutaneously.