“Background

Hypokalemic Periodic Paralysis (HypoKPP) is a rare autosomal dominant disorder caused by pathogenic variants of 3 genes coding for muscle ion channels, characterized by episodic flaccid paralysis in association with very low blood potassium levels, usually after strenuous exercise or high carbohydrate intake. Patients with elevated creatine kinase (CK), mostly during the paralysis, have been reported; nevertheless, there are anecdotical descriptions of patients with elevated CK between the episodes.

Case Series

We present the data of 10 patients affected by HypoKPP diagnosed trough NGS panels and followed at the Metabolic and Muscular Unit of Meyer Children’s Hospital IRCCS. Among them, 6 patients are heterozygous for the common c.1583G>A variant of CACNA1S gene, one for another pathogenic variant of the same gene, 3 for variants of other genes (2 of SCN4A and one of KCNJ2, respectively).
In 7 cases, the value of CK was elevated in at least one occasion during the disease course (range 223-2145 IU/L); interestingly, in the 4 cases not displaying the common CACNA1S variant, the elevation of CK preceded the genetic diagnosis, even before the onset of paralysis.

Conclusion

In our case series of HypoKPP, elevated CK is a frequent finding; in 4 cases, it allowed the diagnosis even before the appearance of clinical paralysis.
Our data highlights the importance of including the genes responsible for HypoKPP (CACNA1S, SCN4A, and KCNJ2) in gene panels for the work-up of hyperCKemia and rhabdomyolysis.”