Alteration of Liver Enzymes Is a Feature of the Myh9-Related Disease Syndrome

Background: MYH9-related disease (MYH9-RD) is a rare autosomal dominant genetic syndrome characterized by congenital
thrombocytopenia associated with the risk of developing progressive nephropathy, sensorineural deafness, and presenile
cataract. During the collection of a large case-series of patients with MYH9-RD we noticed several cases with unexplained
elevation of liver enzymes. Our aim was to evaluate if the alteration of liver tests is a feature of the MYH9-RD and to define
its clinical significance.
Methods and Findings: Data concerning liver tests, prospectively recorded in the Italian Registry for MYH9-RD, were
collected and compared with those of three control populations: patients with autoimmune thrombocytopenia, patients
with inherited thrombocytopenias other than MYH9-RD, and the participants to a large epidemiologic survey in an Italian
geographic isolate. Thirty-eight of 75 evaluable MYH9-RD patients (50.7%) showed an elevation of ALT and/or AST, and 17 of
63 (27.0%) an increase of GGT. The increases ranged from 1.960.7 to 2.761.6 fold the upper normal limit. The prevalence of
liver test alterations was significantly higher in MYH9-RD patients than in each of the control populations, with odds ratios
ranging from 8.2 (95% CIs 2.2-44.8) to 24.7 (14.8-40.8). Clinical follow-up and more detailed liver studies of a subset of
patients, including ultrasound liver scan, liver elastography and liver biopsy in one case, did not show any significant
structural damage or evolution towards liver insufficiency.
Conclusions: Elevation of liver enzymes is a frequent and previously unrecognized feature of the MYH9-RD syndrome;
however, this defect does not appear to have poor prognostic value.