Abstract
Wieacker-Wolff syndrome (WRWF) is an X-linked genetic disorder characterized by neuromusculoskeletal abnormalities caused by loss-of-function variants of the ZC4H2 gene. Here, we report the case of a male infant with WRWF manifesting as multiple joint contractures and congenital anomalies at birth. He underwent gastrostomy to treat the gastroesophageal reflux disease, which caused mixed apnea and transient bradycardia. The patient subsequently developed hyperinsulinemic hypoglycemia (HH) and was diagnosed with dumping syndrome. Although he underwent multiple treatments, including alpha-glucosidase inhibitors (α-GI) administration, he continued to exhibit HH with seizures and loss of consciousness. Whole-exome sequencing revealed a novel missense variant of ZC4H2 [NM_018684.4: c.557T>G, p.(Met186Arg)] at Xq11.2 in both the patient and his mother. Based on these results and clinical symptoms, the patient was diagnosed with WRWF. Although WRWF is not considered a major cause of HH, we regarded it as a related complication based on previous reports. Diazoxide treatment was initiated, and the hypoglycemic attacks resolved almost entirely without any notable side effects after 18 mo. To the best of our knowledge, this is the first report of WRWF-associated HH treated with low-dose diazoxide and α-GI. Therefore, diazoxide is recommended for the treatment of WRWF-associated HH.