A rare variant (p.G991A) identified in a patient with ketotic hypoglycemia.

We describe the case of a 4-year-old boy who suffered from frequent ketotic hypoglycemia (KH) but did not have hepatomegaly or elevated liver enzyme levels. However, the patient was found to have a rare variant in the gene. To detect the underlying disease in this case, we performed a gene panel analysis covering 59 genes that are involved in fatty acid oxidation, ketone body metabolism and transport, and glycogen storage diseases. We found no reported disease-causing mutations. However, the p.G991A variant in was detected. The allele frequency of this variant is 4.57 × 10 in the population worldwide, but in Japan it is 5.15 × 10. We suspect that this variant may be a major cause of KH in Japanese patients. We performed an enzyme assay on blood cells from the patient. Although the activity of the current PhK variant was not low, it did exhibit thermal instability and a lower affinity to phosphorylase than the wild type. The patient needed bedtime uncooked cornstarch supplementation from age 5 years until he was 9 years old. The patient's condition improved spontaneously without neurological complications. The clinical course and prognosis in this case are similar to those of glycogen storage disease type IXa, which is also caused by an abnormality of .