GSD IXc is caused by PHKG2 mutation, which is rare in the population (2/277190) (8).we present this rare condition that will be considered the first confirmed case of GSD IX reported in Syria. that parental consanguinity has a high rate in SYR (30–40%) (18) and hereditary metabolic diseases rate remained unknown and under estimated because of the lake of enzymatic and genetic essay in our country. On the other hand, consanguinity is a deep-rooted tradition in Syria especially the Especially in some region as the Daraa countryside which the family is originated and under developed area .
The PHKG2 mutation has a wide clinical manifestations (6). Hepatomegaly and growth retardation represent the most important symptoms(6) .Some patients develop splenomegaly ,a delay of growth and motor development, ascites ,failure to thrive comparing with their peers. fatigue (6). Jaundice, doll face, protuberant abdomen and mild hepatic dysfunction are common between patients with GSDs (11). Neuromuscular symptoms can be also seen especially hypoglycemic seizures, generalized muscular hypotonia, and weakness (12, 13).
Laboratory tests are unhelpful because the changes are unspecific and interfere with other hepatic and muscle types (13). Tests reveal fasting hypoglycemia, hepatic enzyme elevation, high serum transaminase, ketosis, cholestasis, increased Plasma cholesterol, triglycerides and total lipids with pathologic glucagon tolerance test (14, 11, 8, 15). Normal uric acid levels, CPK and a slight elevation of plasma aminotransferases usually distinguish type IX from GSD type III (12, 17 ). Lactic acidosis is less common in type IX unlike GSD type I (12, 17).
Ultrasonography shows the increase in liver size, periportal and parenchymal echogenicity, Cholestasis and the flow in hepatic vessels (13, 12). The architecture of liver lobes often maintains normality as fibrosis and cirrhosis are less likely to happen in contrast with GSD III.
Endoscopic ultrasound may reveal esophageal varices (8). The erythrocytes and Leukocytes test can be helpful to detect PhK activity but it may be normal in some cases (16, 11).
Liver biopsy guides us to GSD IX because it detects glycogen particle accumulation glycogenosis ) with peripheral cell organelles, decreased activity of PHK enzyme ,a lack of hepatic activated phosphorylase and fibrosis (15). In muscle biopsy, we can see a high amount of ß-glycogen particles with decreased activity of Phosphorylase kinase (11).
GSD Type 9 is known for its genetic complexity, with mutations occurring in specific candidate genes. To accurately diagnose this condition, high-throughput gene sequencing, which involves analyzing many candidate genes together, is the preferred diagnostic method .This advanced method helps doctors find the exact changed genes causing GSD Type 9 very accurately. By checking the activity of liver enzymes in addition to genetic analysis (8). The enzymatic studies are unavailable in Syria, very expensive and not easy to sent biopsy. Whole Exome Sequencing was performed and showed a variant c.801G > A p.(=) In the PHKG2 Gene. This new sequence is classified as variant of uncertain significance. In precision medicine, it's really important to understand how a genetic change affects a patient's health. The mutation corresponds to our condition, so it is compatible with GSD XI.
Regarding treatment, most studies showed that uncooked cornstarch, low_ fat and high_ protein diet are the most helpful treatment for GSD IX patients (14).
Our patient showed a normal growth rate and no fasting hypoglycemia under corn starch and dietary measures, which included avoiding sugar and lipid-rich foods and favoring protein intake. The same measures were applied to his sister. The family could benefit from perinatal genetic diagnosis to avoid giving birth to another child with the same disease, as the risk rate of affected offspring is 25% for autosomal recessive diseases. He showed improvement in development, symptoms, and growth.