Molecular profiles and long-term outcomes of Thai children with hepatic glycogen storage disease in Thailand

BACKGROUND Thus far,genetic analysis of patients clinically diagnosed with glycogen storage diseases(GSDs)in Thailand has not been reported.AIM To evaluate the clinical and biochemical profiles,molecular analysis and long-term outcomes of Thai children diagnosed with hepatic GSD.METHODS Children aged<18 years diagnosed with hepatic GSD and followed up at King Chulalongkorn Memorial Hospital were recruited.Whole-exome sequencing(WES)was performed to identify the causative gene variants.Medical records were assessed.RESULTS All eight children with histopathologically confirmed diagnosis were classified by WES into subtypes Ia(n=1),III(n=3),VI(n=3),and IX(n=1).A total number of 10 variants were identified including G6PC(n=1),AGL(n=4),PYGL(n=5),and PHKA2(n=1).AGL had two novel variants.The clinical manifestations were hepatomegaly(n=8),doll-like facies(n=3),wasting(n=2),and stunting(n=5).All patients showed hypoglycemia,transaminitis,and dyslipidemia.The mainstay of treatment was cornstarch supplementation and high-protein and low-lactosefructose diet.After a median follow-up time of 9.59 years,height turned to normal for age in 3/5 patients and none had malnutrition.Liver enzymes,blood sugar,and lipid profiles improved in all.CONCLUSION Hepatomegaly,transaminitis,and hypoglycemia are the hallmarks of GSD confirmed by liver histopathology.Molecular analysis can confirm the diagnosis or classify the subtype that might benefit from personalized treatment,prognosis,and long-term care.

Mutation analysis and prenatal diagnosis of a family with Griscelli syndrome type 2: two novel mutations in the RAB27A gene

Griscelli syndrome type 2 (GS2;OMIM#607624) is a rare autosomal recessive disorder characterized by hypomelanosis with immunologic abnormalities and haemophagocytic lymphohistocytosis.[1] Neurological manifestations were reported in 67% of GS2 patients.[2]It is caused by mutations in the RAB27A gene.[3] The RAB27A gene encodes Rab27a,a member of the small GTPase superfamily,involved in vesicular fusion and trafficking.[3] Mutations in the MYO5A,RAB27A,or MLPH genes cause GS 1,GS2 or GS3,respectively.It has been demonstrated that the tripartite protein complex (Rab27a/melanophilin/myosin Va) in melanocytes is needed for capturing mature melanosomes for transferring to keratinocytes.