| Objective: To analyze and summarize the clinical characteristics and follow-up of glycogen storage disease,so as to improve clinicians' understanding of glycogen storage disease,improve their diagnosis and treatment level,and reduce the occurrence of missed diagnosis,misdiagnosis and mistreatment.Objects and Methods: Collected the patients with glycogen storage disease of the children's hospital affiliated to Chongqing medical university from January 2007 to March 2019.Follow-up of nutritional management and prognosis of children,and summarize the clinical characteristics of children with glycogen storage disease.Results:(1)72 children with glycogen storage disease were included in this study,including 48/72 cases with clinical diagnosis and 24/72 cases with genetic diagnosis.There were 48/72 cases males and 24/72 cases females.Age of onset: males were 1.75 years(0.83~2.42)and females 1.25 years(0.38~2.33).Age of diagnosis: male 2.50(1.54~3.96)years old,female 3.21(1.21~4.79)years old,gender composition in the age of diagnosis was not statistically significant(P>0.05).(2)There were 7 cases(3 males and 4 females)with age < 1 years old,33 cases(27 males and 6 females)with age 1-3 years old,and 32 cases(18 males and 14 females)with age 3-14 years old.The incidence rate of males in the group aged 1-3 years was higher than that in the group aged over 3 years old,and the gender composition between the remaining age groups was not statistically significant(P > 0.05).(3)54/72 cases were found because of abdominal distension,liver,spleen enlargement and(or)for the first symptom such as abnormal liver function in hospital,3/72 cases for yellowing found skin hospital,2/72 cases with convulsions,coma in hospital since morning repeatedly,2/72 cases for short stature is complained of a hospital,10/72 cases because of fever,cough,abdominal pain,diarrhea,loss of appetite,fatigue,such as hospital,1/72 cases due to hematemesis(ruptured esophageal gastric varices bleeding)in hospital.(4)3/72 cases had total developmental retardation,11/72 cases had motor retardation alone,4/72 cases had language retardation alone.19/72 cases had low body weight,35/52 cases had short stature,63/72 cases had liver enlargement on physical examination,and 31/63 cases had splenomegaly on physical examination.12/72 cases always prone to respiratory infections,6/72 cases always have repeatedly diarrhea,9/72 cases has a history of epistaxis,3/72 cases has a history of convulsions or disturbance of consciousness,1/72 cases with clear history of neonatal hypoglycemia,7/72 cases poor or lack of everyday activity,1 /72 cases have repeatedly oral ulcer,small is more common than low weight,and the older son shorter than infants and young children.(5)Blood routine examination indicated decreased hemoglobin in 42/72 cases,neutropenia in 4/72 cases,and thrombocytopenia in 2/72 cases.ALT was elevated in 65/72 cases.There were 66/72 cases with elevated AST.Blood triglycerides were elevated in 43/56 cases,among which 10/43 cases were also associated with elevated total cholesterol.Elevated serum ammonia was found in 24/56 cases.Blood lactic acid increased in 42/60 cases.Elevated uric acid was found in 26/70 cases.There were 14/64 cases with positive urinary ketone body,5/64 cases with positive urinary protein,53/67 cases with fasting hypoglycemia(0.31-3.76 mmol/L),and blood glucose <2.80mmol/L was more common(30/67 cases).There was no statistically significant difference in the degree of hypoglycemia between different age groups(P>0.05).(6)Color doppler ultrasound of the liver in 9/60 cases indicated enhanced echo,and 45/60 cases showed moderate to severe enlargement(? 3cm).There was no statistically significant difference in the degree of liver enlargement between infants and older children(P>0.05).Liver fibrosis was suggested in 2/39 cases.There were 25/60 cases with enlarged spleen,and 2/25 cases with enhanced spleen echo.In 6/60 cases,bilateral renal echo enhancement was found,among which 2/6 cases presented diffuse lesions in both kidneys.(7)Hepatic puncture: the results of light microscopy showed that hepatocyte swelling was obvious in 50/52 cases.There were 22/52 cases with intercalated plant arrangement.Spotty necrosis was found in 15/52 cases,and regenerated hepatocytes were found in 4/52 cases.There were 29/52 cases with different degrees of fibrosis,among which 8/29 cases showed obvious hepatic fibrosis.Hepatic sinus compression,stenosis or occlusion were observed in 28/52 cases.In 37/52 cases,a little inflammatory cell infiltration was observed in the lobule or portal area,and in 10/52 cases,scattered inflammatory cell infiltration was observed.3/52 cases showed varying degrees of cholestasis.PAS staining was complete in 41 cases,PAS staining was positive in 23/41 cases and focal positive or weak positive in 15/41 cases.PAS stain was negative in 3/41 cases patients.Under electron microscope,the hepatocyte volume increased in 22/23 cases,and the glycogen level increased in 17/23 cases.Cytoplasmic and cytoplasmic cavitation were observed in 11/23 cases.Lipid droplet deposition was observed in 16/23 cases.Collagen fiber proliferation was observed in 17/23 cases,among which 5/17 cases indicated obvious liver fibrosis.Other organelles were significantly reduced in 7/23 cases,and medullary structures were increased in 1/23 cases,in another 1/23 cases,the clumps of immature cells were observed in the interstitial area.(8)There were 24 cases which have the genes report,7/24 cases were GSD-?,of which 3/7 cases had homozygous mutations on G6 PC gen,2/7 cases had two hybrid mutation on G6 PC gen,1/7 cases did not know the information of mutation site.Among of 7cases,4cases had specific mutations: 2/4 cases had c.648 G > T homozygous mutations;One fourth cases of had c.146 T > A homozygous mutations;1/4 cases had c.248 G> A and c.992 c > T heterozygous mutations.6/7 cases of GSD-I type which uric acid increased significantly.3/3 cases of liver puncture suggests that have different degree of liver fibrosis.In these 24 patients,2/24 cases were GSD-?(and in this 2 cases,the level of lactic acid were moderately elevated),1/2 cases had c.853 C>T homozygous mutations in AGL gen,1/2 cases had two hybrid mutation(c.83-1 G>A and c.4284 T>G heterozygous mutations).Among the 24 cases mentioned above,4/24 cases were hepatic GSD-?.8/24 cases were hepatic GSD-?(7/8 cases of male,1/8 case of female).The 7 male cases had hemizygous mutations in PHKA2 gen,5/7 cases were traced to specific mutations: 2/5 cases had c.883 C>T hemizygous mutation;1/5 cases had c.568 G>A hemizygote mutation;1/5 cases had c.1462 C>T hemizygote mutation;1/5 cases had c.3344-3345 insCCC hemizygous mutations,and those 7 boys were liver GSD-?a.1/8 cases(the girl)had mutation in PHKG2 gen,she was liver GSD-?c.In addition,1/24 cases of genotype report tips was liver GSD-?(Fanconi-Bickel syndrome),had homozygous mutations in SLC2A2 gen.Something else needs to be added: 2/24 cases were diagnosed with glycogen accumulation syndrome,but the parents of those 2cases didn't know the disease type.(9)A total of 27 children(19 males and 8 females)were included in the follow-up study.The follow-up time ranged from 1 month to 5 years,including 2/27 cases(2 males)from 1 month to 3 months,6/27 cases(4 males and 2 females)from 3 months to 1 year,6/27 cases(4 males and 2 females)from 1 year to 3 years,and 13/27 cases(9 males and 4 females)from 3 years to 5 years.18/27 cases(15 males and 3 females)were fed normal raw corn starch,and 9/27 cases(4 males and 5 females)were fed unnormal raw corn starch.The patients were divided into the formal treatment group and the informal treatment group.The weight,liver function(ALT)and liver size of the children in the formal treatment group were significantly better than those in the informal treatment group.Long-term oral raw corn starch feeding was significant for the improvement of the height of the children.Blood sugar also improved,but the data are in doubt.Informal treatment group some of the children also have a better prognosis,especially the children of GSD-?,?a.(10)Before the clinical diagnosis of liver glycogen accumulating disease relies mainly on the clinical manifestation,blood biochemical examination,general examination of abdomen colour to exceed,etc.,with the development of liver biopsy and gene examination,liver glycogen accumulating significant diagnostic standard,genetic testing for evaluation of liver lesions cannot fully replace the liver biopsy,the diagnosis and evaluating the needs at the same time,combined with clinical and liver biopsy and genetic tests.Conclusions: When it is found that the child has hepatomegaly,elevated aminotransferase,fasting hypoglycemia(or hypoglycemia attack),growth and development lag,etc.,it should to be alert to the possibility of liver glycogen storage disease.At the same time,combined with clinical manifestations,liver puncture and genetic examination,it can better diagnose,classify and differentiate glycogen storage disease from other diseases.Nutritional management and metabolic control should be carried out as soon as possible after diagnosis,and long-term treatment and follow-up should be carried out. |
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