Novel compound heterozygous mutations in the hemojuvelin gene in a juvenile hemochromatosis patient:A case report

BACKGROUND Juvenile hemochromatosis(JH)is an early-onset,rare autosomal recessive disorder of iron overload observed worldwide that leads to damage in multiple organs.Pathogenic mutations in the hemojuvelin(HJV)gene are the major cause of JH.CASE SUMMARY A 34-year-old male Chinese patient presented with liver fibrosis,diabetes,hypogonadotropic hypogonadism,hypophysis hypothyroidism,and skin hyperpigmentation.Biochemical test revealed a markedly elevated serum ferritin level of 4329μg/L and a transferrin saturation rate of 95.4%.Targeted exome sequencing and Sanger sequencing revealed that the proband had a novel mutation c.863G>A(p.R288Q)in the HJV gene which was transmitted from his father,and two known mutations,c.18G>C(p.Q6H)and c.962_963delGCinsAA(p.C321*)in cis,which were inherited from his mother.The p.R288W mutation was previously reported to be pathogenic for hemochromatosis,which strongly supported the pathogenicity of p.R288Q reported for the first time in this case.After 72 wk of intensive phlebotomy therapy,the patient achieved a reduction in serum ferritin to 160.5μg/L.The patient's clinical symptoms demonstrated a notable improvement.CONCLUSION This study highlights the importance of screening for hemochromatosis in patients with diabetes and hypogonadotropic hypogonadism.It also suggests that long-term active phlebotomy could efficiently improve the prognosis in severe JH.

Factors associated with improvement in waist-to-height ratio among newly diagnosed type 2 diabetes patients treated with acarbose or metformin:A randomized clinical trial study

BACKGROUND The waist-to-height ratio(WHtR)is a promising anthropometric measure used to evaluate cardiovascular risk in diabetes and metabolic syndrome patients.The metformin and acarbose in Chinese as the initial hypoglycaemic treatment trial demonstrated that acarbose and metformin reduced the WHtR after 24 wk of treatment.AIM To investigate the factors associated with a decrease in the WHtR in newly diagnosed Chinese type 2 diabetes patients receiving acarbose or metformin monotherapy.METHODS At 24 wk,343 patients in the acarbose treatment and 333 patients in the metformin treatment were included in this analysis.On the basis of the reduction in the WHtR,these participants were divided into the following two groups:LowΔWHtR group and highΔWHtR group.Metabolic and related parameters associated with a highΔWHtR were investigated using univariate and multivariate logistic regression analyses.RESULTS A significant decrease in the WHtR was observed in both treatment groups(acarbose:-0.015,95%confidence interval[CI]:-0.018 to-0.012,P<0.001;metformin:-0.013,95%CI:-0.016 to-0.010,P<0.001).In both the acarbose and metformin groups,the WHtR of the women was more likely to be reduced than that of the men.In the acarbose group,a lower baseline area under the curve of glucagon-like peptide 1(AUCGLP-1)was associated with a highΔWHtR(odds ratio[OR]=0.796,P<0.001),while a higher baseline AUCGLP-1 was associated with a highΔWHtR in the patients treated with metformin(OR=1.133,P=0.025).Regarding the changes from baseline,an increase in AUCGLP-1 was associated with a highΔWHtR in the acarbose(OR=1.121,P=0.016)but not metformin group.A higher reduction in high-density lipoprotein cholesterol/non-highdensity lipoprotein cholesterol was also associated with a highΔWHtR in the acarbose arm(OR=20.735,P=0.001).In the metformin arm,a higher reduction in fasting plasma glucose(OR=0.843,P=0.039)and total cholesterol was associated with a highΔWHtR(OR=0.743,P=0.013).CONCLUSION A lower glucagon-like peptide 1 level and higher increase in glucagon-like peptide 1 are associated with a high reduction in the WHtR in newly diagnosed Chinese diabetes patients receiving treatment with acarbose.