ABSTRACT
BACKGROUND: Cholesterol ester storage disorder (CESD; OMIM: 278,000) was formerly assumed to be an autosomal recessive allelic genetic condition connected to diminished lysosomal acid lipase (LAL) activity due to LIPA gene abnormalities. CESD is characterized by abnormal liver function and lipid metabolism, and in severe cases, liver failure can occur leading to death. In this study, one Chinese nonclassical CESD pedigree with dominant inheritance was phenotyped and analyzed for the corresponding gene alterations. METHODS: Seven males and eight females from nonclassical CESD pedigree were recruited. Clinical features and LAL activities were documented. Whole genome Next-generation sequencing (NGS) was used to screen candidate genes and mutations, Sanger sequencing confirmed predicted mutations, and qPCR detected LIPA mRNA expression. RESULTS: Eight individuals of the pedigree were speculatively thought to have CESD. LAL activity was discovered to be lowered in four living members of the pedigree, but undetectable in the other four deceased members who died of probable hepatic failure. Three of the four living relatives had abnormal lipid metabolism and all four had liver dysfunctions. By liver biopsy, the proband exhibited diffuse vesicular fatty changes in noticeably enlarged hepatocytes and Kupffer cell hyperplasia. Surprisingly, only a newly discovered heterozygous mutation, c.1133T>C (p. Ile378Thr) on LIPA, was found by gene sequencing in the proband. All living family members who carried the p.I378T variant displayed reduced LAL activity. CONCLUSIONS: Phenotypic analyses indicate that this may be an autosomal dominant nonclassical CESD pedigree with a LIPA gene mutation.
ABSTRACT
OBJECTIVE: To investigate the clinical efficacy and safety of "3+7" regimen and decitabine + HAG pre-excitation regimen in the treatment of elderly MDS patients with AML transformed by abnormal proliferation of bone marrow. METHODS: Fifty elderly patients with AML transformed by abnormal proliferation of bone marrow in the period from March 2012 to May 2014 were chosen and randomly divided into 2 groups including A group (25 elderly patients treated with "3+7" regimen) and B group (25 elderly patients treated with decitabine+HAG pre-excitation regimen), and the clinical effeicacy, the median survival time and the incidence of drug adverse effects in 2 groups were compared. RESULTS: The clinical total remission rate in B group was significantly higher than that in A group(P<0.05). The leukopenia time, neutropenia time and recovery time of leukocyte and neutrophilia in B group were significantly shorter than those in A group, the differences were statistically significant (P<0.05). The rate of lung infection in B group was significantly lower than that in A group. There was no significant difference in the incidence of other drug adverse effects between 2 groups(P>0.05). The life quality of patients in B group was significantly prior to patients in A group, and the difference was statistically significant (P<0.05). The average survival time and the median survival time of patients in B group was significantly longer than those in A group(P<0.05). CONCLUSION: Compared with "3+7" regimen, the decitabine+HAG pre-excitation regimen in the treatment of elderly patients with AML transformed by abnormal proliferation of bone marrow can efficiently delay the disease progression process, shorten the time of bone marrow suppression, decrease the rate of lung infection and prolong the survival time.
