ABSTRACT
OBJECTIVE@#To explore the genetic etiology of a child with D bifunctional protein deficiency (DBPD) born to a consanguineous pedigree.@*METHODS@#A child with DBPD who was admitted to the First Affiliated Hospital of Hainan Medical College on January 6, 2022 due to hypotonia and global developmental delay was selected as the study subject. Clinical data of her pedigree members were collected. Peripheral blood samples of the child, her parents and elder sisters were collected and subjected to whole exome sequencing. Candidate variant was validated by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The child, a 2-year-and-9-month-old female, had featured hypotonia, growth retardation, unstable head lift, and sensorineural deafness. Serum long-chain fatty acids were elevated, and auditory brainstem evoked potentials had failed to elicit V waves in both ears with 90 dBnHL stimulation. Brain MRI revealed thinning of corpus callosum and white matter hypoplasia. The child's parents were secondary cousins. Their elder daughter had a normal phenotype and no clinical symptoms related to DBPD. Elder son had frequent convulsions, hypotonia and feeding difficulties after birth, and had died one and a half month later. Genetic testing revealed that the child had harbored homozygous c.483G>T (p.Gln161His) variants of the HSD17B4 gene, for which both of her parents and elder sisters were carriers. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.483G>T (p.Gln161His) was rated as a pathogenic variant (PM1+PM2_Supporting+PP1+PP3+PP4).@*CONCLUSION@#The homozygous c.483G>T (p.Gln161His) variants of the HSD17B4 gene caused by the consanguineous marriage probably underlay the DBPD in this child.
Subject(s)
Female , Humans , Pedigree , Muscle Hypotonia , Hearing Loss, Sensorineural , Protein Deficiency , MutationABSTRACT
Objective To investigate the clinical features and mechanism and feasibility of plasma exchange (PE) in treating systemic lupus erythematosus (SLE) complicated with acute pancreatitis (AP). Methods A retrospective analysis of SLE associated with AP was done based on the HIS in Tongji Hospital. Totally 24 SLEAP patients were admitted to Tongji hospital from March 2006 to May 2014. Patientsˊ serum amylase, lipase and interleukin (IL)-6 concentration were measured before and after plasma exchange. According to different therapy strategy, patients were divided into two groups. Fifteen patients treated with plasma exchange combination with glucocorticosteroid (GC) were classified as Group A, the other 9 patients who were treated with GC only were classified as group B. At baseline and after treatment, the serum lipid concentration, average daily glucocorticosteroid dosage between group A and B were compared with ANOVA and serum IL-6 concentration between roup A and B were compared with Wilcoxon rank test. Results SLEDAI score in group A patients at baseline (16 ±5) was no statistically different from that in group B (18 ±4) (t=1.31, P=0.320). Average daily GC dosage in group A 31.0 (20.50, 30.08)mg/d was significantly less than that in group B 47.85 (45.58, 59.23) mg/d (Z=35.50, P= 0.002). Serum IL-6 levels in group A and B at baseline was not significantly different 13.14 (11.12,16.57) mg/L vs 14.63 (11.37, 16.37) mg/L (Z=12.20, P=0.300), after 2 weeks treatment, IL-6 level, which was 9.16 (7.93, 10.75) mg/L, decreased significantly in group A while it didnˊt show tendency of decrease in group B, which was 13.62(9.29, 17.63) mg/L (Z=28.50, P=0.039). Serum lipid concentration after 2 weeks therapy in Group A [TC=(5.02 ±0.53) mmol/L, TG=(1.46 ±0.44) mmol/L] decreased significantly compared to baseline [TC=(6.11±0.50) mmol/L, TG=(2.14±0.65) mmol/L] (F=4.46, P=0.010; F=6.09, P=0.002), while similar tendency wasnˊt observed in group B (F=1.57, P>0.05). Conclusion PE combined with GC could lower serum IL-6 levels, reduce the amount of GC and lower serum lipid to improve prognosis. Therefore it might be a safe and effective way and is worthy of continuing to explore its feasibility.