👤 Serafina Di Giacomo

Acute hyperlipidaemic pancreatitis (HP) may develop in pregnancy in patients with genetic predisposition. There are no accepted guidelines for the management of this rare but life-threatening condition in pregnancy. Plasma exchange (PEX) was suggested as a suitable option to treat HP in pregnancy; however, further evidence from case reports/case series are needed. Three PEX procedures (2000 ml of plasma replaced with 5% albumin) were performed in one week in a pregnant patient at 25 weeks of gestational age with severe HP. Triglyceride related genes (LPL, APOA5, APOE, GPIHBP1, GPD1, LMF1, CREB3L3) were screened by DNA sequencing. Medline and Embase databases were searched electronically in January 2018 using different combinations of the relevant medical subject headings for "pancreatitis in pregnancy" and "therapeutic apheresis". Gene profiling assessed a combined heterozygous state for the variants pSer19Trp of the APOA5 gene and pCys130Arg of the APOE (allele E4) gene. PEX led to significant and progressive reduction of triglyceride plasma levels along with cholesterol and C-reactive protein. Meanwhile a fast improvement of pregnant clinical condition was observed. This allowed the delivery at term of a healthy newborn without gestational complications. An outcome hardly achievable in patients managed exclusively by a pharmacological approach. PEX led to a positive maternal outcome in absence of foetal and gestational complications in a case of severe HP in pregnancy. As clinical trials are lacking, case reports still represent the best way to reasonably implement clinical management of this rare but life-threatening disease. Show less

Chylomicronemia syndrome presenting in childhood is a rare recessive disorder due to mutations of lipoprotein lipase (LPL) and more rarely of APOC2, APOA5, GPIHBP1 or LMF1 genes. It often requires urgent and suitable treatment to avoid acute pancreatitis. The aim of this study was the molecular characterization and treatment of a 3 month-old infant with plasma triglycerides (TG) > 300 mmol/L. All candidate genes were sequenced. The patient was submitted to one plasma-exchange (PEX) procedure and subsequently to a rigid lipid-lowering diet (milk: Monogen(®)). The proband was homozygous for a novel LPL mutation (c.242G > A, p.G81D) which in silico results pathogenic. After PEX, which was well tolerated, TG dropped to 64 mmol/L. During 5-month follow-up there was a clear trend towards lower and stable TG values. PEX is applicable in subjects with very low body weight when the extreme severity of the clinical picture has no therapeutic alternatives. Show less

The MLLT10 gene, located at 10p13, is a known partner of MLL and PICALM in specific leukemic fusions generated from recurrent 11q23 and 11q14 chromosome translocations. Deep sequencing recently identified NAP1L1/12q21 as another MLLT10 partner in T-cell acute lymphoblastic leukemia (T-ALL). In pediatric T-ALL, we have identified 2 RNA processing genes, that is, HNRNPH1/5q35 and DDX3X/Xp11.3 as new MLLT10 fusion partners. Gene expression profile signatures of the HNRNPH1- and DDX3X-MLLT10 fusions placed them in the HOXA subgroup. Remarkably, they were highly similar only to PICALM-MLLT10-positive cases. The present study showed MLLT10 promiscuity in pediatric T-ALL and identified a specific MLLT10 signature within the HOXA subgroup. Show less