👤 Ferda Ozkinay

The combination of acute pancreatitis (AP), severe hypertriglyceridemia (HTG), and diabetic ketoacidosis (DKA) poses a life-threatening triad. Although DKA is a frequent complication in children, this triad is rare. We report a 10-year-old girl with type 1 diabetes mellitus (T1DM) for 10 months, who presented with DKA, severe HTG, and AP. Her serum was lipemic. She had HTG (1733 mg/dl, 19.5 mmol/L; reference range, 90-129 mg/dl, 1,016-1,456 mmol/L) and severe abdominal pain that did not improve despite treatment for ketoacidosis. She had high lipase levels (1581 U/L, reference range 28-100 U/L), and pancreatitis was detected on abdominal tomography. She recovered with a combination of hydration and insulin therapy. A heterozygous p.N318S (c.953A>G) variant was detected in her lipoprotein lipase (LPL) gene. Her apolipoprotein B (ApoB) was elevated at 1.44 g/L (reference range, 0.6-1.17 g/L, 60-117 mg/dl). It is well established that both the likely pathogenic LPL variants and high ApoB concentrations contribute to an increased risk of cardiovascular complications. Therefore, it is recommended to evaluate for a pathogenic variant in the LPL gene in children with T1DM who do not have dyslipidemia but exhibit the rare triad of AP, HTG, and DKA. Show less

Koolen-de Vries syndrome (KdVS) is a rare multisystemic disorder caused by a microdeletion on chromosome 17q21.31 including KANSL1 gene or intragenic pathogenic variants in KANSL1 gene. Here, we describe the clinical and genetic spectrum of eight Turkish children with KdVS due to a de novo 17q21.31 deletion, and report on several rare/new conditions. Eight patients from unrelated families aged between 17 months and 19 years enrolled in this study. All patients evaluated by a clinical geneticist, and the clinical diagnosis were confirmed by molecular karyotyping. KdVS patients had some common distinctive facial features. All patients had neuromotor retardation, and speech and language delay. Epilepsy, structural brain anomalies, ocular, ectodermal, and musculoskeletal findings, and friendly personality were remarkable in more than half of the patients. Hypertension, hypothyroidism, celiac disease, and postaxial polydactyly were among the rare/new conditions. Our study contributes to the clinical spectrum of patients with KdVS, while also provide a review by comparing them with previous cohort studies. Show less

Bardet-Biedl Syndrome (BBS) is a rare, autosomal-recessive ciliopathy characterized by obesity, rod-cone dystrophy, postaxial polydactyly, renal abnormalities, genital abnormalities and learning difficulties. To date, mutations in 21 different genes have been described as being responsible for BBS. Recently sequential gene sequencing has been replaced by next generation sequencing (NGS) applications. In this study, 15 patients with clinically diagnosed BBS were investigated using a next generation sequencing panel which included 17 known BBS causing genes (BBS1, BBS2, ARL6, BBS4, BBS5, MKKS, BBS7, TTC8, BBS9, BBS10, TRIM32, BBS12, MKS1, NPHP6, WDPCP, SDCCAG8, NPHP1). A genetic diagnosis was achieved in 13 patients (86.6%) and involved 9 novel and 3 previously described pathogenic variants in 6 of 17 BBS causing genes. BBS10 and BBS1 were the most commonly involved genes with frequencies of 31% and 23% respectively. Three of the 13 patients had an affected sibling. All affected siblings were found to be homozygous for the mutation detected in the proband. No evidence of triallelic inheritance was detected. Although limited association between certain genes and phenotypic features has been observed in this study, it is considered that additional studies are needed to better characterize the genotype-phenotype correlation of BBS. Our results demonstrate that NGS panels are feasible and effective method for providing high diagnostic yields in the diseases caused by multiple genes such as BBS. Show less