Congenital Neuronal Ceroid Lipofuscinosis with a Novel CTSD Gene Mutation: A Rare Cause of Neonatal-Onset Neurodegenerative Disorder.

Neuronal ceroid lipofuscinoses represent a heterogeneous group of early onset neurodegenerative disorders that are characterized by progressive cognitive and motor function decline, visual loss, and epilepsy. The age of onset has been historically used for the phenotypic classification of this group of disorders, but their molecular genetic delineation has now enabled a better characterization, demonstrating significant genetic heterogeneity even among individuals with a similar phenotype. The rare Congenital Neuronal Ceroid Lipofuscinosis (CLN10) caused by mutations in the CTSD gene encoding for cathepsin D is associated with a dramatic presentation with onset before or around birth. We report on a female born to consanguineous parents who presented at birth with severe neonatal encephalopathy with massive cerebral and cerebellar shrinking on magnetic resonance imaging. Whole exome sequencing with targeted bioinformatic analysis of a panel of genes associated with prenatal/perinatal onset of neurodegenerative disease was performed and revealed the presence of a novel homozygous in-frame deletion in CTSD. Additional functional studies further confirmed the pathogenic character of this variant and established the diagnosis of CLN10 in the patient.

OS014. Which first-line drug to control severe hypertension in pregnancy? A pilot study.

INTRODUCTION: Severe hypertension is a common complication in pregnancy-associated hypertensive disorders and there is no clear consensus on which first-line antihypertensive drug to use in this setting. OBJECTIVES: To determine the efficacy and safety of four antihypertensive drugs (two intravenous and two oral) in pregnant women with severe hypertension. METHODS: Pilot prospective randomised study. INCLUSION CRITERIA: pregnant women with a gestational age >24weeks and admitted in the Obstetrics Department with severe hypertension defined as systolic blood pressure (SBP) ⩾165mmHg and/or diastolic blood pressure (DBP) ⩾105mmHg. The women were randomised in 4 groups to receive:-20mg intravenous labetalol;-5mg intravenous hydralazine;-10mg oral nifedipine tablets ;-10mg sublingual nifedipine. Treatment was repeated every 20mn until target SBP and DBP were reached (⩽150/⩽95mmHg). The primary endpoint was the time needed to achieve effective blood pressure control. Treatment failure was defined as the unability to reach the target BP within one hour. RESULTS: After giving informed consent, 41 pregnant women admitted with severe hypertension were randomised. Mean age was 35 years (SD 3.5), 65% were nulliparous and mean SBP and DBP at admission were 176 (SD 16) and 105 (SD 12)mmHg, respectively. Success to achieve target BP was reached in all patients within the oral 10mg nifedipine group (11 patients), in all but one patients with the 10mg sublingual group (12 patients), and only in 5 out of 9 patients and 6 out of 9 patients within the labetalol and hydralazine groups. They were only one hypotension (defined as SBP <120mmHg) in the two groups with intravenous drugs and 3 and 5 in the oral and sublingual nifedipine groups. CONCLUSION: These results indicate that oral nifedipine seems more effective than intravenous labetalol or hydralazine to reach BP control in pregnant patients with severe hypertension. A large scale randomized trial comparing oral nifedipine versus these commonly used intravenous antihypertensive drugs should be implemented in order to determine whether oral nifedipine is a more effective treatment in this population.

Pre-eclampsia and peripartum cardiomyopathy in molar pregnancy: clinical implication for maternally imprinted genes.

Molar pregnancies are associated with increased maternal complications, notably pre-eclampsia, but peripartum cardiomyopathy has been rarely observed. Here we report on a 34-year-old woman, gravida 2 para 1, who presented to our obstetric clinic for routine screening at 16 weeks of gestation. Elevated maternal serum alpha-fetoprotein and free beta-human chorionic gonadotropin were observed. Amniocentesis revealed a triploid constitution (69,XXX) and ultrasound examination showed growth restriction, fetal anomalies, placentomegaly and a total placenta previa. On admission at 18 weeks' gestation, the patient developed vaginal bleeding and pre-eclampsia. She underwent a Cesarean delivery and 6 h later developed congestive heart failure requiring intensive care support. Molecular analysis of the conceptus and parental DNA demonstrated an excess of paternal genomic contribution. The over-representation of the paternal chromosome complement may support the role of genomic imprinting in the clinical course of this case.