👤 Maria M van Genderen

Youth with perinatally acquired HIV (PHIV) are at risk for cardiovascular disease (CVD) despite combination anti-retroviral therapy (cART). Longitudinal data on the impact of HIV and cART on lipid metabolism and CVD risk in PHIV youth is limited. We investigated lipid and lipoprotein levels in PHIV youth and matched controls over time and examined associations with cART and metabolic syndrome (MetS) markers. We included 32 PHIV and 36 controls at three time points: 2013, 2018 and 2023. In 2023, we assessed lipid profiles cross-sectionally in a larger cohort of 53 PHIV participants and 45 controls. Measurements included lipoprotein (a) (Lp(a)), apolipoprotein B (ApoB), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), reduced high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC) and markers related to MetS risk. The median age was 21.7 years (IQR 16.7-25.2) for PHIV participants and 21.2 years (16.8-22.3) for controls in 2023 for longitudinal assessment. No significant differences in lipid or lipoprotein levels were observed over time (p values > 0.05). TG levels were significantly higher in PHIV participants at second assessment (p = 0.043), but other levels were comparable (p values > 0.05). Higher Lp(a) levels were associated with higher LDL-C and ApoB levels, however associations were significantly weakened among PHIV participants. Furthermore, protease inhibitor (PI) use was associated with elevated TC, TG and LDL-C. During cross-sectional assessment median age was 17.4 years (IQR 12.7-22.4) and 19.1 years (IQR 15.0-21.8) for PHIV youth and controls. Lipid and MetS markers were comparable between groups (p values > 0.05). PHIV youth on cART showed similar lipid and lipoprotein levels over time compared to matched controls. Lp(a) associations with lipid markers were weakened for PHIV youth and PI use was associated with lipid alterations. Our results imply that while lipid profiles, including Lp(a), are important components of cardiovascular health monitoring, the increased CVD risk observed in PHIV youth may be more substantially influenced by disease-specific or broader pathophysiological mechanisms related to HIV-infection and treatment. Dutch clinical trial registration: Overview of Medical Research in the Netherlands (OMON) (ID: NL-OMON53727). Show less

To help differentiate CLN3 (Batten) disease, a devastating childhood metabolic disorder, from the similarly presenting early-onset Stargardt disease (STGD1). Early clinical identification of children with CLN3 disease is essential for adequate referral, counselling and rehabilitation. Medical chart review of 38 children who were referred to a specialized ophthalmological centre because of rapid vision loss. The patients were subsequently diagnosed with either CLN3 disease (18 patients) or early-onset STGD1 (20 patients). Both children who were later diagnosed with CLN3 disease, as children who were later diagnosed with early-onset STGD1, initially presented with visual acuity (VA) loss due to macular dystrophy at 5-10 years of age. VA in CLN3 disease decreased significantly faster than in STGD1 (p = 0.01). Colour vision was often already severely affected in CLN3 disease while unaffected or only mildly affected in STGD1. Optic disc pallor on fundoscopy and an abnormal nerve fibre layer on optical coherence tomography were common in CLN3 disease compared to generally unaffected in STGD1. In CLN3 disease, dark-adapted (DA) full-field electroretinogram (ERG) responses were either absent or electronegative. In early-onset STGD1, DA ERG responses were generally unaffected. None of the STGD1 patients had an electronegative ERG. Already upon presentation at the ophthalmologist, the retina in CLN3 disease is more extensively and more severely affected compared to the retina in early-onset STGD1. This results in more rapid VA loss, severe colour vision abnormalities and abnormal DA ERG responses as the main differentiating early clinical features of CLN3 disease. Show less

CLN3 disease is a major cause of childhood neurodegeneration. Onset of visual failure around 6 years of age is thought to precede cognitive deterioration by a few years, but casuistic reports question this paradigm. The aim of our study is to delineate timing of cognitive decline in CLN3 disease. Early neurocognitive functioning in CLN3 disease was analyzed using age at onset of visual and cognitive decline and IQ scores from literature-derived patient descriptions, supplemented with IQ scores and school history from a retrospective referral center cohort. We analyzed protracted and classical CLN3 separately and added a control group of patients diagnosed with juvenile onset macular degeneration (early onset Stargardt disease) to control for possible effects of rapid vision loss on neurocognitive functioning. Onset of cognitive decline at a mean age of 6.8 years (range 2-13 years, n = 19) paralleled onset of visual deterioration at a mean age of 6.4 years (range 4-9 years, n = 81) as supported by an early decline in IQ scores in classical CLN3 disease. Onset and course of vision loss was similar in patients with protracted CLN3. The decreased IQ levels at diagnosis (mean 68.4, range 57-79, n = 9) in the referral cohort were consistently associated with an aberrant early school history contrasting normal school history and cognition in Stargardt disease patients. Cognitive dysfunction is universally present around diagnosis in classical CLN3 disease. Show less