ABSTRACT
Introduction: Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, typically inherited as a recessive trait, is a genetic condition predominantly observed in Central and Eastern Europe, with birth prevalence in Poland amounting to 1/118,336. In most European countries, e.g., in Poland since 2014, this disorder is included in newborn screening. Case Presentation: This paper presents the ophthalmic symptoms of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency in three pediatric patients. Visual acuity testing, fundus photography, and optical coherence tomography (OCT) were performed and data were collected over several years (2017-2022). In case 1, a female born in 2010, exhibited abnormalities in the central part of the posterior pole, mainly in the macula, and included choriocapillaris atrophy and severe disruption of the outer retinal layer. Case 2, a female born in 2012, presented with progressive shortsightedness and choroid atrophy documented with angio-OCT. Case 3, a male born in 2013, experienced recurrent hospitalizations due to metabolic decompensations and presented with mild myopia, thinning of the choroid layer, and slight pigment dispersion with macular sparing. Conclusion: The main ophthalmic symptoms of LCHAD deficiency were choroidal atrophy, disorganization of the outer retinal layer, and myopia. Choroidal atrophy and pigment dispersion were consistently the earliest signs of LCHAD-associated chorioretinopathy. Although the progression of chorioretinopathy in each case resulted from metabolic decompensation, one documented case revealed that not every metabolic crisis results in ophthalmological changes. Nonetheless, strict adherence to a low-fat, high-carbohydrate diet remains crucial to prevent gradual deterioration and vision loss.
ABSTRACT
Intellectual disability with speech delay and behavioural abnormalities, as well as hypotonia, seizures, feeding difficulties and craniofacial dysmorphism, are the main symptoms associated with pathogenic variants of the ZMYND11 gene. The range of clinical manifestations of the ZMYND phenotype is constantly being expanded by new cases described in the literature. Here, we present two previously unreported paediatric patients with neurodevelopmental challenges, who were diagnosed with missense variants in the ZMYND11 gene. It should be noted that one of the individuals manifested with hyperinsulinaemic hypoglycaemia (HH), a symptom that was not described before in published works. The reason for the occurrence of HH in our proband is not clear, so we try to explain the origin of this symptom in the context of the ZMYND11 syndrome. Thus, this paper contributes to knowledge on the range of possible manifestations of the ZMYND disease and provides further evidence supporting its association with neurodevelopmental challenges.
Subject(s)
Abnormalities, Multiple , Intellectual Disability , Child , Humans , Abnormalities, Multiple/genetics , Abnormalities, Multiple/diagnosis , Cell Cycle Proteins/genetics , Co-Repressor Proteins/genetics , DNA-Binding Proteins/genetics , Intellectual Disability/genetics , Intellectual Disability/diagnosis , Mutation, Missense , Phenotype , SyndromeABSTRACT
INTRODUCTION: Atherosclerosis, a precursor to cardiovascular disease (CVD), is deeply intertwined with lipid metabolism. The metabolic process in the Down syndrome (DS) population remain less explored. Aim of the study: This study examines the lipid profiles of DS in comparison to their siblings (CG), aiming to uncover potential atherosclerotic and CVD risks. MATERIAL AND METHODS: The study included 42 people with DS (mean age 14.17 years) and the CG - 20 individuals (mean age 15.92 years). Anthropometric measurements: BMI, BMI SDS, and TMI were calculated. Lipid profile (LP) and metabolomics were determined. RESULTS: LP: DS display significantly reduced HDL (DS vs. CG: 47±10 vs. 59 ±12 mg/dl; p = 0.0001) and elevated LDL (104 ±25 vs. 90 ±22 mg/dl; p = 0.0331). Triglycerides, APO A1, and APO B/APO A1 ratio corroborate with the elevated risk of CVD in DS. Despite no marked differences in: TCH and APO B, the DS group demonstrated a concerning BMI trend. Of 31 identified metabolites, 12 showed statistical significance (acetate, choline, creatinine, formate, glutamine, histidine, lysine, proline, pyroglutamate, threonine, tyrosine, and xanthine). However, only 8 metabolites passed the FDR validation (acetate, creatinine, formate, glutamine, lysine, proline, pyroglutamate, xanthine). CONCLUSIONS: Down syndrome individuals show distinct cardiovascular risks, with decreased HDL and increased LDL levels. Combined with metabolomic disparities and higher BMI and TMI, this suggests an increased atherosclerosis risk compared to controls.
