Fucosidosis is a rare neurodegenerative autosomal recessive disorder, which manifests as progressive neurological and psychomotor deterioration, growth retardation, skin and skeletal abnormalities, intellectual disability and coarsening of facial features. It is caused by biallelic mutations in FUCA1 encoding the α-L-fucosidase enzyme, which in turn is responsible for degradation of fucose-containing glycoproteins and glycolipids. FUCA1 mutations lead to severe reduction or even loss of α-L-fucosidase enzyme activity. This results in incomplete breakdown of fucose-containing compounds leading to their deposition in different tissues and, consequently, disease progression. To date, 36 pathogenic variants in FUCA1 associated with fucosidosis have been documented. Among these are three splice site variants. Here, we report a novel fucosidosis-related 9-base-pair deletion (NG_013346.1:g.10233_10241delACAGGTAAG) affecting the exon 3/intron 3 junction within a FUCA1 sequence. This novel pathogenic variant was identified in a five-year-old Polish girl with a well-defined pattern of fucosidosis symptoms. Since it is postulated that other genetic, nongenetic or environmental factors can also contribute to fucosidosis pathogenesis, we performed further analysis and found two rare de novo chromosomal aberrations in the girl’s genome involving a 15q11.1-11.2 microdeletion and an Xq22.2 gain. These abnormalities were associated with genome-wide changes in DNA methylation status in the epigenome of blood cells.

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Prenatal alcohol exposure causes growth impairment and a wide range of developmental, physical, and cognitive disorders in children, collectively referred to as fetal alcohol spectrum disorders (FASDs). In the course of FASDs, abnormalities can also affect eating behavior and nutritional status, but these problems have received little attention. Therefore, the aim of our study was to determine the levels of hormones involved in the action of the hypothalamic–pituitary–adrenal axis: proopiomelanocortin (POMC), cortisol, and adrenocorticotropic hormone (ACTH), in the serum of patients with FASDs. To our knowledge, none of these hormones studied have yet been evaluated in FASDs to date. We investigated 62 FASD patients and 23 healthy controls by applying an enzyme-linked immunosorbent method (ELISA). Fasting POMC levels were significantly lower in patients with FASDs (10.97 vs. 18,57 ng/mL, p = 0.039) compared to controls. However, there were no differences in cortisol concentrations. Additionally, the sex and subgroup status (fetal alcohol syndrome (FAS), neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE), and FASD risk) did not affect hormone levels. POMC was positively correlated with some clinical parameters such as age, BMI percentile, carbohydrate biomarkers, and ACTH. A positive correlation was observed between ACTH and cortisol levels, as well as ACTH and cholesterol levels. Data analysis showed no HPA axis abnormalities in the form of elevated serum cortisol and ACTH levels. Differences in POMC concentration may indicate the involvement and/or impairment of central nervous system structures in hormonal alterations in FASD individuals, caused by prenatal alcohol exposure. Hormonal dysregulation in FASDs can contribute to reduced growth and development, as well as many other disturbed processes, including neurological/neurodevelopmental dysfunctions. Further insightful studies involving a larger group of patients are needed to determine the potential impact of the measured hormones.

IntroductionFetal alcohol spectrum disorders (FASDs) are a leading preventable cause of developmental and psychosocial disorders. Prenatal alcohol exposure can be a cause of growth impairment and metabolic problems. In this study, we analyzed data on the growth, weight, and nutritional status of children with FASD.MethodsPatients were recruited from the Department of Pediatrics, Pediatric Endocrinology and Diabetology, and the Outpatient Endocrinology Clinic in Rzeszów, Poland. Each person referred for evaluation had a diagnosis of FASD based on the recommendations of Polish experts. The population consisted of 59 subjects with measurements of weight and height, and the IGF-1 level test was performed.ResultsChildren with FAS had consistently lower height and weight measurements than children with ND-PAE. In the FAS group, children (<3 percentile) accounted for 42.31%, and in the ND-PAE group – 18.18%. The analysis of the whole group showed the highest prevalence of low body weight (below the third percentile) among subjects with FAS – 53.85%. The prevalence of low body weight and short stature (both parameters <3rd centile) was found to be 27.11% in the whole group. Lower mean BMI values were related to the FAS group (21.71 kg/m2) compared to the ND-PAE group (39.62 kg/m2). In the study group, BMI below the fifth percentile was found in 28.81% of the children, normal weight (5th-85th percentile) in 67.80%.DiscussionDuring the care of children with FASD, a continuous evaluation of nutritional status, height, and weight is necessary. This group of patients is often affected by low birth weight, short stature and weight deficiency, which require differential diagnosis and appropriate dietary and therapeutic management.