Serum butyrylcholinesterase/HDL-cholesterol ratio and atherogenic index of plasma in patients with fatty liver disease.

Cardiovascular diseases on an atherosclerotic basis are a serious health problem. Atherosclerosis is a multifactorial pathological process with complex pathogenesis. Its origin and development is conditioned by a set of several risk factors. Changes in the spectrum of lipoproteins are one of the well-known, serious risk factors for cardiovascular disease. The results of several authors showed, that the examination of the ratio of some lipoproteins can provide more accurate information about the cardiovascular risk in a given individual than the individual lipid parameters alone. Non-alcoholic fatty liver disease (NAFLD) is currently the most common form of chronic hepatopathy. The aim of our study was to examine lipoprotein ratios - atherogenic index of plasma (AIP) and butyrylcholinesterase/ HDL-cholesterol ratio - in patients with NAFLD and to evaluate their changes in relation to the severity of hepatic steatosis. The study group consisted of 64 patients with hepatic steatosis, 32 men and 32 women. Patients were examined for fatty liver index (FLI), with FLI values above 60.0 signaling the presence of steatosis. From the biochemical parameters, we examined the serum concentrations of total cholesterol, HDL- and LDL-cholesterol, triacylglycerols and butyrylcholinesterase activity in patients with fatty liver disease. As the results of our study showed, both basic lipid parameters - total cholesterol and triacylglycerols - were increased in patients with hepatic steatosis compared to the values in the control group (Chol: 3,59 ± 0,16 vs. 5,14 ± 0,14 mmol/l; TAG: 0,85 ± 0,06 vs. 1,86 ± 0,14 mmol/l). Both investigated lipoprotein ratios - AIP and the BChE / HDL-cholesterol ratio were also significantly increased in patients with liver steatosis (AIP: -0,191 ± 0,04 vs. 0,157 ± 0,04; BChE/HDL-C: 3171 ± 123 vs. 4602 ± 291). The value of the BChE/HDL-cholesterol ratio correlated well with the total cholesterol/HDL cholesterol ratio (correl.coeff. 0,802) as well as with the atherogenic index of plasma (correl.coeff. 0,702). The findings of elevated AIP and BChE/HDL-C ratios confirmed the hypothesis of an increased risk of cardiovascular disease in patients with fatty liver disease. The finding of a significant positive correlation between AIP and BChE/HDL-C on the one hand and fatty liver index (FLI) on the other hand suggests that cardiovascular risk increases with the severity of steatotic liver injury.

An unusually high frequency of SCAD deficiency caused by two pathogenic variants in the ACADS gene and its relationship to the ethnic structure in Slovakia.

BACKGROUND: Short-chain acyl-CoA dehydrogenase deficiency (SCADD) represents a rare autosomal recessive inborn metabolic disorder of mitochondrial ß-oxidation of monocarboxylic acids. Clinical symptoms can vary from a severe life-threatening condition to an asymptomatic state, reported in the majority of cases. Since the expansion of newborn screenings, more than three hundred probands were admitted for molecular-genetic analysis, most selected because of elevated values of C4-acylcarnitine detected in newborn screenings in Slovakia. Searching for the principal genomic changes led us to the selection of sixty-two patients in whom the presence of sequence variants in the ACADS gene was analysed and correlated with the available biochemical and clinical data. METHODS: Biochemical and molecular genetic tests were performed. Acylcarnitine profiles focused on an elevated level of C4-acylcarnitine, which was analysed via tandem mass spectrometry. Urinary organic acids, specifically a quantity of ethylmalonic acid, were determined by gas chromatography/mass spectrometry. The entire coding region of the ACADS gene was sequenced. A low-cost restriction fragment length polymorphism of PCR amplified fragments analysis (PCR-RFLP) of pathogenic variants was introduced and implemented for the molecular-genetic algorithm appropriate for the Slovak population. RESULTS: Our molecular genetic study was performed on sixty-two patients with a pathological biochemical pattern related to short-chain acyl-CoA dehydrogenase deficiency. In this cohort, we discovered a high occurrence of two rare pathogenic variants-the deletion c.310_312delGAG and the substitution c.1138C>T, with allelic frequencies of 64% and 31%, respectively. Up to 86% of investigated individuals belong to the Roma ethnic group. CONCLUSIONS: Analogous to other countries, SCADD is not included in the newborn screening programme. Based on the exceeded levels of the specific biomarker C4-acylcarnitine as well as ethylmalonic acid, we revealed a high prevalence of short-chain acyl-CoA dehydrogenase deficiency cases, confirmed by the findings of two rare pathogenic variants. A deletion c.310_312delGAG and c.1138C > T substitution in the ACADS gene appear with a high frequency in the Roma ethnic group of Slovakia. Due to the uncertainty of the pathogenicity and clinical consequences, it is important to follow up the morbidity and mortality in these patients over time and evaluate SCADD in relation to clinical outcomes and preventive healthcare recommendations.

Severe child form of primary hyperoxaluria type 2 - a case report revealing consequence of GRHPR deficiency on metabolism.

BACKGROUND: Primary hyperoxaluria type 2 is a rare monogenic disorder inherited in an autosomal recessive pattern. It results from the absence of the enzyme glyoxylate reductase/hydroxypyruvate reductase (GRHPR). As a consequence of deficient enzyme activity, excessive amounts of oxalate and L-glycerate are excreted in the urine, and are a source for the formation of calcium oxalate stones that result in recurrent nephrolithiasis and less frequently nephrocalcinosis. CASE PRESENTATION: We report a case of a 10-month-old patient diagnosed with urolithiasis. Screening of inborn errors of metabolism, including the performance of GC/MS urine organic acid profiling and HPLC amino acid profiling, showed abnormalities, which suggested deficiency of GRHPR enzyme. Additional metabolic disturbances observed in the patient led us to seek other genetic determinants and the elucidation of these findings. Besides the elevated excretion of 3-OH-butyrate, adipic acid, which are typical marks of ketosis, other metabolites such as 3-aminoisobutyric acid, 3-hydroxyisobutyric acid, 3-hydroxypropionic acid and 2-ethyl-3-hydroxypropionic acids were observed in increased amounts in the urine. Direct sequencing of the GRHPR gene revealed novel mutation, described for the first time in this article c.454dup (p.Thr152Asnfs*39) in homozygous form. The frequent nucleotide variants were found in AGXT2 gene. CONCLUSIONS: The study presents metabolomic and molecular-genetic findings in a patient with PH2. Mutation analysis broadens the allelic spectrum of the GRHPR gene to include a novel c.454dup mutation that causes the truncation of the GRHPR protein and loss of its two functional domains. We also evaluated whether nucleotide variants in the AGXT2 gene could influence the biochemical profile in PH2 and the overproduction of metabolites, especially in ketosis. We suppose that some metabolomic changes might be explained by the inhibition of the MMSADH enzyme by metabolites that increase as a consequence of GRHPR and AGXT2 enzyme deficiency. Several facts support an assumption that catabolic conditions in our patient could worsen the degree of hyperoxaluria and glyceric aciduria as a consequence of the elevated production of free amino acids and their intermediary products.