Molecular analysis in haemophilia is currently used in the diagnosis, treatment and prognosis of this disease. Hispanic populations in Latin America have been of interest to researchers due to the ...reportedly high prevalence of inhibitors in these patients.
To perform next-generation sequencing (NGS) in a cohort of Mexican patients with HA and HB and correlate with clinical phenotypes.
Patients with Haemophilia A (HA) or haemophilia B (HB), were evaluated using NGS with an Ion AmpliSeq Custom Panel. Odds ratios (ORs) for associations between F8 variants and inhibitors were obtained.
A total of 85 patients (60 with HA and 25 with HB) were included. Pathogenic variants in F8 were found in 93.3% of HA patients and in F9 in 96% of HB patients. Twelve novel potentially pathogenic variants were found. Inhibitors were observed in 20% of patients with severe HA. Four patients clinically diagnosed with HA were negative for F8 variants.
Overall detection rate of pathogenic variants in F8 and F9 genes was 94.6%. We identified 12 non previously reported variants and pathogenic variants in other coagulation related genes. Molecular diagnosis of HA and HB permits better options for management, assessment and genetic counseling.
Menkes disease (MD) is a rare and often lethal X-linked recessive syndrome, characterized by generalized alterations in copper transport and metabolism, linked to mutations in the ATPase copper ...transporting α (ATP7A) gene. Our objective was to identify genomic alterations and circulating proteomic profiles related to MD assessing their potential roles in the clinical features of the disease. We describe the case of a male patient of 8 months of age with silvery hair, tan skin color, hypotonia, alterations in neurodevelopment, presence of seizures, and low values of plasma ceruloplasmin. Trio-whole-exome sequencing (Trio-WES) analysis, plasma proteome screening, and blood cell migration assays were carried out. Trio-WES revealed a hemizygous change c.4190C > T (p.S1397F) in exon 22 of the ATP7A gene. Compared with his parents and with child controls, 11 plasma proteins were upregulated and 59 downregulated in the patient. According to their biological processes, 42 (71.2%) of downregulated proteins had a participation in cellular transport. The immune system process was represented by 35 (59.3%) downregulated proteins (p = 9.44 × 10−11). Additional studies are necessary to validate these findings as hallmarks of MD.
Abstract Objectives We aimed to characterise baseline disease and treatment burden in a large population with haemophilia A/B, both with (HAwI/HBwI) and without (HA/HB) inhibitors. Methods The ...prospective, non‐interventional explorer6 study included patients ≥12 years old with severe HA, severe/moderate HB or HAwI/HBwI of any severity, treated according to local standard of care (excluding previous/current exposure to concizumab or emicizumab). Baseline characteristics and historical clinical data were collected and patient‐reported outcomes, including treatment burden, were assessed. Results The explorer6 study enrolled 231 patients with haemophilia (84 HAwI/HBwI) from 33 countries. At baseline, patients with HA/HB treated with prophylaxis had the lowest median annualised bleeding rates (ABRs; 2.0), irrespective of haemophilia type; of these patients, 27.5% (HA) and 31.4% (HB) had target joints. Patients with HAwI/HBwI treated episodically reported the highest treatment burden. Of these patients, 28.5% (HAwI) and 25.1% (HBwI) performed sports activities in the month before screening. Conclusion Despite receiving routine clinical care, historical and baseline information from patients enrolled in explorer6 showed that patients with HA/HB treated episodically and patients with HAwI/HBwI had higher ABRs, higher treatment burden and participated in sports less than those with HA/HB treated with prophylaxis. Emerging treatments could be beneficial in addressing these unmet medical needs.
Background
Psoriasis is strongly associated with insulin resistance (IR). Lipid profile disturbances and upregulation of enzymes crucial for fatty acid oxidation have been reported in patients with ...psoriasis. Mitochondrial ß‐oxidation is altered in patients with IR. Common mitochondrial dysfunction may be involved in the origin of both diseases.
Objective
This study aimed to evaluate mitochondrial ß‐oxidation, intermediary metabolism, and mitochondrial content in psoriatic patients with or without IR and compare them to healthy controls.
Methods
The participants were divided into three groups: (1) psoriasis and IR (n = 26); (2) psoriasis without IR (n = 17); and (3) healthy controls (n = 17). Quantification of amino acids and acylcarnitines (AC) by tandem mass spectrometry, determination of urinary organic acids by gas chromatography/mass spectrometry (GC/MS), and mitochondrial DNA quantification were performed in all groups.
Results
When comparisons were made between the two psoriatic groups, no differences were found between: C5DC + C6OH, C16:1, Met/Leu, Met/Phe, C16:1/C16, and C5DC + C6OH/C4DC + C5OH ratios. Nine analytes were different: phenylalanine, Cit/Phe, and Cit/Tyr ratios, C0, C3, C5, C6DC, C16, and C18:1OH. There were no correlations between psoriasis area and severity index (PASI), body mass index (BMI) and duration of disease with ACs. A higher proportion of patients with psoriasis showed increased urine levels of uric acid and hippuric acid (p = 0.01). The mtDNA content was significantly higher in cases than in controls, with no differences between IR and non‐IR psoriatic patients.
Conclusions
Psoriasis patients with and without IR have a different acylcarnitine profile reflecting impaired ß‐oxidation. A distinctive profile of acylcarnitines suggests an involvement of mitochondrial function associated with an increase in stearoyl CoA desaturase (SCD) activity in psoriatic patients with and without IR.
We investigated whether likely pathogenic variants co-segregating with gastroschisis through a family-based approach using bioinformatic analyses were implicated in body wall closure. Gene Ontology ...(GO)/Panther functional enrichment and protein-protein interaction analysis by String identified several biological networks of highly connected genes in
, and
. SVS-PhoRank identified a dominant model in
(also as heterozygous de novo),
,
,
,
, and
, including a recessive model in
,
,
,
, and
. A heterozygous compound model was observed in
,
,
,
,
,
, and
. These genes were implicated in pathogenetic pathways involving the following GO related categories: xenobiotic, regulation of metabolic process, regulation of cell adhesion, regulation of gene expression, inflammatory response, regulation of vascular development, keratinization, left-right symmetry, epigenetic, ubiquitination, and regulation of protein synthesis. Multiple background modifiers interacting with disease-relevant pathways may regulate gastroschisis susceptibility. Based in our findings and considering the plausibility of the biological pattern of mechanisms and gene network modeling, we suggest that the gastroschisis developmental process may be the consequence of several well-orchestrated biological and molecular mechanisms which could be interacting with gastroschisis predispositions within the first ten weeks of development.
Glucose-6-phosphate dehydrogenase deficiency (G6PDd) is the most common enzymatic disease worldwide and the prevalence is not well established because of the lack of screening. This study aimed to ...estimate the prevalence of G6PDd in a Hispanic population from Northeast Mexico.
In this retrospective study, a database was used to analyze the G6PDd in neonates included in the expanded newborn metabolic screening of inherited metabolic disorders during a period of 4 years through the GSP Neonatal G6 kit (PerkinElmer).
Among 96,152 (48,462 male) neonates screened for G6PD enzyme activity, a total of 566 (0.58%) cases were deficient for G6PD. Of those 566 patients, 469 (82.8%) attended the second test and the other 97 (17.2%) patients were lost. Of those 469 who did attend, 384 (81.9%) neonates were deficient in the second test and 85 (18.1%) were normal. With the data collected, 384 neonates were confirmed with G6PDd, 348 (88.6%) were male and 36 (11.4%) patients were female. The calculated prevalence for this population was 0.72 cases per 100 male newborns.
The prevalence of G6PDd in the Northeastern Mexican population is high. Since migration is increasing in the United States, pediatricians should be aware of the need to search for G6PDd in newborns and the wide clinical manifestations they can present.
· The calculated prevalence of glucose-6-phosphate dehydrogenase deficiency in Northeast Mexico is 3.99 cases per 1,000 newborns.. · Glucose-6-phosphate dehydrogenase deficiency screenings should be included in all newborn metabolic screenings.. · Glucose-6-phosphate dehydrogenase deficiency is a common erythroenzymopathy that must be addressed as a public health concern. To anticipate clinical complications, target population monitoring is required..
On physical examination, we noticed the presence of deep frontal furrows, thickened upper and lower eyelids, Ota nevus on the left side of the face, prognathism, bilateral knee and ankle swelling, ...clubbing of fingers and toes and watch-glass nails Figure 2. Laboratory findings, including complete blood count, thyroid function tests and serum growth hormone levels, were normal. Patient 1 was compound heterozygous due to a duplication of the second coding base of the SLCO2A1 gene, which was detected by Sanger sequencing and confirmed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
The impact of nutritional status at diagnosis of childhood acute lymphoblastic leukemia (ALL) on survival rates was assessed in a Hispanic cohort. Children <16 years with newly diagnosed ALL-B from ...2011 to 2019 were studied. Overweight and obesity were classified by body mass index (BMI) and Z-score according to WHO and CDC criteria. BMI, weight percentiles for age and Z-Score were assessed using the WHO Anthro (0-5 years) and AnthroPlus (5-19 years) programs. Cox model was used to estimate risk factors for relapse and death; differences between groups were assessed with Student's T test for parametric and Mann-Whitney U test for non-parametric variables. Disease-free survival (DFS) and overall survival (OS) were determined by the Kaplan-Meier method, calculating time, status, cumulative survival and standard error with a 95% confidence interval. Equal data distribution was estimated with the log-rank test. One-hundred and seventy-two B-ALL children were studied. The overweight-obese group had a non-significant lower DFS (CDC: 54% vs. 60%, p = 0.80; WHO: 57% vs. 64%, p = 0.89) and OS rate (CDC:76% vs. 82%, p = 0.38; WHO:65% vs. 81%, p = 0.13). An association between nutritional status determined by CDC and WHO criteria at diagnosis of B-cell ALL and survival rates was not documented.
Sticky Platelet Syndrome (SPS) is a disorder characterized by platelet hyperaggregability, diagnosed by studying in vitro platelet aggregation with ADP and epinephrine. It is the second most common ...cause of thrombophilia in Mexican Mestizos and manifests as an autosomal dominant trait which, combined with other coagulopathies, contributes significantly to the morbidity and mortality of patients with primary thrombophilia. It is easily treatable with antiplatelet drugs; however, the methods for diagnosis are not readily available in all clinical laboratories and the disorder is often overlooked by most clinicians. Herein, we present the results of more than 20 years of Mexican experience with the study of SPS in a Mestizo population.
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