Research progress on hereditary endocrine and metabolic diseases associated with sensorineural hearing loss / 临床耳鼻咽喉头颈外科杂志

Hereditary endocrine and metabolic diseases , caused by genetic factors, exhibit complex and diverse symptoms, including the possibility of concurrent sensorineural deafness. Currently, there is a limited clinical understanding of hereditary endocrine and metabolic diseases that manifest with deafness, the pathogenesis remains unclear,and there is a lack of effective diagnostic and treatment methods. This article summarizes the research progress of hereditary endocrine and metabolic diseases complicated with deafness from the pathogenesis, clinical phenotype, diagnosis and treatment. Understanding the current research progress and integrating genetic analysis into clinical practice are crucial for accurate diagnosis and treatment, evaluating clinical efficacy, and providing effective genetic counseling for these diseases.

Disease spectrum and pathogenic genes of inherited metabolic disorder in Gansu Province of China / 中国当代儿科杂志

OBJECTIVES@#To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder (IMD) among neonates in Gansu Province of China.@*METHODS@#A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021. A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination.@*RESULTS@#A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates, and the overall prevalence rate of IMD was 0.63 (1/1 593), among which phenylketonuria showed the highest prevalence rate of 0.32 (1/3 083), followed by methylmalonic acidemia (0.11, 1/8 959) and tetrahydrobiopterin deficiency (0.06, 1/15 927). In this study, 166 variants were identified in the 28 pathogenic genes, with 13 novel variants found in 9 genes. According to American College of Medical Genetics and Genomics guidelines, 5 novel variants were classified as pathogenic variants, 7 were classified as likely pathogenic variants, and 1 was classified as the variant of uncertain significance.@*CONCLUSIONS@#This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.

Advances in research on the clinical phenotype and genetic etiology of jaundice associated with Hereditary bilirubin metabolic disorders / 中华医学遗传学杂志

Hereditary bilirubin metabolic disorder is an important cause for jaundice. For its diverse types and similar clinical manifestations, it has been difficult to make a clear etiological diagnosis. The application of next generation sequencing in recent years has delineated the more and more genetic etiologies for jaundice. This article has reviewed the clinical manifestations and genetic etiology of bilirubin metabolic disorder jaundice, with an aim to enhance the understanding of such diseases and facilitate their clinical diagnosis and treatment, which will provide a reference for genetic counseling and/or prenatal diagnosis for the affected individuals and families.

Pre-conception carrier screening for 21 inherited metabolic diseases in a Chinese population / 中华医学遗传学杂志

OBJECTIVE@#To determine the carrier rate for 21 inherited metabolic diseases among a Chinese population of childbearing age.@*METHODS@#A total of 897 unrelated healthy individuals (including 143 couples) were recruited, and DNA was extracted from their peripheral blood samples. Whole exome sequencing (WES) was carried out to screen potential variants among 54 genes associated with 21 inherited metabolic diseases. Pathogenic and likely pathogenic variants and unreported loss-of-function variants were analyzed.@*RESULTS@#One hundred fourty types of pathogenic/likely pathogenic variants (with an overall number of 183) and unreported loss-of-function variants were detected, which yield a frequency of 0.20 per capita. A husband and wife were both found to carry pathogenic variants of the SLC25A13 gene and have given birth to a healthy baby with the aid of preimplantation genetic diagnosis. The detected variants have involved 40 genes, with the most common ones including ATP7B, SLC25A13, PAH, CBS and MMACHC. Based on the Hardy-Weinberg equilibrium, the incidence of the 21 inherited metabolic diseases in the population was approximately 1/1100, with the five diseases with higher incidence including citrullinemia, methylmalonic acidemia, Wilson disease, glycogen storage disease, and phenylketonuria.@*CONCLUSION@#This study has preliminarily determined the carrier rate and incidence of 21 inherited metabolic diseases among a Chinese population of childbearing age, which has provided valuable information for the design of neonatal screening program for inherited metabolic diseases. Pre-conception carrier screening can provide an important measure for the prevention of transmission of Mendelian disorders in the population.

CHILD syndrome: successful treatment of skin lesions with topical lovastatin and cholesterol lotion

Abstract: CHILD syndrome (Congenital Hemidysplasia, Ichthyosiform erythroderma, Limb Defects) is a rare X-linked dominant disease. The authors report a 2-month-old patient presenting with typical features of CHILD syndrome that was treated with a topical solution containing cholesterol and lovastatin, with complete clearance of her CHILD nevus. The changes in skin lipid metabolism that explain the CHILD ichthyosiform nevus and their correction through topical application of cholesterol and lovastatin are discussed.

Genetic and Biochemical Consequences of Adenosine Deaminase Deficiency in Humans.

Adenosine deaminase deficiency accounts for ~15-20% of severe combined immunodeficiency in humans. The gene for adenosine deaminase is located on chromosome 20q12-q13.11 and codes for an aminohydrolase that catalyzes the deamination of adenosine and deoxyadenosine to inosine and deoxyinosine, respectively. Absence of the enzyme causes a build-up of the substrates in addition to excess deoxyadenosine triphosphate, thereby compromising the regenerative capacity of the immune system. Due to underlying allelic heterogeneity, the disorder manifests as a spectrum, ranging from neonatal onset severe combined immunodeficiency to apparently normal partial adenosine deaminase deficiency. Tandem mass spectrometry coupled with high efficiency separation systems enables postnatal diagnosis of the disorder, while prenatal diagnosis relies on assaying enzyme activity in cultured amniotic fibroblasts or chorionic villi sampling. Screening of adenosine deaminase deficiency for relatives-at-risk may reduce costs of treatment and ensure timely medical intervention as applicable. This article reviews the genetic, biochemical and clinical aspects of adenosine deaminase deficiency.

[Two sister, two paget, two metabolic disease]

Paget bone disease is a metabolic disease with unknown pathogenesis. We report the observation of two sisters with Paget disease, having a dyslipidemia past and one of them had diabetes mellitus. They both presented headache, vertigo and skull deformation. Paget bone disease diagnosis was held on phosphatase alkaline increase and radiologic investigations. Across these observations we remind clinical signs and diagnosis management of Paget disease. We discuss one etiology of this pathology, that may be genetic. Association of Paget disease and diabetes mellitus has been reported in one case

Telomere shortening & metabolic/vascular diseases.

Telomeres are specialized DNA-protein structures located at the ends of eukaryotic chromosomes whose length is progressively reduced in most somatic cells during ageing. Over the past decade, emerging evidence has shown that the telomeres are essential regulators of cellular life span and chromosome integrity in a dynamic fashion. By inducing genomic instability, replicative senescence and apoptosis, shortening of telomeres is thought to contribute to organismal ageing. While the aetiology of cardiovascular diseases and diabetes represent a complex interaction between various risk factors overlaid on different genetic backgrounds, the conventional risk factors often did not explain the inter-individual variability related to predisposition of disease states. This underscores the need for biological indicators of ageing in evaluating the aetiology of several age-related disorders, and recent studies indicate that telomere length could qualify as an ideal marker of biological ageing. Short telomeres have been detected in senescent endothelial cells and vascular smooth muscle cells from human atherosclerotic plaque as well as in myocardial tissue from patients with end-stage heart failure and cardiac hypertrophy. In addition, telomere shortening has been demonstrated in WBCs from patients with coronary heart disease, premature myocardial infarction, hypertension and diabetes mellitus. In this review, we discuss the telomere hypothesis of ageing as well as human studies that address the role of telomeres in cardiovascular, diabetes and other cardio-metabolic pathologies.

Efeito da suplementaçao com zinco na resistência à insulina em mulheres obesas / Effect of zinc supplementation on insulin resistance in obesity woman

A literatura tem demonstrado que a ação da insulina pode ser melhorada por um grande número de fatores dentre eles pelo zinco. Para verificar o efeito da suplementação com zinco na resistência à insulina na obesidade, foi realizado um estudo clínico de intervenção, duplo cego, controlado com placebo. Mulheres obesas tolerantes à glicose (n=56), com idade entre 25 e 45 anos, foram selecionadas aleatoriamente para o tratamento com zinco (30mg/dia por 4 semans). Ambos os grupos eram semelhantes ao início em relação à idade, IMC (36,2 ñ 2,3 kg/(m²), parâmetros lipídicos, composição corporal, ingestão calórica, concentração de insulina e leptina, resistência à insulina, concentração de zinco na dieta, plasma, urina e no eritrócito...

Early metabolic defects for developing diabetes mellitus among offspring of patients with type 2 diabetes are independent of gender

The aim of the study was to investigate if the female offspring of patients with Type 2 diabetes have more metabolic defects for developing diabetes mellitus than their male counterparts. Thirty-four offspring (10 males, 24 females) of patients with Type 2 diabetes mellitus aged 28.9 +/- 1.5 years (mean +/- SEM) underwent a standard oral glucose tolerance tests (OGTT; 75 g glucose in 300 ml water). Anthropometric indices, plasma lipids and blood pressure were measured while insulin resistance (IR) and sensitivity (S) were assessed using the Homeostasis Model Assessment (HOMA) method. All the offspring had normal glucose tolerance but high HOMA-derived IR values (27.2 +/- 4.2 vs. 22.5 +/- 2.7 pmol/mmol/l, p > 0.05) and low S (48.1 +/- 5.1 vs. 50.6 +/- 3.9, p > 0.05), all of which did not differ on gender comparisons. Multiple linear regression analyses suggest that gender had no influence on the outcome of the result (p = 0.37). Again, body mass index (BMI), fasting serum insulin, plasma glucose, triglyceride, total cholesterol, HDL-cholesterol and LDL-cholesterol were all similar in both genders (p > 0.05). The results suggest that though the offspring manifested metabolic defects for developing diabetes in later life, this susceptibility is independent of gender in the population studied. Further studies with a larger sample size are warranted to confirm these findings in this population.