Genetics
Stephan Strobel, Lewis Spitz, Stephen D. Marks in Great Ormond Street Handbook of Paediatrics, 2019
Classical Rett syndrome affects females. There is apparent normal early development followed by a period of developmental regression in terms of language and motor skills at between 6 and 18 months of age. Subsequently, speech is typically absent and development remains severely delayed in all areas (Fig. 15.24). Stereotypic midline hand movements are common, replacing purposeful hand movements. Head growth decelerates. Occasionally males are observed with MECP2 mutations. They manifest with a severe neonatal encephalopathy. Diagnosis: mutation analysis of the MECP2 gene.Inheritance: X-linked dominant with almost all mutations occurring de novo.Differential diagnosis: see Table 12; metabolic disorders.
Cerebral Palsy
Merlin G. Butler, F. John Meaney in Genetics of Developmental Disabilities, 2019
Laboratory tests that are often of value in the evaluation of CP include a head CT scan or MRI and might show dilated ventricles indicative of poor brain growth or atrophy and periventricular leukomalacia. If the arms are completel y spared, imaging of the cervical cord and spine is indicated to rule out a cord lesion. If the cause is suspected to be a metabolic disorder, a genetic evaluation should be undertaken. A variety of appropriate tests to assess the myriad of associated findings or comorbidities are mandatory to insure that they are discovered early and treatments instigated. Of special concern are evaluations of sensory function such as hearing and vision. Problems are frequently found in these areas, and treatments must be started early to insure that the child’s potential is not further compromised.
Basic genetics and patterns of inheritance
Hung N. Winn, Frank A. Chervenak, Roberto Romero in Clinical Maternal-Fetal Medicine Online, 2021
One of the most common metabolic disorders is the autosomal recessive aminoacidopathy phenylketonuria (PKU), which has an incidence of 1 in 10,000 to 1 in 15,000 newborns (38). It is caused by a deficiency of the enzyme phenylalanine hydroxylase, which normally converts phenylalanine to tyrosine. Patients with PKU have elevated blood levels of phenylalanine and excretion of phenylketones in the urine. If left untreated, affected individuals will develop microcephaly and profound mental retardation due to the toxic effects of the elevated compounds. However, if diagnosed within the first few weeks of life, with institution of a low phenylalanine diet, mental retardation can be prevented. PKU is the first genetic disorder for which there has been generalized population screening. Since the 1960s, all newborns in the United States have been tested for the disorder. This has nearly eliminated PKU as a cause for mental retardation. However, a new problem has emerged; women who were allowed to stop the dietary restriction of phenylalanine after age 6 years are now of childbearing age. The elevated blood level of phenylalanine in a pregnant PKU woman has deleterious effects on the developing fetus, with increased risk for spontaneous pregnancy loss, congenital heart defects, severe microcephaly, and mental retardation. Therefore, the PKU diet must be reinstituted prior to conception and continued throughout pregnancy. New guidelines state that all people with PKU should remain on the diet for life.
Comorbidity patterns among people living with HIV: a hierarchical clustering approach through integrated electronic health records data in South Carolina
Published in AIDS Care, 2021
Xueying Yang, Jiajia Zhang, Shujie Chen, Sharon Weissman, Bankole Olatosi, Xiaoming Li
The hierarchical cluster analysis identified four comorbidity clusters from the 24 diagnosis groups. As shown in Figure 2, the four comorbidity clusters were: (1) “substance use and mental disorders” (6 diagnosis groups: alcohol use, tobacco use, anxiety, depression, psychiatric disorders, illicit drug use); (2) “metabolic disorders” (10 diagnosis groups: hypothyroidism, anemia, diabetes, dyslipidemia, cardiac disorders, hypertension, ulcer disease, chronic obstructive pulmonary disease [COPD], osteoporosis/osteoarthritis, chronic kidney disease); (3) “liver disease and cancer” (4 diagnosis groups: hepatitis B, chronic liver disease, hepatitis C, non-AIDS defining cancers); and (4) “cerebrovascular disease” (4 diagnosis groups: stroke, cerebral infarction, peripheral vascular disease, dementia). The concurrence (in %) of comorbidity clusters among all the PLWH were shown in Figure 3, with 11.50% of the patients being diagnosed only with substance use and mental disorders (cluster 1), 12.94% only with metabolic disorders (cluster 2), 0.52% only with liver diseases and cancer (cluster 3) and 0.09% only with cerebrovascular disease (cluster 4). In the meantime, the 2 most frequent concurrent dyads were: clusters 1 and 2 (22.56%) and clusters 2 and 3 (1.30%). The 2 most frequent concurrent triads were clusters 1, 2, and 3 (6.22%) and clusters 1, 2, and 4 (2.41%). The proportion of patients who were diagnosed with all four clusters was low (1.32%).
Exciting advances in GPCR-based drugs discovery for treating metabolic disease and future perspectives
Published in Expert Opinion on Drug Discovery, 2019
Mar Quiñones, Johan Fernø, Carlos Diéguez, Ruben Nogueiras, Omar Al-Massadi
Metabolic disorders comprise an array of genetically or acquired diseases, such as obesity, anorexia, diabetes, heart or liver disease that all involve disruption of the metabolic machinery involved in energy balance control. Based on recent estimates, worldwide obesity has doubled since 1975 and life expectancy in modern societies is beginning to decline due to the ever-rising prevalence of obesity and diabetes [1]. Currently, the most effective approach to obtain a sustained decrease in body weight and improved insulin sensitivity is bariatric surgery [2,3]. However, this type of intervention is highly invasive, irreversible, costly and not without considerable risk for the patient, and thus cannot be a general recommendation for the treatment of obesity [4]. Pharmacological treatment is another option, and several anti-obesity drugs have been approved by the Food and Drug Administration (FDA) and/or the European Medicines Agency (EMA), but their efficacy and/or safety is overall still suboptimal [5].
Cost-effectiveness of baloxavir marboxil compared with laninamivir for the treatment of influenza in patients at high risk for complications in Japan
Published in Current Medical Research and Opinion, 2021
Mariia Dronova, Hidetoshi Ikeoka, Naoya Itsumura, Nobuo Hirotsu, Amir Ansaripour, Samuel Aballéa, Yoshie Onishi, Mark Hill, Ataru Igarashi
The following list of HRC was considered in line with the Centers for Disease Control and Prevention’s definition and phase III clinical trial of baloxavir3,8:Asthma or chronic lung disease.Endocrine disorders.Compromised immune system.Neurological and neurodevelopmental disorders.Heart disease (excluding hypertension).Blood disorders.Metabolic disorders.Morbid obesity.Women within 2 weeks postpartum – for patients aged <65 years only.Residents of long-term care facilities – for patients aged ≥65 years only.
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