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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a loss of motor neurons in the brain and spinal cord, leading to progressive muscle weakness in multiple regions of the body. No effective treatment is available and the disease progresses rapidly to death with an average survival time of 3-5 years after symptom onset. The etiology of ALS is unknown for the majority of the patients. Alterations in the carbohydrate and lipid metabolisms, together with hypermetabolism, are features of ALS patients that are not yet well characterized. Understanding the early metabolic symptoms of the disease might be a necessary step for the identification of an effective treatment. Paper I describes a nested case-control study on the association between diabetes and the future risk of ALS in the Swedish population. A total of 5,108 new ALS cases among the Swedish residents between 1991 and 2010 were identified from the National Patient Register. Through linkages to several nationwide Swedish registers five controls per case were selected from the entire Swedish population using incidence density sampling and diabetes diagnoses were identified for both cases and controls from hospital admission records, outpatient care records, prescription of antidiabetics, or a combination of the three. An overall inverse association between diabetes and risk of ALS was found. There was however a positive association between insulin-dependent diabetes before age 30 and ALS risk. Paper II describes the association between body mass index (BMI), BMI change and ALS risk and survival in the GENEVA study, a case-control study of United States military veterans. Self-reported BMI at age 25, 40 and at time of ALS diagnosis (interview for controls) was compared. Low BMI at age 40 was associated with increased risk of developing ALS and the association was stronger for cases with diagnostic delay shorter than one year. Stable or decreasing BMI between age 25 and 40 was also associated with higher risk of ALS compared to an increasing BMI. However, premorbid BMI and BMI change did not predict survival of ALS patients. Paper III describes the association between ALS risk and serum glucose, total cholesterol, LDL-C, HDL-C, triglycerides, apolipoprotein B (apoB), and apolipoprotein A-I (apoA-I) in a Swedish populationbased cohort study. High LDL-C, apoB and the LDL-C/HDL-C and apoB/apoA-I ratios were associated with a higher incidence of ALS. These associations seemed to be mainly due to a strong association of apoB with ALS risk. High glucose level ( 6.11 mmol/L) was associated with a lower incidence of ALS. During the 10 years before diagnosis, ALS patients had increasing levels of LDL-C, HDL-C, apoB and apoA-I, whereas gradually decreasing levels of LDL-C/HDL-C and apoB/apoA-I ratios. Paper IV describes a population-based nested case-control study of 2,475 Swedish residents diagnosed with ALS during July 2006-December 2013, and 12,375 population controls. Information on filled prescriptions of antidiabetics and statins were extracted from the Swedish Prescribed Drug Register. Antidiabetics were associated with a lower ALS risk, the association was stronger for men, for individuals above age 65, and for ALS with longer disease duration. Statins were not associated with ALS risk overall, though a positive association was noted among women. The latter association was mostly explained by increased statins use during the year before ALS diagnosis. The studies presented in this thesis have taken advantage of different study designs and populations to systematically investigate the relationship between metabolic disorders and ALS risk and, to a lesser extent, progression. Therefore, they contributed substantially to fill the knowledge gap about the association between metabolic disorders and neurodegeneration in ALS. Furthermore, Paper I and Paper IV serve as excellent examples of the unique possibilities offered by the nationwide health registers in Sweden that can, when equipped with modern analytical methods, contribute to the understanding of complex diseases.

Inborn errors of metabolism are inherited biochemical disorders caused by lack of a functional enzyme, transmembrane transporter, or similar protein, which then results in blockage of the corresponding metabolic pathway. Taken individually, inborn errors of metabolism are rare. However, as a group these diseases are relatively frequent and they may account for most of neonatal mortality and need of health resources. The detection of genetic metabolic disorders should occur in a pre-symptomatic phase. Recently, the introduction of the tandem mass spectrometric methods for metabolite analysis has changed our ability to detect intermediates of metabolism in smaller samples and provides the means to detect a large number of metabolic disorders in a single analytical run. Screening panels now include a large number of disorders that may not meet all the criteria that have been used as a reference for years. The rationale behind inclusion or exclusion of a respective disorder is difficult to understand in most cases and it may impose an ethical dilemma. The current organization is an important tool of secondary preventive medicine, essential for children's healthcare, but the strong inhomogeneity of the regional models of screening applied today create in the Italian neonatal population macroscopic differences with regards to healthcare, which is in effect mainly diversified by the newborn's place of birth, in possible violation of the universal criterion of the equality of all citizens. Carefully weighed arguments are urgently needed since patient organizations, opinion leaders and politicians are pressing to proceed with expansion of neonatal population screening.

IntroductionMorphological and metabolic complications in HIV patients on antiretroviral therapy remain a challenge. While new cases of lipoatrophy (LA) disappear, irreducible central lipohypertrophy (LH) and metabolic complications require highly specialized management. We described a day hospital dedicated to lipodystrophy (LD) and metabolic disorders in HIV patients on treatment in Geneva, Switzerland, with a focus on LH.Materials and MethodsThe "Groupe Lipo & Metabolism" is a multidisciplinary consultation where patients undergo a standard evaluation including questionnaire, physical examination, dual‐energy x‐ray absorptiometry (DEXA) and L5‐level CT scans, blood tests and consultations with various specialists. Based on prospectively maintained data, we describe clinical, biological and radiological characteristics of patients ≥18 years who attended the consultation between 2008 and 2013. We defined LH by CT scan, the gold standard method, as abdominal visceral adipose tissue (VAT) ≥130 cm2, value associated with increased risk of cardiovascular event.ResultsA total of 195 patients attended the consultation during study period. Reasons for referral included LH in 28.3%, LA in 25% and mixed syndrome in 15.5% of cases. Metabolic disorders accounted for 19% of referrals with or without LD features. Among patients with a CT scan performed (n=183), 46 (25%) had LH with a VAT ≥130 cm2. In this population, mean age was 49.1 years and 53.6% were male. HIV viral load was <50 cp/ml in 87% of patients. Mean body mass index was 24.6 kg/m2. Mean waist to hip ratio (WHR) was 0.98 for males and 0.89 for females. A total of 9.8%, 29.5% and 35% of patients had abnormal levels of total cholesterol (≥6.5 mmol/L), triglycerides (≥2.0 mmol/L) and HDL cholesterol (≤1.0 mmol/L), respectively. Mean fasting glycaemia was 5.7 mmol/L and HbA1c was >6% in 10.5% of patients. Vitamin‐D level was <75 nmol/L in 70.7% of patients. Respectively 31.2% and 12.1% of patients had osteopenia and osteoporosis on the spine and 44.8% and 6.6% on the hip neck. Factors associated with a VAT≥130 cm2 included male gender (OR 3.7 [95% CI 1.7–8.2] p<0.001), triglycerides ≥2 mmol/L (OR 2.6 [95% CI 1.3–5.4] P<0.01) and increase in BMI category (OR 1.8 [95% CI 1.2–2.8] p<0.01).ConclusionsLipohypertrophy is a prevalent feature of fat redistribution among HIV patients on treatment. Risk factors for LH include male gender, dyslipidemia and overweight. Glucose impairment and bone disorders are also common. A multidisciplinary approach is important to identify and promptly address these disorders.AcknowledgmentsThe "Groupe Lipo & Metabolism" team.

Inherited metabolic disorders (IMDs) are mostly rare, have overlapping symptoms, and can be devastating and progressive. However, in many disorders, early intervention can improve long-term outcomes, and newborn screening (NBS) programmes can reduce caregiver stress in the journey to diagnosis and allow patients to receive early, and potentially pre-symptomatic, treatment. Across Europe there are vast discrepancies in the number of IMDs that are screened for and there is an imminent opportunity to accelerate the expansion of evidence-based screening programmes and reduce the disparities in screening programmes across Europe. A comprehensive list of IMDs was created for analysis. A novel NBS evaluation algorithm, described by Burlina et al. in 2021, was used to assess and prioritise IMDs for inclusion on expanded NBS programmes across Europe. Forty-eight IMDs, of which twenty-one were lysosomal storage disorders (LSDs), were identified and assessed with the novel NBS evaluation algorithm. Thirty-five disorders most strongly fulfil the Wilson and Jungner classic screening principles and should be considered for inclusion in NBS programmes across Europe. The recommended disorders should be evaluated at the national level to assess the economic, societal, and political aspects of potential screening programmes.

Objective. Birth defects are among the leading causes of infant mortality and morbidity in the Philippines. While affected infants make up a sizeable portion of live births in General Santos City (GSC), no information is available about their actual numbers. This study aims to fill the knowledge gap about the prevalence and nature of congenital anomalies (CAs) and congenital metabolic disorders (CMDs) in the city from 2009 to 2012. Methods. A retrospective study of in-patient records from six (6) medical facilities was done for CA/CMD cases from 2009-2012. Among the CMDs tested were congenital hypothyroidism (CH), congenital adrenal hyperplasia (CAH), galactosemia (GAL), hyperphenyalaninemia (HPA), phenylketonuria (PKU) and glucose-6-phosphate dehydrogenase deficiency (G6PD def). Results. Collected data revealed 109 cases of CAs with limb deformities, oro-facial clefting and neural tube disorders comprising majority of cases. There were 878 reported cases of CMDs with glucose-6-phosphate dehydrogenase deficiency (G6PD def) as the most prevalent at 829 cases. There was also a preponderance of CAs/CMDs in a government hospital for the indigent. Conclusions. These results underscore the emergence of CAs and CMDs as a major health problem among newborns in GSC. Higher incidences of birth defects in one district hospital also reveal a tentative link between CA/CMD incidence and socioeconomic status. It is of paramount importance therefore, to undertake expansion of the newborn screening program and to establish local birth registries so that a more comprehensive and realistic picture of CA/CMD prevalence in the city will be obtained.

Overcoming nutritional problems including stunting in Indonesia has been carried out through various programs launched by the government. However, problem of stunting in infants is still high at 35.6% compared to the MDGS target of 15%. Adequat of macro and micro nutrient intake is an important element in overcoming the problem of stunting. The amino acid cysteine is one of the amino acids that can help the process of accelerating growth. In the growth process, the amino acid cysteine has a role in accelerating the transcription of hormone receptors in the reaction of zinc finger protein (ZFP), induction of Transforming Growth Factor β (TGF β) and the formation of CRIP (Cystein Rich Intestinal Protein) which are strongly associated with advanced metabolic reactions in forming energy for growth.The pre-post randomizet design control study was conducted in two sample groups, control and treatment. A total of 30 stunting toddlers. The treatment group was given 25 mg of cysteine amino acid / day with the time of administration for 3 months or 90 times. Indicator of metabolic disorders using the urinalysis method to analyze urine protein content, intake level was measured using a 24-hour Food Recall and anthropometric measurements which Body Weight and Height. Results of the study showed that giving amino acid cysteine could not improve metabolic disorders in stunting infants with indicaor urinalysis. The level of macro and micro nutrient intake is not in accordance with the needs of toddlers. There was a significant change in anthropometric status in the treatment group. Suggestions for further research should be to measure indicators of improvement in metabolic disorders with more accurate blood specimens. Keywords: Cysteine Amino Acid, Height, Intake of Nutrition, Stunting Urinalysis, Weight.