According to epidemiological studies, constipation has a negative effect on life expectancy, necessitating appropriate treatment. According to the Pharmaceuticals and Medical Devices Agency (PMDA), patients who have been taking magnesium oxide (MgO) for constipation over a prolonged period, especially those with impaired renal function and older individuals, are at high risk of hypermagnesemia. Therefore, serum Mg levels, which are often not checked in clinical practice, should be monitored in these patients. Thus, to predict elevated serum Mg levels and prevent the development of hypermagnesemia, we aimed to identify the risk factors of hypermagnesemia, especially in the older population. Our study included patients who were prescribed MgO at our hospital between January 1, 2014, and March 31, 2016. Patients who did not meet the inclusion criteria were excluded and matched to adjust for background factors; finally, 35 patients in the hypermagnesemia arm and 140 patients in the non-hypermagnesemia arm were included in the analysis. Multivariate analysis identified estimated creatinine clearance (eCcr) ≤ 28.2 mL/min as a statistically significant risk factor. In addition, MgO dose ≥ 900 mg/day was identified as a risk factor for clinical consideration, although not statistically significant. Furthermore, the incidence of hypermagnesemia was shown to increase to 11.6% for those with MgO dose ≥ 900 mg/day, 27.0% for those with eCcr ≤ 28.2 mL/min, and 53.1% for those with both. Hypermagnesemia may occur in older patients with eCcr ≤ 28.2 mL/min who take more than 900 mg/day of MgO.

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Mucopolysaccharidosis type VI (MPS VI), also known as Maroteaux-Lamy syndrome, polydystrophic dwarfism, and arysulfatase B (ASB) deficiency, is a lysosomal storage disorder with autosomal recessive inheritance characterized by progressive multisystem involved that causes many tissues and organs to enlarge and become inflamed. Skeletal deformities are common that progress and worsen in varying degrees thus affecting quality of life and life expectancy. Many studies have shown that allogeneic hematopoietic stem cell transplantation can reduce morbidity and enhance the survival and quality of life in such patients. We present a case of a 6-year-old girl diagnosed with MPS VI at the age of 3 years. Thereafter the patient developed various complications of the disease causing morbidity. She was then treated with combined umbilical cord blood (UCB) and bone marrow (BM) transplantation from complete human leukocyte antigen-matched (6/6) donor which was her younger sibling. The transplant was successful without any serious adverse effects. No additional treatments such as enzyme replacement therapy (ERT) were required. The transplantation of UCB along with BM can be considered as an effective treatment approach for this rare disease.
UNASSIGNED: Case of MPS VI treated with stem cell transplantation: This article reports a case of a 6-year-old girl who was diagnosed with mucopolysaccharidosis type VI also known as MPS VI, an autosomal recessive disorder that caused her arysulfatase B (ASB) deficiency. This disorder affects growth velocity, gives coarse facial features, gives rise to skeletal deformities, frequent upper-airway infections, enlarged liver and spleen, hearing loss, and joint stiffness. However, very few studies have reported definitive ways to treat or cure MPS VI. To help her combat this disorder, combined umbilical cord blood and bone marrow transplantation was done. This transplant alleviated her symptoms, and the patient did not need any further treatment. Follow-up, 4 years after transplantation, shows normal enzyme level, no complications, and improved quality of life.

Studies which analyse the joint effect of acoustic or chemical air pollution variables and different meteorological variables on neuroendocrine disease are practically nonexistent. This study therefore sought to analyse the impact of air pollutants and environmental meteorological variables on daily unscheduled admissions due to endocrine and metabolic diseases in the Madrid Region from January 01, 2013 to December 31, 2018.
We conducted a longitudinal, retrospective, ecological study of daily time series analysed by Poisson regression, with emergency neuroendocrine-disease admissions in the Madrid Region as the dependent variable. The independent variables were: mean daily concentrations of PM10, PM2.5, NO2 and O3; acoustic pollution; maximum and minimum daily temperatures; hours of sunlight; relative humidity; wind speed; and air pressure above sea level. Estimators of the statistically significant variables were used to calculate the relative risks (RRs).
A statistically significant association was found between the increase in temperatures in heat waves, RR: 1.123 95% CI (1.001-1.018), and the number of emergency admissions, making it the main risk factor. An association between a decrease in sunlight and an increase in hospital admissions, RR: 1.005 95% CI (1.002 1.008), was likewise observed. Similarly, ozone, in the form of mean daily concentrations in excess of 44 μg/m3, had an impact on admissions due to neuroendocrine disease, RR: 1.010 95% CI (1.007-1.035). The breakdown by sex showed that in the case of women, NO2 was also a risk factor, RR: 1.021 95% CI (1.007-1.035).
The results obtained in this study serve to identify risk factors for this disease, such as extreme temperatures in heat waves, O3 or NO2. The robust association found between the decrease in sunlight and increase in hospital admissions due to neuroendocrine disease serves to spotlight an environmental factor which has received scant attention in public health until now.

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UNASSIGNED: Succinate dehydrogenase deficiency, also known as mitochondrial complex II deficiency, is a rare inborn error of metabolism, accounting for approximately 2% of mitochondrial disease. Mutations in the four genes SDHA, B, C,and D have been reported resulting in diverse clinical presentations. The vast majority of clinically affected individuals reported in the literature harbor genetic variants within the SDHA gene and present with a Leigh syndrome phenotype, clinically defined as a subacute necrotizing encephalopathy.
UNASSIGNED: Herein, we report the first case of a 7-year-old child who was diagnosed as having succinate dehydrogenase deficiency. The affected child presented at 1 year of age with encephalopathy and developmental regression following viral illnesses. MRI changes supported a clinical diagnosis of Leigh syndrome and c.1328C>Q and c.872A>C SDHA variants were identified as compound heterozygous. Mitochondrial cocktail treatment including L-carnitine, riboflavin, thiamine, biotin, and ubiquinone was started. Mild clinical improvement was observed after treatment. He is now unable to walk and speak. The second patient, a 21-year-old woman, presented with generalized muscle weakness, easy fatigability, and cardiomyopathy. Investigations revealed increased lactate level of 67.4 mg/dL (4.5-19.8) with repeatedly increased plasma alanine levels 1,272 µmol/L (200-579). We administered carnitine, coenzyme, riboflavin, and thiamine for empirical therapy with the suspicion of mitochondrial disease. Clinical exome sequencing revealed compound heterozygous variants NM_004168.4:c.1945_1946del (p.Leu649GlufsTer4) at exon 15 of the SDHA gene and NM_004168.4:c.1909-12_1909-11del at intron 14 of SDHA gene.
UNASSIGNED: There are several very different presentations including Leigh syndrome, epileptic encephalopathy, and cardiomyopathy. Some cases present following viral illness; this feature is not specific to mitochondrial complex II deficiency and occurs in many other mitochondrial disease presentations. There is no cure for complex II deficiency, though some reported patients showed clinical improvement following riboflavin therapy. Riboflavin is not the only therapeutic intervention that is available to patients with an isolated complex II deficiency and various other compounds have shown promise in the treatment of symptoms, including L-carnitine and ubiquinone. Treatment alternatives such as parabenzoquinone EPI-743 and rapamycin are under study in the treatment of the disease.

Many new drugs have been approved over the past decade for rare or orphan diseases. The passage of the Orphan Drug Act (ODA) in 1983 has provided key economic and regulatory incentives to provide medicines for patients who are suffering from rare diseases that may not be commercially attractive for research and development. We have analyzed 497 novel drugs approved from 2010 - June 13, 2022, of which 220 were given orphan designation status. We discuss trends over this time period, potential risks for long development times, and provide example case studies of successful development and launch of novel drugs for rare diseases.

BACKGROUND: Both hyperuricaemia and hyperlipidaemia are common metabolic diseases that are closely related to each other, and both are independent risk factors for the development of a variety of diseases. HUA combined with hyperlipidaemia increases the risk of nonalcoholic fatty liver disease and coronary heart disease. This study aimed to investigate the relationship between HUA and hyperlipidaemia and study the metabolic pathway changes in patients with HUA associated with hyperlipidaemia using metabolomics.
METHODS: This was a case‒control study. The prevalence of hyperlipidaemia in HUA patients in the physical examination population of Tianjin Union Medical Centre in 2018 was investigated. Metabolomics analysis was performed on 308 HUA patients and 100 normal controls using Orbitrap mass spectrometry. A further metabolomics study of 30 asymptomatic HUA patients, 30 HUA patients with hyperlipidaemia, and 30 age-and sex-matched healthy controls was conducted. Differential metabolites were obtained from the three groups by orthogonal partial least-squares discrimination analysis, and relevant metabolic pathways changes were analysed using MetaboAnalyst 5.0 software.
RESULTS: The prevalence of hyperlipidaemia in HUA patients was 69.3%. Metabolomic analysis found that compared with the control group, 33 differential metabolites, including arachidonic acid, alanine, aspartate, phenylalanine and tyrosine, were identified in asymptomatic HUA patients. Pathway analysis showed that these changes were mainly related to 3 metabolic pathways, including the alanine, aspartate and glutamate metabolism pathway. Thirty-eight differential metabolites, including linoleic acid, serine, glutamate, and tyrosine, were identified in HUA patients with hyperlipidaemia. Pathway analysis showed that they were mainly related to 7 metabolic pathways, including the linoleic acid metabolism pathway, phenylalanine, tyrosine and tryptophan biosynthesis pathway, and glycine, serine and threonine metabolism pathway.
CONCLUSIONS: Compared to the general population, the HUA population had a higher incidence of hyperlipidaemia. HUA can cause hyperlipidaemia. by affecting the metabolic pathways of linoleic acid metabolism and alanine, aspartate and glutamate metabolism. Fatty liver is closely associated with changes in the biosynthesis pathway of pahenylalanine, tyrosine, and tryptophan in HUA patients with hyperlipidaemia. Changes in the glycine, serine and threonine metabolism pathway in HUA patients with hyperlipidaemia may lead to chronic kidney disease.

BACKGROUND: As a gram-negative and microaerophilic bacterium, Helicobacter pylori (HP) is the main cause of chronic gastritis. Therefore, considering the high prevalence of HP infection worldwide, as well as the increasing prevalence of metabolic disorders, the present study aimed to investigate the relationship between HP infection eradication and metabolic profile.
METHODS: This prospective case-control study was performed on patients with HP infection whom referred to 7 medical centers in 3 countries (Iran, Egypt, and Vietnam) in 2020-2021. The metabolic profile of all of the participants evaluated before starting of treatment for HP eradication and 3 months after the treatment. Then changes of metabolic profile compared between those with successful HP eradication (group A) and subjects who failed to eradicate (group B).
RESULTS: Overall, 199 patients, including 93 male (46.7%) with the mean age of 44.5 years (18-93 years) included. Based on response to treatment, the participants allocate into group A (those who respond to HP eradication): 164 cases (82.42%); or group B as those who failed to achieve eradication (35 cases, 17.58%). Racially 86.9% of participants were Caucasian and 89% diagnosed as non-ulcer dyspepsia (NUD). The most prevalent comorbidity include hypertension (11.5%) and hyperlipidemia (10%) which were more prevalent in group B (P = 0.002). Three months after therapy, average weight of participants among those who achieved eradication (group A) decreased from 73.1 to 71.4 kg (P = 0.01), but in comparison with group B, was non-significant (P = 0.171). The BMI of patients before and after treatment did not show any significant differences. The biochemical parameters of patients before and after treatment were not significantly different regardless of treatment success (P > 0.05). The levels of total cholesterol and VLDL cholesterol after treatment were not significantly different from baseline values in two groups. HDL and LDL cholesterol levels before and after treatment in the resistant group were significantly higher than the responding group. Average serum TG level decreased significantly after treatment in the group A (P < 0.0001), in contrast to the resistant group (P = 0.356). The liver transaminases (AST and ALT) before and after treatment were not significantly different between the two groups (P > 0.05). The results of logistic regression showed that the eradication of infection has no significant affect any of the metabolic profile parameters.
CONCLUSIONS: HP infection treatment in individuals without significant metabolic disorders does not affect metabolic parameters up to 3 months after eradication. HP eradication among subjects with several comorbidities mandates eradication protocol intensification to avoid treatment failure.

BACKGROUND: 17α-hydroxylase deficiency (17OHD) is a rare autosomal recessive disorder. Aldosterone levels are usually low in patients with 17OHD. However, among the approximately 150 cases of 17OHD reported to date, aldosterone levels were not low in all cases. Therefore, some 17OHD cases may have been misdiagnosed as primary aldosteronism (PA) cases. Often before puberty, 17OHD is diagnosed because of abnormal genital morphology and menstrual irregularities. However, we report a very rare case of 17OHD in an elderly patient with a high aldosterone/renin ratio (ARR) similar to that in PA.
METHODS: A 63-year-old Japanese woman was transferred to our medical facility for the evaluation of bilateral adrenal hypertrophy, which was incidentally discovered during an abdominal examination after cholecystectomy. The patient had hypokalemia and a high aldosterone/renin ratio. Her medical history included hypertension and right intracerebral capsular hemorrhage at the age of 30 years. Additional testing revealed low cortisol, high adrenocorticotropic hormone, and low testosterone and dehydroepiandrosterone sulfate, indicating congenital adrenal hyperplasia. Genetic analysis revealed a mutation in the CYP17A1 gene and a karyotype of 46, XY; hence, she was diagnosed with 17OHD.
CONCLUSIONS: 17OHD can resemble PA. The combination of a high ARR and low cortisol level should trigger the consideration of 17OHD.