BACKGROUND: Sudden Unexplained Death in Childhood (SUDC) needs to be fully assessed considering its impact on the family, parents and siblings. Inborn Errors of Metabolism (IEM) such as Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD) should be taken into consideration when SUDC occurres. Our aim is to present a family with two successive SUDC and to discuss the post-mortem genetics investigations revealing an IEM implication.
METHODS: A complete autopsy with genetic testing was performed when the proband, a 4-year-old girl, died. A few years previously, her older brother had died at the same age and off the same condition. Years later, his exhumation was necessary in order to perform a post-mortem diagnosis.The two siblings were revealed to have had the same pathogenic genotype of the ACADM gene, heterozygous substitutions in ACADM (NM_000016.5): c.985 A>G p.(Lys329Glu) and c.347 G>A p.(Cys116Tyr). In addition, they also both carried a VUS in TECRL, a gene implicated in Catecholaminergic Polymorphic Tachycardia Ventricular (CPVT) and SUDC.
CONCLUSIONS: We illustrate the importance of exome analyses for investigating unexplained sudden death, especially in children, with the possible impact for genetic counselling in the family. The finding of the implication of ACADM gene in this case, raises likely responsibility of the public health system in countries such as France, who delayed implementation of new born screening for these conditions. Exome analyses in this case detected unexpected complexity in interpretation linked to the identification of a second candidate gene for SUDC.

The subject of the study is an 11-month old IVF baby girl with the typical clinical manifestation of malonyl coenzyme A decarboxylase deficiency, including developmental delay, limb weakness, cardiomyopathy, and excessive excretion of malonic acid and methylmalonic acid. Whole genome sequencing (WGS) revealed a novel heterozygous nonsense mutation (c.672delG, p.Trp224Ter) in the MLYCD gene of the proband and her father and a novel heterozygous deletion in 5\'-UTR-exon1-intron1 of the MLYCD gene of the proband and her mother. The patient\'s cardiac function and limb weakness improved considerably after 3 months of a low-fat diet supplemented with L-carnitine. Furthermore, mapping of gene mutations and clinical manifestations was done by case collection.

UNASSIGNED: Obesity has emerged as one of the major risk factors of severe morbidity and cause-specific mortality among severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infected individuals. Patients with obesity also have overlapping cardiovascular diseases and diabetes, which make them increasingly vulnerable. This novel ecological study examines the impact of obesity and/or body mass index (BMI) on rates of population-adjusted cases and deaths due to coronavirus disease 2019 (COVID-19).
UNASSIGNED: Publicly available datasets were used to obtain relevant data on COVID-19, obesity and ecological variables. Group-wise comparisons and multivariate logistic regression analyses were performed. The receiver operating characteristic curve (ROC) was plotted to compute the area under the curve.
UNASSIGNED: We found that male BMI is an independent predictor of cause-specific (COVID-19) mortality, and not of the caseload per million population. Countries with obesity rates of 20-30% had a significantly higher (approximately double) number of deaths per million population to both those in < 20% and > 30% slabs. We postulate that there may be a U-shaped paradoxical relationship between obesity and COVID-19 with the cause-specific mortality burden more pronounced in the countries with 20-30% obesity rates. These findings are novel along with the methodological approach of doing ecological analyses on country-wide data from publicly available sources.
UNASSIGNED: We anticipate, in light of our findings, that appropriate targeted public health approaches or campaigns could be developed to minimize the risk and cause-specific morbidity burden due to COVID-19 in countries with nationwide obesity rates of 20-30%.

Incidence of early-onset (<50 years) colorectal cancer (EOCRC) is increasing in developed countries. The aim was to investigate autoimmune and metabolic conditions as risk factors for EOCRC. In a nationwide nested case-control study, we included all EOCRC cases in Sweden diagnosed during 2007-2016, together with controls, matched for birth year, sex, and county. Information on exposure of autoimmune or metabolic disease was collected from the National Patient Register and Prescribed Drugs Registry. Hazard ratios (HR) as measures of the association between EOCRC and the exposures were estimated using conditional logistic regression. In total, 2626 EOCRC patients and 15,756 controls were included. A history of metabolic disease nearly doubled the incidence hazard of EOCRC (HR 1.82, 95% CI 1.66-1.99). A sixfold increased incidence hazard of EOCRC (HR 5.98, 95% CI 4.78-7.48) was seen in those with inflammatory bowel disease (IBD), but the risk increment decreased in presence of concomitant metabolic disease (HR 3.65, 95% CI 2.57-5.19). Non-IBD autoimmune disease was not statistically significantly associated with EOCRC. IBD and metabolic disease are risk factors for EOCRC and should be considered in screening guidelines.

BACKGROUND: Ochronosis, also known as alkaptonuria, is a rare autosomal recessive self-metabolic disease arising from deficiency of homogentisate 1,2 dioxygenase enzyme. It affects several organs and muscoskeletal structures. We herein report a case of a patient who presented with severe hip arthropathy complicated with late stage ochronosis.
METHODS: A 56-year-old male patient was admitted in our department in 2019 with complaints of chronic low backache and left hip pain. After the required investigations were done, lumbar disc herniation and severe hip arthritis were the initial diagnosis. A total left hip arthroplasty was performed. Ochronotic osteoarthritis was only obtained post-surgery as confirmatory diagnosis. He was again admitted mid 2022 with the same complaints on the right hip. Subsequently, he underwent a total right hip arthroplasty. Post-operative recovery and follow-ups were deemed very satisfactory.
CONCLUSIONS: Ochronosis is an unusual diagnosis for a patient who presents with typical hip arthritis. Thus, unless meticulous history taking and advanced laboratory tests, the diagnosis can easily be missed by surgeons.

OBJECTIVE: To evaluate pathological lesions suggesting the presence of rickets and to place the diagnosis into bioarchaeological and historical context.
METHODS: The remains of a 3-year ± 12-month-old child discovered during a rescue excavation in Heuvelton, New York.
METHODS: We examined the individual macroscopically and conducted a differential diagnosis following established protocols in the palaeopathological literature.
RESULTS: Bony change on the orbits, mandible, ribs, clavicles, left scapula, humerii, radii, ulnae, femora, tibiae, fibulae (e.g., porosity, diaphyseal thickening, flaring, bowing), and dental lesions were recorded.
CONCLUSIONS: We demonstrate that the child likely presented with vitamin D deficiency rickets during crawling and as they learned to walk.
CONCLUSIONS: This example offers an important contribution to the bioarchaeological literature, as few cases of rickets have been recorded in rural North America using updated diagnostic criteria and little is known of the health and lifeways of early settlers in 19th-century upstate New York.
CONCLUSIONS: It is not possible to ascertain the precise aetiology of this child\'s rachitic state and to compare this individual with others in the population.
UNASSIGNED: Examination (and re-assessment) of other North and South American skeletal assemblages for signs of vitamin D deficiency rickets following current bioarchaeological standards.

UNASSIGNED: Patients with ornithine transcarbamylase deficiency (OTCD) often present with severe hyperammonaemia. We report a case of osmotic demyelination syndrome (ODS) secondary to the treatment of hyperammonaemia due to OTCD, a disease requiring early diagnosis, as it can have a severe prognosis.
UNASSIGNED: A girl toddler was brought to the hospital with a complaint of somnolence, presenting with hyperammonaemia and liver failure, and was diagnosed with OTCD. Treatment was started immediately, and the ammonia level returned to the normal range within 24 hours. On days 13-20, another treatment was commenced for re-elevated ammonia levels, which subsequently returned to within the reference range; however, mildly impaired consciousness persisted. Hypokalaemia coincided with temporary intravenous treatment and continuous haemodialysis. T2-weighted magnetic resonance images revealed lesions as high-signal areas in the bilateral putamen on day 11 (extrapontine myelinolysis (EPM)) and in the pons on day 51 (central pontine myelinolysis (CPM)). Consequently, ODS was diagnosed.
UNASSIGNED: When interpreting magnetic resonance images of patients under acute treatment for hyperammonaemia due to OTCD, a condition that may be complicated by hypokalaemia, paying attention to findings suggesting EPM may help detect ODS before CPM appears and may improve patient prognosis.

Two case reports and an updated critical review on bilateral fractures of the femoral neck are presented. Bilateral fractures of the femoral neck have been investigated for at least 80 years and are treated as rare cases. The primary cause is usually considered an external shock; however, aside from high energy shocks (e.g., falling and impact with hard, rigid surfaces, traffic accidents, etc.) the underlying causes of femoral neck frailty have not yet been fully understood. Although not exhaustive, the review spans cases reported as early as 1944 and compares their conclusions in line with medicine developments at the time of the reports until present. The discussion is perhaps controversial at times; it brings to the fore the energy balance between shock waves and stress waves. The two cases reported here add to the review, one highlighting the biomechanics, and the other supporting more recent findings on metabolic disorders, which ultimately lead to enhanced frailty of the femoral neck. Investigation of the fractures has been performed with X-ray radiographs, MRI, and CT, with a follow up using a Doppler US to check blood flow in the lower zone of the limbs. The second case was investigated both for fractures and metabolic diseases, e.g., type I diabetes and kidney failure (dialysis). In Case 1 the second fracture was not observable at the time of admission, and therefore two surgery operations were performed at seven days interval. Taperloc Complete prostheses (Zimmer Biomet) were applied. Case 2 suffered a second fracture in the right hip in the segment above the knee and required better fixation with cables. Despite this, she returned one month later with a new crack in the femur. Case 1 is a typical case of wear consequences on the biomechanics of the hill pad-tibia-femur-femoral neck system, where tension of the neck occurred due to a stress wave rather than a shock wave. This can be proven by the absence of a second fracture from the images first acquired, the only evidence being pain and walking difficulty. Case 2 shows that metabolic diseases can dramatically enhance the frequency of bilateral femoral neck fractures.

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Methylmalonic acidemia is a rare autosomal recessive metabolic disease. However, because of the atypical clinical symptoms, the type of late-onset methylmalonic academia is often misdiagnosed. Especially when the blood vitamin B12 and folic acid levels are normal, it is not easy to think of this disease. Herein we report a 9-year-old girl who developed normally on a relatively balanced diet before 7 years of age. However, she presented with fatigue and attention deficit when she followed a vegetarian diet. Laboratory examination showed moderate macrocytic anemia, high levels of homocysteine, high level of propionylcarnitine/acetylcarnitine, urinary methylmalonic acid and methyl citrate. Gene mutation analysis showed c.609G > A and c.80A > G compound heterozygous mutations in the MMACHC gene, supported late-onset combined methylmalonic academia with homocysteinemia. Then treatment performed with add meat to the diet, vitamin B12, folic acid betaine and L-carnitine supplement. One week later, the child\'s clinical symptoms and the laboratory examinations were significantly improved.