BACKGROUND: Leukoencephalopathy with vanishing white matter (VWM) is an autosomal recessive disorder affecting the white matter of the brain. It typically manifests during childhood, with clinical features including sudden and severe neurological deterioration triggered by stressors such as febrile illness, minor head trauma, or stressful events. Adult-onset cases of VWM are exceptionally uncommon.
METHODS: In this case, we present an adult patient who exhibited late-onset progressive VWM characterized by ataxia, postural instability, cognitive impairment, and emotional disturbances. Comprehensive screening for endocrine, metabolic, tumor, and immunologic disorders yielded normal or negative results. Brain imaging revealed diffuse and confluent hyperintensity in the white matter on T2-weighted images, along with periventricular cavitations. Genetic testing confirmed the diagnosis of VWM, identifying two heterozygous variants in the eukaryotic translation initiation factor 2B subunit γ (EIF2B3) gene: a pathogenic variant, c.1037 T > C (p.I346T), and a variant of undetermined significance, c.22A > T (p.M8L). Upon a 2-year follow-up, the patient\'s symptoms deteriorated rapidly following a COVID-19 infection.
CONCLUSIONS: In conclusion, we have presented a case of classical adult-onset VWM. Since there are no cures or definitive treatments for the disease, it\'s extremely important to focus on early diagnosis and the prevention of stressors to avoid acute deterioration.

Bartter syndrome (BS) is a rare, inherited salt-losing renal tubular disorder characterized by secondary hyperaldosteronism, hypokalemia, hypochloremia, metabolic alkalosis, and low-to-normal blood pressure. Classic BS, or BS Type 3, the most common subtype in the Asian population, is caused by a molecular defect in ClC-Kb, a voltage-gated chloride channel in renal tubules, due to CLCNKB gene mutation. Because the onset of BS is more common in children than in adults, the diagnosis, treatment outcomes, genotype/phenotype association, and follow-up of adult-onset BS Type 3 are limited. This case report describes the findings in a 20-year-old man who was admitted with hypokalemic paralysis, with clinical manifestations were similar to those of Gitelman syndrome (GS); however, the patient was later diagnosed to have BS Type 3 through genetic testing (NM_000085.4 (CLCNKB): c.1052G>T). A literature review showed that no homozygous mutations have been reported to date. After 5 years of treatment and follow-up, we found that this genotype requires high levels of potassium and is prone to urinary protein and metabolic syndrome. Distinguishing adult-onset BS from GS is challenging in clinical practice. However, genetic diagnosis can help solve this problem effectively, and genotypes play a guiding role in treatment planning.

MECR-related neurologic disorder, also known as mitochondrial enoyl CoA reductase protein-associated neurodegeneration (MEPAN) or dystonia with optic atrophy and basal ganglia abnormalities in childhood (MIM: #617282), is an autosomal recessive inherited disease characterized by a progressive childhood-onset movement disorder and optic atrophy. Here we report a 19-year-old male, presented with progressive visual failure, nystagmus, and right orbital pain, with no history of movement or eye disorder in his childhood. His visual decline started at age 18 years, whereas nystagmus emerged seven months later. Analysis of whole-exome sequencing (WES) revealed a homozygous recurrent variant (NM_016011.5:c.772C > T, p.Arg258Trp) in MECR. These findings suggest phenotypic heterogeneity in MECR-related neurologic disorder, thus, more relevant case screening, will help to delineate the genotype-phenotype correlation of the MECR gene.

UNASSIGNED: To help in diagnosis and treatment of adult-onset Mendelian Susceptibility to Mycobacterial Disease (MSMD).
UNASSIGNED: We reported a 27-year-old man who had disease onset at 18 years. Then we reviewed previous reports of adult-onset MSMD patients, and summarized their clinical characteristics.
UNASSIGNED: The case was diagnosed as MSMD with tyrosine kinase 2 (TYK2) mutation and had dramatic improvement after treatment. In addition to our presented case and through a review of the literature, 12 cases in total were included in our study. Average age of disease onset was 29.4 years. Medium delay of diagnosis was 2.5 years. Four were with IFN-γR1 deficiency, four with IL-12β1 deficiency, two with NEMO deficiency, one with TYK2 deficiency and one with STAT1 deficiency. Common symptoms were lymphadenopathy (6/12, 50.0 %), weight loss (6/12, 50.0 %), bone/joint pain (5/12, 41.7 %), fever (4/12, 33.3 %) and gastrointestinal symptoms (4/12, 33.3 %). Mycobacteria caused infections in lymph nodes (7/12, 58.3 %), bone/joint (5/12, 41.7 %) and skin (5/12, 41.7 %). After treatment, eight (66.7 %) got favorable prognosis, two (16.7 %) died and one (16.7 %) was unknown.
UNASSIGNED: Adult-onset MSMD have complex clinical presentations and are difficult to recognize, which results in delayed diagnosis. However, once identified, antibiotics and IFN-γ might have good efficacy. Therefore, when encountering adult patients with recurrent and refractory mycobacterial infections, especially in lymph nodes, bone/joints, and skin, MSMD should be considered.

OBJECTIVE: To assess the correlation between serum uric acid (UA) level and diabetic kidney disease among adult-onset Type 1 diabetes mellitus (T1DM) patients in China.
METHODS: A total of 184 patients with adult-onset T1DM between January 2014 and December 2016 were recruited, with demographics and medical data collected. Comparisons were performed between according to different serum UA gender-specific quartiles. Relationship between serum UA level with urinary ACR and eGFR was also assessed.
RESULTS: Median urinary ACR and eGFR were 21.55 [10.79, 45.02] mg/g and 113.86 [88.43, 143.61] ml/min/1.73 m2, respectively. The median UA was 257.4 (208.2-334.8) μmol/L. Participants with higher serum UA levels had higher urinary ACR and lower eGFR than those with lower UA (P < 0.05). Higher serum UA level was significantly associated with higher urinary ACR in Spearman\'s correlational analysis (P = 0.006) and multiple stepwise regression analysis (P = 0.013). The association between serum UA and urinary ACR was not linear, but showed a curve correlation, which also showed in the sensitivity analysis. Serum UA in the upper gender-specific quartile, was associated with lower eGFR (P < 0.001) and showed an independent negative correlation with eGFR in multiple stepwise regression analysis (P < 0.001).
CONCLUSIONS: The serum UA level was negatively correlated with eGFR and had a curve correlation with urinary ACR in adult-onset T1DM patients of China.

Focal and segmental glomerulosclerosis (FSGS) is a histological pathology that characterizes a wide spectrum of diseases. Many genes associated with FSGS have been studied previously, but there are still some FSGS families reported in the literature without the identification of known gene mutations. The aim of this study was to investigate the new genetic cause of adult-onset FSGS.
This study included 40 FSGS families, 77 sporadic FSGS cases, 157 non-FSGS chronic kidney disease (CKD) families and 195 healthy controls for analyses. Whole-exome sequencing (WES) and Sanger sequencing were performed on probands and family members of all recruited families and sporadic FSGS cases.
Using WES, we have identified a novel heterozygous missense variant (c.T1655C:p.V552A) in exportin 5 gene (XPO5) in two families (FS-133 and CKD-05) affected with FSGS and CKD. Sanger sequencing has confirmed the co-segregation of this identified variant in an autosomal dominant pattern within two families, while this variant was absent in healthy controls. Furthermore, the identified mutation was absent in 195 ethnically matched healthy controls by Sanger sequencing. Subsequently, in silico analysis demonstrated that the identified variant was highly conservative in evolution and likely to be pathogenic.
Our study reports an adult-onset autosomal dominant inheritance of the XPO5 variant in familial FSGS for the first time. Our study expanded the understanding of the genotypic, phenotypic and ethnical spectrum of mutation in this gene.

The aim of this research is to discuss the research status, hotspots, frontiers and development trends in the field of adult-onset Still\'s disease (AOSD) based on bibliometrics and visual analysis by CiteSpace software.
The relevant research articles on AOSD from 1921 to 2021 were retrieved from the Scopus database. CiteSpace software was used to form a visual knowledge map and conduct analysis for the countries/regions, journals, authors, keywords, clusters, research hotspots and frontiers of the included articles.
There were 2,373 articles included, and the number of articles published during 1921-2021 is increasing. The country with the highest number of articles published was Japan (355, 14.96%), followed by the United States (329, 13.86%) and France (215, 9.06%). The author with the highest number of publications is Ansell, Barbara M. (30, 1.26%), and the author with the highest co-citation frequency is Yamaguchi, Masaya (703). Clinical Rheumatology is the journal with the highest publication frequency. The top five cluster groups were \"joint\", \"differential diagnosis\", \"prednisolone\", \"methotrexate\" and \"macrophage activation syndrome\". The diagnosis, treatment and pathogenesis of AOSD form the main research fields, and prognosis and complications are the research hotspots and trends.
The global research field in AOSD has expanded in the past 100 years. The complications and new pathogenesis of AOSD are hotspots in this field and need further study in the future.

Leukoencephalopathy with vanishing white matter (LVWM) is an autosomal recessive disease. Ovarioleukodystrophy is defined as LVWM in females showing signs or symptoms of gradual ovarian failure. We present a 38-year-old female with ovarioleukodystrophy who showed status epilepticus, gait instability, slurred speech, abdominal tendon hyperreflexia, and ovarian failure. Abnormal EEG, characteristic magnetic resonance, and unreported EIF2B5 compound heterozygous mutations [c.1016G>A (p.R339Q) and c.1157G>A (p.G386D)] were found. Furthermore, the present report summarizes 20 female patients with adult-onset ovarioleukodystrophy and EIF2B5 gene mutations. In conclusion, a new genetic locus for LVWM was discovered. Compared with previous cases, mutations at different EIF2B5 sites might have different clinical manifestations and obvious clinical heterogeneity.

To analyze the clinical, imaging, and genetic characteristics of a patient diagnosed with adult-onset Krabbe disease (KD). Clinical and imaging features of the patient were retrospectively reviewed. The patient, a 40-year-old female, presented adult-onset spastic paraplegia. Brain magnetic resonance imaging (MRI) showed white matter hyperintensities along bilateral optic radiations. Colorimetry of galactocerebrosidase enzyme activity showed low enzyme levels. A heterozygous missense mutation: c.1658G>A (p.G553E) and c.1901T>C (p.L634S) was identified in the GALC gene by whole exome sequencing, and was verified by Sanger sequencing. KD should be considered when patients presented adult-onset spastic paraplegia with classical MRI imaging features. Mutation c.1658G>A (p.G553E) was novel in GALC gene and broaden the mutation spectrum.

BACKGROUND: Previous reports have described hypogonadism associated with virus infection such as hantavirus, human immunodeficiency virus (HIV) or severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). However, to our best knowledge there has been no case report of secondary hypogonadism following hand, foot, and mouth disease (HFMD).
METHODS: A previously healthy 28-year-old man with no history of major physical and psychological trauma, presented with bilateral gynecomastia and erectile dysfunction 2 weeks after HFMD. Laboratory testament showed the level of gonadotropin hormones declined. Imaging examination demonstrated no major abnormal change in pituitary or reproductive system. The diagnosis of hypogonadism was established. Then the patient was ordered to maintain mental health outward of hospital without drug intervention. One month after presentation, his gonadotropin hormone level and sexual desire had recovered, while bilateral gynecomastia and erectile dysfunction symptoms disappeared.
CONCLUSIONS: Physicians should notice the possibility for hypogonadism in adult patients with a recent history of HFMD.