Juvenile onset Parkinsonism with “pure nigral” degeneration and POLG1 mutation

Abstract Background The preservation or restoration of β cell function in type 1 diabetes (T1D) remains as an attractive and challengeable therapeutic target. Mesenchymal stromal cells (MSCs) are multipotent cells with high capacity of immunoregulation, which emerged as a promising cell-based therapy for many immune disorders. The objective of this study was to examine the efficacy and safety of one repeated transplantation of allogeneic MSCs in individuals with T1D. Methods This was a nonrandomized, open-label, parallel-armed prospective study. MSCs were isolated from umbilical cord (UC) of healthy donors. Fifty-three participants including 33 adult-onset (≥ 18 years) and 20 juvenile-onset T1D were enrolled. Twenty-seven subjects (MSC-treated group) received an initial systemic infusion of allogeneic UC-MSCs, followed by a repeat course at 3 months, whereas the control group (n = 26) only received standard care based on intensive insulin therapy. Data at 1-year follow-up was reported in this study. The primary endpoint was clinical remission defined as a 10% increase from baseline in the level of fasting and/or postprandial C-peptide. The secondary endpoints included side effects, serum levels of HbA1c, changes in fasting and postprandial C-peptide, and daily insulin doses. Results After 1-year follow-up, 40.7% subjects in MSC-treated group achieved the primary endpoint, significantly higher than that in the control arm. Three subjects in MSC-treated group, in contrast to none in control group, achieved insulin independence and maintained insulin free for 3 to 12 months. Among the adult-onset T1D, the percent change of postprandial C-peptide was significantly increased in MSC-treated group than in the control group. However, changes in fasting or postprandial C-peptide were not significantly different between groups among the juvenile-onset T1D. Multivariable logistic regression assay indicated that lower fasting C-peptide and higher dose of UC-MSC correlated with achievement of clinical remission after transplantation. No severe side effects were observed. Conclusion One repeated intravenous dose of allogeneic UC-MSCs is safe in people with recent-onset T1D and may result in better islet β cell preservation during the first year after diagnosis compared to standard treatment alone. Trial registration ChiCTR2100045434. Registered on April 15, 2021—retrospectively registered, http://www.chictr.org.cn/

Download Full-text

Cerebrotendinous Xanthomatosis: diversity of presentation and refining treatment with chenodeoxycholic acid

Cerebellum & Ataxias ◽

10.1186/s40673-021-00128-2 ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Mahjabin Islam ◽

Nigel Hoggard ◽

Marios Hadjivassiliou

Keyword(s):

Chenodeoxycholic Acid ◽

Clinical Characteristics ◽

Spastic Paraparesis ◽

Acid Synthesis ◽

Bile Acid Synthesis ◽

Cerebrotendinous Xanthomatosis ◽

Juvenile Onset ◽

Progressive Ataxia ◽

Classical Triad ◽

High Index Of Suspicion

Abstract Background Cerebrotendinous xanthomatosis (CTX) is a rare but treatable neurometabolic disorder of lipid storage and bile acid synthesis. Whilst CTX is said to present with the classic triad of juvenile onset cataracts, tendon xanthomata and progressive ataxia, the diversity of presentation can be such that the diagnosis may be substantially delayed resulting in permanent neurological disability. Methods A retrospective review of the clinical characteristics and imaging findings of 4 patients with CTX presenting to the Sheffield Ataxia Centre over a period of 25 years. Results Although CTX-related symptoms were present from childhood, the median age at diagnosis was 39 years. Only 1 of the 4 cases had tendon xanthomata, only 2 cases had juvenile onset cataracts and 3 had progressive ataxia with one patient presenting with spastic paraparesis. Serum cholestanol was elevated in all 4 patients, proving to be a reliable diagnostic tool. In addition, cholestanol was raised in the CSF of 2 patients who underwent lumbar puncture. Despite treatment with chenodeoxycholic acid (CDCA) and normalization of serum cholestanol, CSF cholestanol remained high in one patient, necessitating increase in the dose of CDCA. Further adjustments to the dose of CDCA in the patient with raised CSF cholestanol resulted in slowing of progression. Two of the patients who have had the disease for the longest continued to progress, one subsequently dying from pneumonia. Conclusion A high index of suspicion for CTX, even in the absence of the classical triad is essential in reaching such diagnosis. The earlier the diagnosis and treatment, the better the outcome.

Download Full-text

Association of microRNA-125a with the clinical features, disease activity and inflammatory cytokines of juvenile-onset lupus patients

Lupus ◽

10.1177/09612033211010328 ◽

2021 ◽

pp. 096120332110103

Author(s):

Eman Eissa ◽

Botros Morcos ◽

Rania Fawzy Mahmoud Abdelkawy ◽

Hanan H Ahmed ◽

Naglaa M Kholoussi

Keyword(s):

Disease Activity ◽

Inflammatory Cytokines ◽

Lupus Erythematosus ◽

Plasma Levels ◽

Clinical Manifestations ◽

Juvenile Onset ◽

Expression Levels ◽

Ifn Γ ◽

Chronic Autoimmune Disease ◽

Normal Controls

Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with marked variation in its clinical presentation. Juvenile-onset SLE (jSLE) exhibits an aggressive clinical phenotype and severe complications. Dysregulated expression of microRNAs (miRs) in immune cells from patients with SLE has been found. We aim to evaluate the association of miR-125a with the clinical and laboratory characteristics, disease activity and inflammatory cytokines of jSLE patients. Methods 60 jSLE patients and 25 normal controls were involved in the study. The expression pattern of miR-125a was determined in plasma of all subjects using qRT-PCR. In addition, plasma levels of IL-17 and IFN-γ were examined using ELISA. The correlation of miR-125a expression with the clinical manifestations and disease activity of jSLE patients was analyzed. Also, its association with the inflammatory cytokines was investigated in jSLE patients. Results Our findings showed that miR-125a expression levels were significantly reduced in jSLE patients compared to normal controls ( p < 0.01) and these expression levels differed based on the clinical variability of patients. In addition, plasma levels of IL-17 and IFN-γ in jSLE patients were significantly higher than healthy controls ( p < 0.01). Finally, miR-125a expression had significant negative associations with each of SLEDAI-2K ( p < 0.01), SLICC ( p < 0.01), ESR ( p < 0.05), proteinuria ( p < 0.01) and IL-17 levels ( p < 0.01) in jSLE patients. Conclusion Our findings postulate that miR-125a could act as a candidate therapeutic target for its possible regulation of inflammation in jSLE patients.

Download Full-text

Exercise limitation in juvenile onset Mixed Connective Tissue Disease (MCTD)

Pediatric Rheumatology ◽

10.1186/1546-0096-6-s1-p162 ◽

2008 ◽

Vol 6 (Suppl 1) ◽

pp. P162 ◽

Cited By ~ 1

Author(s):

JJ Net ◽

A van Royen-Kerkhof ◽

T Takken ◽

B Wissink

Keyword(s):

Connective Tissue ◽

Connective Tissue Disease ◽

Mixed Connective Tissue Disease ◽

Juvenile Onset ◽

Exercise Limitation

Download Full-text

HPV Strain Predicts Severity of Juvenile-Onset Recurrent Respiratory Papillomatosis with Implications for Disease Screening

Cancers ◽

10.3390/cancers13112556 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2556

Author(s):

Mary C. Bedard ◽

Alessandro de Alarcon ◽

Yann-Fuu Kou ◽

David Lee ◽

Alexandra Sestito ◽

...

Keyword(s):

Gene Expression ◽

Disease Severity ◽

Disease Onset ◽

Tissue Bank ◽

Benign Neoplasm ◽

Recurrent Respiratory Papillomatosis ◽

Clinical Severity ◽

Viral Gene ◽

Juvenile Onset ◽

Severity Scores

Juvenile-onset recurrent respiratory papillomatosis (JoRRP) is the most common benign neoplasm of the larynx in children, presenting with significant variation in clinical course and potential for progression to malignancy. Since JoRRP is driven by human papillomavirus (HPV), we evaluated viral factors in a prospective cohort to identify predictive factors of disease severity. Twenty children with JoRRP undergoing routine debridement of papillomas were recruited and followed for ≥1 year. Demographical features, clinical severity scores, and surgeries over time were tabulated. Biopsies were used to establish a tissue bank and primary cell cultures for HPV6 vs. HPV11 genotyping and evaluation of viral gene expression. We found that patients with HPV11+ disease had an earlier age at disease onset, higher frequency of surgeries, increased number of lifetime surgeries, and were more likely to progress to malignancy. However, the amplitude of viral E6/E7 gene expression did not account for increased disease severity in HPV11+ patients. Determination of HPV strain is not routinely performed in the standard of care for JoRRP patients; we demonstrate the utility and feasibility of HPV genotyping using RNA-ISH for screening of HPV11+ disease as a biomarker for disease severity and progression in JoRRP patients.

Download Full-text