B3GAT3-related linkeropathy and an in-frame homozygous deletion in an adult patient.

BACKGROUND: Proteoglycans (PGs) are complex macromolecules consisting of a core protein and glycosaminoglycan (GAG) side chains. PGs are important for the constitution and functioning of the connective tissue. The normal composition of the GAG side chains defines the nature of the PGs and a wide range of biological events. Deficiencies of specific enzymes involved in the linkage of GAGs to the core protein to form functional PGs, lead to a heterogeneous disease group called Linkeropathies. This is a group of multisystem conditions characterized by different phenotypes that include skeletal dysplasia and various extra-skeletal features: developmental delay/intellectual disability, ophthalmological abnormalities including blue sclerae, facial characteristics, cardiac defects, abdominal wall defects (hernias), cutis laxa, hypermobility and hypotonia. The conditions show variable severity and often overlapping phenotypes. The enzyme ß-1,3-glucuronyltransferase 3, encoded by B3GAT3, is involved in the linkage process to form functional PGs. Biallelic pathogenic variants in B3GAT3 hence lead to Linkeropathy due to loss of function or decreased activity of this enzyme. PATIENT PRESENTATION: We describe a 22-year-old female patient, born of consanguineous parents. The disease history includes congenital severe joint malalignment of elbows, hips, knees and feet, hypermobility, severe kyphoscoliosis, osteoporosis with multiple fractures in childhood, congenital diaphragmatic hernia, minor dental anomalies, digital malformations, and characteristic facial features. Whole exome sequencing was performed, and homozygosity for a novel in-frame deletion in B3GAT3, (c.61_63delCTC (p.(Leu21del))) was detected. Both unaffected parents (double second cousins) were shown to be heterozygous carriers. CONCLUSION: This is the first report to describe homozygosity for this specific in-frame deletion in B3GAT3 (p.(Leu21del)). We present a young adult phenotype and a summary of previous reported patients with other biallelic B3GAT3-variants for comparison. Previously described patients of B3GAT3-deficiency were, however, all children with phenotypes ranging from prenatal manifestation and early lethality to less severe. We suggest that this novel homozygous in-frame deletion in B3GAT3 may be the cause of a recessive form of Linkeropathy.

Awareness and Expectations Surrounding Family Planning and Pregnancy Among Danish Patients with Chronic Inflammatory Disease of the Skin or Joints: Results from an Online Survey.

BACKGROUND: Patients with chronic inflammatory diseases (CIDs) may encounter challenges in their family planning journey. Here, we report on the access to family planning and pregnancy (FPP) information and the concerns among patients in Denmark with CIDs. METHODS: Patients aged 18-50 years with CIDs participated in an online survey. Patients were recruited through patient advocacy groups and were asked to report information on their diagnosis, concerns related to FPP and perceptions of access to FPP information. Descriptive statistics were applied. RESULTS: Of the eligible respondents, 368 had rheumatological diagnoses (rheumatoid arthritis, psoriatic arthritis, juvenile idiopathic arthritis or axial spondyloarthritis; mean age 40 years; 83% women, 17% men) and 95 had dermatological diagnoses (psoriasis or psoriatic arthritis; mean age 38 years; 67% women, 33% men). Approximately 70% of all patients reported seeking FPP information from patient advocacy groups; 57% of both cohorts used the internet as information sources; and 73% and 42% of rheumatological and dermatological cohorts used their hospital and specialist doctor, respectively. Despite this, 58% and 67% of patients with rheumatological and dermatological diagnoses reported limited or no access to FPP information, with > 70% of dermatological patients of early/mid-reproductive age reporting a lack of access to this information. Overall, 68% of patients with rheumatological and 73% with dermatological diagnoses had biological children, amongst whom 24% and 18%, respectively, indicated their disease affected the number of children they ultimately decided to have. The most frequent FPP concerns among patients who did not want any/more biological children were disease worsening, heredity and taking care of the child. CONCLUSIONS: Despite awareness of available sources of FPP information, patients expressed experiencing a feeling of limited access to information and having concerns that affect key decisions regarding FPP. The results of this survey highlight a need for improved and more standardised FPP information for patients with CIDs in Denmark.

Tele-Health Followup Strategy for Tight Control of Disease Activity in Rheumatoid Arthritis: Results of a Randomized Controlled Trial.

OBJECTIVE: To test the effect of patient-reported outcome (PRO)-based tele-health followup for tight control of disease activity in patients with rheumatoid arthritis (RA), and the differences between tele-health followup performed by rheumatologists or rheumatology nurses. METHODS: A total of 294 patients were randomized (1:1:1) to either PRO-based tele-health followup carried out by a nurse (PRO-TN) or a rheumatologist (PRO-TR), or conventional outpatient followup by physicians. The primary outcome was a change in the Disease Activity Score in 28 joints (DAS28) after week 52. Secondary outcomes were physical function, quality of life, and self-efficacy. The noninferiority margin was a DAS28 score change of 0.6. Mean differences were estimated following per protocol, intent-to-treat (ITT), and multivariate imputation analysis. RESULTS: Overall, patients had low disease activity at baseline and end followup. Demographics and baseline characteristics were similar between groups. Noninferiority was established for the DAS28. In the ITT analysis, mean differences in the DAS28 score between PRO-TR versus control were -0.10 (90% confidence interval [90% CI] -0.30, 0.13) and -0.19 (90% CI -0.41, 0.02) between PRO-TN versus control. When including 1 yearly visit to the outpatient clinic, patients in PRO-TN had mean ± SD 1.72 ± 1.03 visits/year, PRO-TR had 1.75 ± 1.03 visits/year, and controls had 4.15 ± 1.0 visits/year. This included extra visits due to inflammatory flare. CONCLUSION: Among RA patients with low disease activity or remission, a PRO-based tele-health followup for tight control of disease activity in RA can achieve similar disease control as conventional outpatient followup. The degree of disease control did not differ between patients seen by rheumatologists or rheumatology nurses.