Case report: marfan syndrome (MFS) mimicking cutaneous vasculitis.

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder caused by variants in the extracellular microfibril fibrillin (FBN1) gene. Here we report an FBN1 variant in a child with an unusual skin rash mimicking cutaneous vasculitis, and mild aortic root dilatation. The case was complicated by lack of typical skeletal MFS phenotype; and severe needle phobia preventing any blood testing for workup of suspected vasculitis. Therefore inflammatory markers, autoantibody profile and general hematology/biochemistry results were unknown. Diagnosis of MFS was made via genetic testing of a saliva sample alone using a next-generation sequencing (NGS) targeted gene panel designed to screen for monogenic forms of vasculitis and noninflammatory vasculopathic mimics. This revealed the patient was heterozygous for a pathogenic frameshift variant in FBN1; NM_000138, c.1211delC, p.(Pro404Hisfs*44), predicted to cause premature protein truncation leading to loss of function. The variant has not been detected in control populations and has previously been detected in individuals with MFS. This rapid diagnosis significantly impacted the patient management: avoidance of invasive investigations; avoidance of unnecessary immunosuppression; facilitating genetic counselling of the index case and family; and directly informing lifelong monitoring and ongoing treatment for aortic root involvement from MFS. This case further emphasizes the diagnostic utility of NGS early in the diagnostic workup of paediatric patients referred with suspected vasculitis, and we emphasize that MFS can present with cutaneous vasculitic-like features in the absence of the typical Marfanoid skeletal phenotype.

Acromesomelic Dysplasia, Type Maroteaux: Impact of Long-Term (8 Years) High-Dose Growth Hormone Treatment on Growth Velocity and Final Height in 2 Siblings.

INTRODUCTION: Acromesomelic dysplasia, type Maroteaux (AMDM) is a rare autosomal recessive skeletal dysplasia, characterized by severe dwarfism and disproportionate limb shortening. It results from loss-of-function NPR2 mutations affecting the C-type natriuretic peptide receptor. Resistance to growth hormone (GH) action has previously been suggested. We describe outcomes of 2 siblings with AMDM after prolonged high-dose GH treatment. PATIENTS/METHODS: Two siblings (Pt-A and Pt-B; consanguineous parents) presented in early childhood with severe disproportionate short stature and radiological features of AMDM. Subsequent genetic testing identified a novel homozygous NPR2 mutation. GH provocation testing showed relatively high GH levels. Serum insulin-like growth factor 1 (IGF-1) was ∼2 SD below age/sex-specific mean. High-dose GH (0.075 mg/kg/day) was started. Pre-GH height velocities were 3.7 (Pt-A) and 4.5 (Pt-B) cm/year. GH dose was adjusted to sustain serum IGF-1 towards +3 SDS for age/sex. Annualized height velocities for first 3 years on GH were 7.0, 5.4, and 4.7 cm/year for patient A and 9.4, 8.0, and 5.9 cm/year for patient B. Height gain during puberty was 10.6 (Pt-A) and 5.9 (Pt-B) cm. Final heights after 8.5 years of GH treatment were 130.5 cm (-6.57 SDS, Pt-A) and 134 cm (-4.58 SDS, Pt-B). CONCLUSIONS: To the best of our knowledge, this is the first report of final height in patients with AMDM after long-term GH treatment. Our results confirm the finding of relative GH resistance in AMDM, which when overcome with high-dose GH treatment resulted in improved height SDS during childhood and adolescence and associated quality of life. The final height of our patients was significantly higher than average reported final height (120 cm) of AMDM patients.

Cognitive changes after surgery vs stenting for carotid artery stenosis.

OBJECTIVES: Cognitive function has not been evaluated systematically in the context of carotid endarterectomy (CEA) versus carotid artery stenting (CAS). Cognitive decline can occur from microembolization or hypoperfusion during CEA or CAS. Carotid revascularization may, however, also improve cognitive dysfunction resulting from chronic hypoperfusion. We compared cognitive outcomes in consecutive asymptomatic patients undergoing CAS or CEA. METHODS: This is a prospective nonrandomized single-center study of patients with asymptomatic carotid stenosis ≥ 70% undergoing CAS or CEA using standard techniques. Neurologic symptoms were evaluated by history, physical examination, and the National Institutes of Health Stroke Scale. A 50-minute cognitive battery was performed 1 to 3 days before and 4 to 6 months after CEA/CAS. The tests (Trail Making Tests A/B, Processing Speed Index (PSI) of the Wechsler Adult Intelligence Scale - Third Edition (WAIS-III), Boston Naming Test, Working Memory Index (WMI) of the Wechsler Memory Scale - Third Edition (WMS-III), Controlled Oral Word Association, and Hopkins Verbal Learning Test) for six cognitive domains (motor speed/coordination and executive function, psychomotor speed, language (naming), working memory/concentration, verbal fluency, and learning/memory) were conducted by a neuropsychologist. The primary analysis of impact of treatment modality was a normalized cognitive change score. RESULTS: Forty-six patients underwent prepost testing (CEA = 25, CAS = 21). Women comprised 36% of the cohort, mean preprocedural stenosis was 84%, and 54% were right-sided lesions. All patients were successfully revascularized without periprocedural complications. The scores for each test improved after CEA except WMI, which decreased in 20 of 25 patients. Improvement occurred in all tests after CAS except PSI, which decreased in 18 of 21 patients. In addition to comparing the changes in individual test scores, overall cognitive change was measured by calculating the change in composite cognitive score (CCS) postprocedure versus baseline. To compute the CCS, the raw scores from each test were transformed into z scores and then averaged to calculate each patient's composite score. The composite score at baseline was then compared with that from the postprocedure testing. The CCS improved after both CEA and CAS, and the changes were not significantly different between the groups (.51 vs .47; P = NS). CONCLUSIONS: Carotid revascularization results in an overall improvement in cognitive function. There are no differences in the composite scores of five major cognitive domains between CEA and CAS. When individual tests are compared, CEA results in a reduction in memory, while CAS patients show reduced psychomotor speed. Larger studies will help confirm these findings.

Clinical consequences of MRI activity in treated multiple sclerosis.

BACKGROUND: Inflammation on brain MRI is the most sensitive marker of disease activity in multiple sclerosis (MS) but its clinical consequences remain controversial. OBJECTIVE: Here we investigated the clinical consequences of MRI activity in MS subjects treated with two different first line disease modifying agents. METHODS: Seventy-five treatment-naïve subjects with relapsing-remitting MS (N = 61) or clinically isolated syndromes at risk of MS (N = 14) from the BECOME study that had been randomized to interferon beta-1b (N = 39) or glatiramer acetate (N = 36) and followed for up to two years by monthly brain MRI optimized to detect inflammatory activity were studied for the clinical consequences of lack of MRI remission. RESULTS: MRI remission occurred in 46.4% of participants transiently and in 23.2% completely while it was never achieved in 30.4%. There was no difference by treatment in MRI remission, progression of physical disability, or cognitive function. The percentage of relapse-free subjects was 87.5% for the group in complete MRI remission, 47.6% in the group never in remission and 59.4% in the group in transient remission (p = 0.017). Similar differences were observed for six-month-confirmed worsening of ambulatory function as measured by the timed 25 foot walk (p = 0.026) and by Expanded Disability Status Scale (EDSS) (p = 0.10). Cognitive function was lowest at baseline for the group that never reached MRI remission on treatment; this group improved the least upon repeated cognitive testing during the two years of treatment (p < 0.001). CONCLUSIONS: Lack of MRI remission during treatment with interferon beta-1b or glatiramer acetate is associated with higher relapse rate and worsening of physical and cognitive function.

Purification and analysis of DNases of Tritrichomonas foetus: evidence that these enzymes are glycoproteins.

Tritrichomonas foetus is the causative agent of trichomoniasis. In cattle, infection results in economic losses to the beef and dairy industries due to abortion and infertility. Soluble DNases of T. foetus that play a role in pathogenesis and are potential therapeutic targets, were extracted and purified utilising lectin affinity chromatography. The DNases were bound to and eluted from Concanavalin A (Con A)-sepharose indicating that they are glycoproteins with alpha-linked mannose or glucose residues. The nature of the glycans carried on the eluted proteins in the fraction containing DNase activity was assessed using an enzyme-linked lectin assay. The lectin binding studies predict the presence of both N- and O-type glycans. Manganese was a potent (33%) activator of the DNase(s) whereas zinc inhibited enzyme activity by approximately 66%. The DNase(s) had a pH optimum of 4 and a molecular weight of 160 kDa. The DNase(s) were able to completely degrade DNA from animal, plant, fungal, yeast and bacterial sources, but did not significantly degrade RNA.

Addressing the impact of foster care on biological children and their families.

This study explores from a dual perspective the impact of the fostering process on biological children in the home. Ten foster parents and their biological children were interviewed separately. The impact of foster care on the psychological, educational, and social well-being of biological children and their relationship with parents and siblings were examined. The exploration reveals a paradoxical and life-changing process as seen through the eyes of biological children and their parents.