Timely diagnosis of multiple endocrine neoplasia 2B by identification of intestinal ganglioneuromatosis: a case series.

BACKGROUND: Medullary thyroid carcinoma (MTC) in childhood is rare and has an unfavorable prognosis. To improve outcome, early diagnosis is essential. In patients with multiple endocrine neoplasia type 2B (MEN2B), MTC can occur already before the age of 1 year. Recognition of non-endocrine features of MEN2B may lead to timely diagnosis. PURPOSE: To describe how early recognition of non-endocrine features can lead to a timely diagnosis of MEN2B as well as the effect of recognition of premonitory symptoms on prognosis. METHODS: A retrospective case series from the University Medical Center Utrecht/Wilhelmina Children's Hospital, a Dutch national expertise center for MEN patients. All eight MEN2B patients in follow-up between 1976 and 2020 were included and medical records reviewed. RESULTS: Intestinal ganglioneuromatosis (IGN) as the cause of gastrointestinal (GI) symptoms was detected in seven patients. In three of them within months after birth. This led to early diagnosis of MEN2B, which allowed subsequent curative thyroid surgery. On the contrary, a MEN2B diagnosis later in childhood-in three patients (also) triggered by oral neuromas/neurofibromas-led to recurrent, persistent, and/or progressive MTC in five patients. CONCLUSIONS: Neonatal GI manifestations offer the most important window of opportunity for early detection of MEN2B. By accurate evaluation of rectal biopsies in patients with early onset severe constipation, IGN can be timely detected, while ruling out Hirschsprung's disease. MEN2B gene analysis should follow detection of IGN and-when confirmed-should prompt possibly still curative thyroid surgery.

10-m Shuttle Ride Test in Youth With Osteogenesis Imperfecta Who Use Wheelchairs: Feasibility, Reproducibility, and Physiological Responses.

BACKGROUND: Physical fitness levels in youth with osteogenesis imperfecta (OI) who use wheelchairs are unknown. The 10-m Shuttle Ride Test (SRiT) has recently been introduced as a field test to determine cardiorespiratory fitness in children with cerebral palsy who self-propel a wheelchair. OBJECTIVE: The purpose of this study was to investigate the feasibility and reproducibility of the SRiT, as well as the physiological responses to the SRiT, in youth with moderate-to-severe OI between 8 and 25 years of age who self-propel a wheelchair at least for long distances. DESIGN: A test-retest design was used. METHODS: Thirteen patients with OI (8 boys, 5 girls; mean±SD values for age=15.5±6.4 years) using a manual wheelchair performed 2 SRiTs within 2 weeks. Adverse events, reached stage, peak heart rate (HRpeak), peak respiratory exchange ratio (RERpeak), peak oxygen uptake (V̇o2peak), and peak minute ventilation (V̇epeak) were the main outcome parameters. RESULTS AND DISCUSSION: All participants performed a maximal effort at both SRiTs (mean±SD values for HRpeak of 195±9 beats per minute [bpm], RERpeak of 1.32±0.16, V̇o2peak of 25.4±5.6 mL·kg(-1)·min(-1), and V̇epeak of 47.9±18.6 L·min(-1)), without adverse events. The intraclass correlation coefficient of the reached stage showed excellent reliability (.95). Limits of agreement (LoA) analysis revealed acceptable LoA for reached stage (mean bias=-0.58, range=-2.50 to +1.35). There was a low correlation between reached stage and V̇o2peak (r=.61 and r=.45 for the first and second SRiTs, respectively). LIMITATIONS: The influence of wheelchair properties and individually adjusted wheelchair designs was not examined. CONCLUSIONS: The SRiT appears to be a feasible, safe, and reproducible maximal field test in youth with OI using wheelchairs at least for long distances. This field test might be useful to provide an indication of physical fitness and to assess the efficacy of interventions on physical fitness in these patients.

Efficacy and Safety of Bisphosphonate Therapy in Children with Osteogenesis Imperfecta: A Systematic Review.

BACKGROUND/AIMS: To systematically assess contemporary knowledge regarding the effectiveness and safety of bisphosphonates (BPs) in children with osteogenesis imperfecta (OI). METHODS: PubMed/MEDLINE, Embase, and Cochrane were searched for eligible articles up to June 2014. Studies eligible for inclusion were (randomized) controlled trials assessing the effects of BPs in children with OI. Methodological quality was assessed independently by 4 reviewers using the Cochrane Collaboration's tool for risk of bias. RESULTS: Ten studies (519 children) were included. Four studies (40%) showed a low risk of bias. All studies investigating lumbar spine areal bone mineral density indicated a significant increase as a result of BP treatment. Most studies observed a significant decrease in fracture incidence. The most frequently reported adverse events were gastrointestinal complaints, fever, and muscle soreness. A significant decrease in (bone) pain due to BP treatment was observed in more than half of the studies. Most studies measuring urinary markers of bone resorption reported a significant decrease. The majority of studies with intravenous treatment showed a significant increase in lumbar projection area, whereas studies with oral treatment did not. CONCLUSIONS: Treatment with oral or intravenous BPs in children with OI results in an increase in bone mineral density and seems to be safe and well tolerated.