Normalization Time of Celiac Serology in Children on a Gluten-free Diet.

OBJECTIVES: Response to a gluten-free diet (GFD) in children with celiac disease is determined by symptom resolution and normalization of serology. We evaluated the rate of normalization of the transglutaminase (TTG) and antiendomysial (EMA) for children on a GFD after diagnosis. METHODS: Celiac serologies were obtained over 3.5 years after starting a GFD in 228 newly diagnosed children with biopsy-proven celiac disease. Patients were classified into categories based on serology (group A, TTG ≥10 × upper limit of normal [ULN] and EMA ≥ 1:80; group B, TTG ≥10 × ULN and EMA ≤ 1:40; and group C, TTG <10 × ULN) and by severity of histologic injury at diagnosis. RESULTS: In children with the highest serology at diagnosis (group A), 79.7% had an abnormal TTG at 12 months after diagnosis (mean TTG 12 months, 68.8 ±â€Š7.3, normal <20 kU/L). At 2 years, an abnormal TTG persisted in 41.7%. In contrast, only 35% of children with the lowest serology at diagnosis (group C) displayed an abnormal TTG at 12 months (mean TTG 14.3 ±â€Š1.9 kU/L). In those with the most severe mucosal injury, Marsh 3C, 74.2% and 33.2% had an abnormal TTG at 1 and 2 years. CONCLUSIONS: Normalization of celiac serology took >1 year in approximately 75% of GFD-compliant children with the highest celiac serology or most severe mucosal injury at diagnosis. Clinicians must consider serology and histology at diagnosis to properly evaluate response to GFD.

Evaluation of the ESPGHAN Celiac Guidelines in a North American Pediatric Population.

OBJECTIVES: We retrospectively examined the performance of the tissue transglutaminase (TTG), endomysial antibody (EMA) tests, and the ESPGHAN (European Society of Paediatric Gastroenterology, Hepatology and Nutrition) nonbiopsy criteria in a pediatric population. METHODS: Consecutive celiac serologies and corresponding intestinal biopsy results were obtained on children <18 years old over 3.5 years. Patients were classified into three categories: positive TTG, negative TTG, and IgA deficiency. RESULTS: Of the 17,505 patients with celiac serology performed, 775 had a positive TTG, 574 with a negative TTG were biopsied, and 25 were IgA deficient. Of the patients with a TTG ≥10 × upper limit of normal (ULN), positive EMA, and symptoms, 98.2% had biopsies consistent with celiac disease (CD). Four human leukocyte antigen (HLA) DQ2/DQ8-positive patients who met the ESPGHAN nonbiopsy criteria did not have CD. In the group with a TTG 3-10 × ULN, 75.7% EMA-positive patients and only 40% EMA-negative patients had CD (P<0.001). Of those with a TTG 1-3 × ULN, 52.2% EMA-positive patients vs. only 13.3% EMA-negative patients had CD (P<0.01). Of the patients with bulbar and duodenal biopsies, 9.8% had CD confined only in the bulb, especially those with a low titer TTG (P<0.01). CD prevalence in our cohort was 34.6%. Sensitivity, specificity, and positive predictive value of the TTG were 98.7%, 86.4%, and 79.4%, respectively. CONCLUSIONS: The TTG is a very sensitive screen for CD, but positive predictive value improves with a positive EMA titer. To apply the new ESPGHAN guidelines, clinicians must understand the performance of their celiac serology tests.

Motor neuron degeneration in a 20-week male fetus: spinal muscular atrophy type 0.

BACKGROUND: Neuropathological changes in degenerating motor neurons are well documented in the term neonate with spinal muscular atrophy, but not at midgestation. METHODS: Postmortem neuropathological examination was performed in a 20-week male fetus with a hypoplastic left cardiac anomaly. RESULTS: Selective degeneration of spinal and hypoglossal motor neurons was an incidental finding. Degenerating motor neurons were not immunoreactive with neuronal nuclear antigen (NeuN) or neuron-specific enolase (NSE), as were the normal motor neurons. Synaptophysin reactivity was reduced around the soma of degenerating normal motor neurons. Ubiquitin and tau were expressed in degenerating motor neurons. Gliosis, inflammation and microglial activation were lacking in the ventral horns of the spinal cord. Laryngeal striated muscle was unaltered for age. No cerebral malformations or hypoxic-ischaemic changes were found. CONCLUSION: This case represents an early motor neuronal degeneration and corresponds to the recently described "type 0" spinal muscular atrophy. Lack of contractures is attributed to the early fetal age, since most muscular growth occurs in the second half of gestation.

Subscapular tumoral calcinosis in a toddler: case report.

Tumoral calcinosis is uncommon in toddlers, and rare within the subscapular area. Although typically benign, tumoral calcinosis is often incorrectly diagnosed prior to biopsy. We present a case of subscapular tumoral calcinosis in a 16-month old girl and discuss the radiological findings on X-ray, ultrasound, computed tomography and magnetic resonance imaging, including the first description of T1-weighted post contrast imaging, which demonstrate the fibrotic components of tumoral calcinosis.

Fetal opercular cavernous angioma causing cerebral cleft: contralateral primitive vascular anomaly and subicular dysgenesis.

We describe a 22-week female fetus after pregnancy was terminated because of fetal magnetic resonance imaging showing a large left cerebral hemispheric cleft suggestive of porencephaly or schizencephaly. Postmortem examination revealed a large cavernous angioma of the left opercular region with evidence of previous hemorrhage and extensive cerebral infarction. In the right hemisphere, another vascular malformation within the frontal germinal matrix consisted of an aggregate of primitive vessels not yet canalized. Selective dysgenesis of the right subiculum also was demonstrated. This case illustrates not only a severe encephaloclastic effect of cavernous angioma in fetal brain but also the importance of fetal autopsy to help correlate and explain fetal neuroimaging. Potential future prenatal treatment of fetal angiomata requires precise in utero diagnosis.

Synaptophysin immunoreactivity in the human hippocampus and neocortex from 6 to 41 weeks of gestation.

To assess the synaptic vesicle protein synaptophysin as a potential marker for maturation in the human fetal brain, synaptophysin immunoreactivity (sIR) was prospectively studied in postmortem sections of 162 normal human fetal and neonatal brains of both sexes from 6 to 41 weeks' gestational age. There was a consistent temporal and spatial pattern of sIR in the hippocampus and cerebral neocortex. In the rostral hippocampus, sIR was first apparent in the molecular zone of the dentate gyrus at 12 weeks, followed by CA2 at 14 weeks, CA3 and CA4 at 15 to 16 weeks, and CA1 at 19 weeks; it was incomplete until 26 weeks. In frontal neocortex, sIR developed in a laminar pattern above and below the cortical plate as early as 12 weeks, around Cajal-Retzius neurons of the molecular zone at 14 weeks, surrounding pyramidal neurons of Layers 5 and 6 at 16 weeks, and at the surface of neuronal somata in Layers 2 and 4 at 22 weeks. At 33 weeks, Layers 2 and 4 still had less sIR than other layers. Uniform sIR among all cortical layers was evident at 38 weeks. Ascending probable thalamocortical axons were reactive as early as 12 weeks and were best demonstrated by 26 weeks, after which increasing sIR in the neuropil diminished the contrast. The sIR was preserved for more than 96 hours postmortem, even in severely autolytic brains. We conclude that synaptophysin is a reliable marker in human fetal brain and that sIR provides the means for objective assessment of cerebral maturation in normal brains and to enable interpretation of abnormal synaptic patterns in pathological conditions.