A Case Report of Hypoglycemia and Hypogammaglobulinemia: DAVID syndrome in a patient with a novel NFKB2 mutation.
journal of clinical endocrinology and metabolism
DAVID syndrome (Deficient Anterior pituitary with Variable Immune Deficiency) is a rare disorder in which children present with symptomatic ACTH deficiency preceded by hypogammaglobulinemia from B-cell dysfunction with recurrent infections, termed common variable immunodeficiency (CVID). Subsequent whole exome sequencing studies have revealed germline heterozygous C-terminal mutations of NFKB2 as either a cause of DAVID syndrome or of CVID without clinical hypopituitarism. However, to the best of our knowledge there have been no cases in which the endocrinopathy has presented in the absence of a prior clinical history of CVID.A previously healthy 7 year-old boy with no history of clinical immunodeficiency, presented with profound hypoglycemia and seizures. He was found to have secondary adrenal insufficiency and was started on glucocorticoid replacement. An evaluation for autoimmune disease, including for anti-pituitary antibodies, was negative. Evaluation unexpectedly revealed hypogammaglobulinemia (decreased IgG, IgM, and IgA). He had moderately reduced serotype-specific IgG responses following pneumococcal polysaccharide vaccine. Subsequently, he was found to have growth hormone (GH) deficiency. Six years after initial presentation, whole exome sequencing revealed a novel de novo heterozygous NFKB2 missense mutation c.2596A>C (p.Ser866Arg) in the C-terminal region predicted to abrogate the processing of the p100 NFKB2 protein to its active p52 form.Isolated early-onset ACTH deficiency is rare and C-terminal region NFKB2 mutations should be considered as an etiology even in the absence of a clinical history of CVID. Early immunologic evaluation is indicated in the diagnosis and management of isolated ACTH deficiency.
View details for DOI 10.1210/jc.2017-00341
View details for PubMedID 28472507
- Clinical Use of Continuous Glucose Monitoring in Pediatrics. Diabetes technology & therapeutics 2017; 19 (S2): S37-S43
- An unusual cause of hyperglycemia JOURNAL OF POSTGRADUATE MEDICINE 2011; 57 (4): 343–46
Amyloid-beta and Glucose Metabolism in Alzheimer's Disease
JOURNAL OF ALZHEIMERS DISEASE
2011; 26: 105-116
This study used PET with the amyloid-β (Aβ) imaging agent 11 C Pittsburgh Compound-B (PIB) and the glucose metabolic tracer 18F-fluorodeoxyglucose (FDG) to map the relationship of Aβ deposition to regional glucose metabolism in Alzheimer's disease (AD). Comparison of 13 AD patients' FDG scans with 11 healthy controls confirmed a typical temporo-parietal hypometabolic pattern in AD. In contrast, PIB distribution-volume-ratios showed a distinct pattern of specific tracer retention in fronto-temporo-parietal regions and striatum in AD with peaks in left frontal cortex, precuneus, temporal cortex, striatum and right posterior cingulate. There were no region-to-region or within region correlations between FDG and PIB uptake in PIB positive AD patients but when the impact of Aβ load on glucose metabolism was assessed via probabilistic maps, increased amyloid burden was coupled with decreased metabolism in temporo-parietal regions and the posterior cingulate. However, importantly, severe Aβ burden was not associated with comparable metabolic decreases in large parts of the frontal lobes, the striatum and the thalamus.
View details for DOI 10.3233/JAD-2011-0066
View details for Web of Science ID 000297842800008
View details for PubMedID 21971455
- Amyloid-beta and Glucose Metabolism in Alzheimer's Disease HANDBOOK OF IMAGING THE ALZHEIMER BRAIN 2011; 2: 235–46
Striatal Dopamine and Working Memory
2009; 19 (2): 445-454
Recent studies have emphasized the importance of dopamine projections to the prefrontal cortex (PFC) for working memory (WM) function, although this system has rarely been studied in humans in vivo. However, dopamine and PFC activity can be directly measured with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), respectively. In this study, we examined WM capacity, dopamine, and PFC function in healthy older participants in order to test the hypothesis that there is a relationship between these 3 factors. We used the PET tracer 6-[18F]fluoro-L-m-tyrosine to measure dopamine synthesis capacity in the striatum (caudate, putamen), and event-related fMRI to measure brain activation during different epochs (cue, delay, probe) of a WM task. Caudate (but not putamen) dopamine correlated positively with WM capacity, whereas putamen (but not caudate) dopamine correlated positively with motor speed. In addition, delay-related fMRI activation in a left inferior prefrontal region was related to both caudate dopamine and task accuracy, suggesting that this may be a critical site for the integration of WM maintenance processes. These results provide new evidence that striatal dopaminergic function is related to PFC-dependent functions, particularly brain activation and behavioral performance during WM tasks.
View details for DOI 10.1093/cercor/bhn095
View details for Web of Science ID 000262518800019
View details for PubMedID 18550595
View details for PubMedCentralID PMC2733326
A beta Amyloid and Glucose Metabolism in Three Variants of Primary Progressive Aphasia
ANNALS OF NEUROLOGY
2008; 64 (4): 388-401
Alzheimer's disease (AD) is found at autopsy in up to one third of patients with primary progressive aphasia (PPA), but clinical features that predict AD pathology in PPA are not well defined. We studied the relationships between language presentation, Abeta amyloidosis, and glucose metabolism in three PPA variants using [11C]-Pittsburgh compound B ([11C]PIB) and [18F]-labeled fluorodeoxyglucose positron emission tomography ([18F]FDG-PET).Patients meeting PPA criteria (N = 15) were classified as logopenic aphasia (LPA), progressive nonfluent aphasia (PNFA), or semantic dementia (SD) based on language testing. [11C]PIB distribution volume ratios were calculated using Logan graphical analysis (cerebellar reference). [18F]FDG images were normalized to pons. Partial volume correction was applied.Elevated cortical PIB (by visual inspection) was more common in LPA (4/4 patients) than in PNFA (1/6) and SD (1/5) (p < 0.02). In PIB-positive PPA, PIB uptake was diffuse and indistinguishable from the pattern in matched AD patients (n = 10). FDG patterns were focal and varied by PPA subtype, with left temporoparietal hypometabolism in LPA, left frontal hypometabolism in PNFA, and left anterior temporal hypometabolism in SD. FDG uptake was significant asymmetric (favoring left hypometabolism) in PPA (p < 0.005) but not in AD.LPA is associated with Abeta amyloidosis, suggesting that subclassification of PPA based on language features can help predict the likelihood of AD pathology. Language phenotype in PPA is closely related to metabolic changes that are focal and anatomically distinct between subtypes, but not to amyloid deposition patterns that are diffuse and similar to AD.
View details for DOI 10.1002/ana.21451
View details for Web of Science ID 000260845000007
View details for PubMedID 18991338
View details for PubMedCentralID PMC2648510