Citations

Inositol 1,4,5-trisphosphate (IP3) receptor type 1 ( ITPR1 ), 2 ( ITPR2 ), and 3 ( ITPR3 ) encode the IP3 receptor (IP3R), a key player in intracellular calcium release. In four unrelated patients, we report that an identical ITPR3 de novo variant—NM_002224.3:c.7570C>T, p.Arg2524Cys—causes, through a dominant-negative effect, a complex multisystemic disorder with immunodeficiency. This leads to defective calcium homeostasis, mitochondrial malfunction, CD4 + lymphopenia, a quasi-absence of naïve CD4 + and CD8 + cells, an increase in memory cells, and a distinct TCR repertoire. The calcium defect was recapitulated in Jurkat knock-in. Site-directed mutagenesis displayed the exquisite sensitivity of Arg 2524 to any amino acid change. Despite the fact that all patients had severe immunodeficiency, they also displayed variable multisystemic involvements, including ectodermal dysplasia, Charcot-Marie-Tooth disease, short stature, and bone marrow failure. In conclusion, unlike previously reported ITPR1-3 deficiencies leading to narrow, mainly neurological phenotypes, a recurrent dominant ITPR3 variant leads to a multisystemic disease, defining a unique role for IP3R3 in the tetrameric IP3R complex.

Iodine is an essential component of thyroid hormones, which play a critical role in neurodevelopment. The iodine status of pregnant women and their newborns is not checked routinely. Extremely Low Gestational Age Newborns do not receive Iodine supplementation while on parenteral nutrition (PN). We measured urine iodine levels and thyroid function tests in 50 mother–infant dyads at birth, at 1 week, 1, 2, 3 months and near discharge. We correlated maternal and neonatal urine iodine levels with thyroid functions and measured iodine levels in milk and PN. In our study, 64% of mothers were iodine deficient at the time of delivery, their free T4 levels were 0.48 (0.41–0.54) ng/dL with normal thyroid-stimulating hormone (TSH). Iodine levels were thirty-fold higher in extremely low gestational age newborns (ELGAN) exposed to iodine comparing to full terms (p < 0.001), but this effect lasted <1 week. At 1 month of age, ELGAN on PN developed iodine deficiency (p = 0.017) and had high thyroglobulin levels of 187 (156–271) ng/mL. Iodine levels improved with enteral feeds by 2 months of age (p = 0.01). Iodine deficiency is prevalent among pregnant women and ELGAN; in particular, those on PN are at risk of hypothyroidism. Iodine supplementation during pregnancy and postnatally should be considered to avoid iodine deficiency.

Objective: 1) Characterize corrective saccades (CS) in normal controls, and 2) examine the sensitivity of the video head impulse test (vHIT) for identifying vestibular loss using both gain and CS. Study Design: Prospective combined with retrospective review. Setting: Tertiary referral center. Patients: Seventy subjects with normal vestibular function served as controls (mean age, 44.1 yr; range, 10–78) and data from 49 patients with unilateral and bilateral vestibular loss was retrospectively reviewed (mean age, 50; range, 7–81). Intervention: vHIT; individual horizontal head impulses were then analyzed in MATLAB. Main Outcome Measures: Horizontal vHIT gain, CS peak velocity, frequency, and latency. Results: There was not an age effect for CS velocity or latency, and only a weak relationship between CS frequency and age in the control group. Gain and CS latency were the only parameters affected by impulse side, demonstrating higher gain and longer latency on the right. The group with vestibular loss had significantly lower mean vHIT gain, higher mean CS frequency, higher mean CS velocity, earlier CS latency, and smaller mean CS standard deviations of the latency compared with the control group. When all factors were analyzed separately by logistic regression, vHIT gain provided the best classification (83.8%), closely followed by CS frequency (83.1%). Using a two variable approach (both gain and CS frequency) yielded the best diagnostic accuracy (overall classification = 84.6%). Conclusions: Along with gain, incorporating CS frequency in interpreting vHIT improves diagnostic accuracy. A repeatable CS (>81.89%) and/or low gain (<0.78) indicate vestibular loss.

Identifying patients who will benefit from a palliative care approach is the first critical step in integrating palliative with curative therapy. Criteria are established that identify hospitalized medical patients who are near end of life, yet there are no criteria with respect to hospitalized patients with psychiatric disorders. The records of 276 consecutive patients admitted to a dedicated inpatient psychiatric unit were reviewed to identify prognostic criteria predictive of mortality. Mortality predictors were 2 or more admissions in the past year ( P = .0114) and older age ( P = .0006). Twenty-two percent of patients met National Hospice and Palliative Care Organization noncancer criteria for dementia. Palliative care intervention should be considered when treating inpatients with psychiatric disorders, especially older patients who have a previous hospitalization or history of dementia.