Browsing by Author "Roberts, M."

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    8669 Characteristics Of Adults with Autosomal Dominant Hypocalcemia Type 1 (ADH1) Enrolled In The CLARIFY Disease Monitoring Study
    (Oxford University Press, 2024-10-05) Ing, S. W.; Harmatz, P.; Mora, S.; Imel, E. A.; Tebben, P. J.; Warren, M. L.; Ma, N.; Khan, A. A.; Palermo, A.; Decallonne, B.; Lemoine, S.; Mantovani, G.; Linglart, A.; Wasserman, H.; Barbosa, A. P.; Cardot-Bauters, C.; Roberts, M.; Mathew, A.; Adler, S.; Zillikens, M. C.; Clifton-Bligh, R. J.; Rejnmark, L.; Medicine, School of Medicine
    Autosomal dominant hypocalcemia type 1 (ADH1), caused by gain-of-function calcium-sensing receptor gene (CASR) variants, is characterized by low parathyroid hormone (PTH) concentrations, hypocalcemia, hypercalciuria, hyperphosphatemia and hypomagnesemia. While a rare disease, ADH1 is one of the more frequently identified causes of genetic hypoparathyroidism. Conventional therapy includes calcium (Ca) and/or active vitamin D, but this regimen incompletely corrects the hypocalcemia and is associated with persistent hypercalciuria, which may result in renal complications including nephrocalcinosis (NC), nephrolithiasis (NL), and chronic kidney disease (CKD). The CLARIFY disease monitoring study [NCT05227287] is a global, multicenter, longitudinal study to understand disease burden, management, and progression in children and adults with ADH1 over a 5-year period. Here we report data on the characteristics of adult participants at study entry. As of November 2023, 45 adults (≥18 years) with ADH1 were enrolled, with a mean±SD age of 42.1±16.5 years (range 18-80). The mean±SD age of a hypocalcemia diagnosis was 19.1±19.1 years, while the mean±SD age for a diagnosis of ADH1 was 28.2±20.6 years. As reported on medical history, in decreasing order of prevalence, 36% (16) had NC, 22% (10) had intracranial calcifications, 11% (5) had history of seizures, 11% (5) had CKD, 9% (4) had cataracts, 7% (3) had NL, and 4% (2) had undergone renal transplant. Treatment data were available for 43 participants and included the following: 74% (32) Ca and active vitamin D, 9% (4) Ca alone, 9% (4) active vitamin D alone, 37% (16) magnesium, 33% (14) thiazide diuretics, 26% (11) potassium, 7% (3) phosphate binder, 7% (3) PTH, and 5% (2) no treatment. Mean±SD fasting values collected prior to conventional therapy dose are presented. PTH concentrations (10.1±8.2 pg/mL [nl 15-65]) and albumin-corrected calcium ([cCa]=7.5±1.0 mg/dL [nl 8.5-10.5]) were low. Despite the low mean cCa, the mean 24-hr urine calcium was elevated (268±183 mg/d, [nl <250 women, <300 men]). Blood phosphate was 4.8±0.8 mg/dL [nl 2.5-4.8] while blood magnesium was 1.8±0.2 mg/dL [nl 1.8-2.4]. 25-OH vitamin D was 35.0±13.5 ng/mL [nl 30-80]. Renal function as assessed by CKD-EPIcr_R showed eGFR of 86±23 mL/min/1.73m² (range 36-123). This study represents the largest cohort of adults with ADH1 described to date. These data highlight variability in therapeutic approaches in a real-world setting with some participants receiving up to 6 different medications/supplements. Despite being followed in expert centers, and treated with available therapies, patients on average have low cCa with relatively high 24-hr urine calcium excretion. The CLARIFY study provides an opportunity to better understand the progression and burden of disease in participants with ADH1.
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    Middle to Late Pleistocene stability of the central East Antarctic Ice Sheet at the head of Law Glacier
    (GSA, 2017-08) Kaplan, M. R.; Licht, Kathy J.; Winckler, G.; Schaefer, J. M.; Bader, Nicole; Mathieson, C.; Roberts, M.; Kassab, Christine M.; Schwartz, R.; Graly, Joseph A.; Earth Sciences, School of Science
    Past behavior of outlet glaciers draining the East Antarctic Ice Sheet (EAIS) remains unresolved prior to Marine Isotope Stage 2 (MIS2). Study of blue ice moraines provides a relatively untapped approach to understand former EAIS activity. We focus on a blue ice moraine near Mount Achernar in the central Transantarctic Mountains, at the edge of the polar plateau. The well-preserved moraine consists of quasi-continuous or hummocky sediment ridges that form on top of upward-flowing, sublimating ice along the margin of Law Glacier. 10Be, 26Al, and 3He cosmogenic nuclide ages on boulders from the ridges are coherent and in general are progressively older with distance from the relatively clean ice of the Law Glacier margin. Moraines closest to the Law Glacier margin postdate MIS2; farther away, they date to the last glacial cycle, and with more distance they are hundreds of thousands of years old. We conclude that cosmogenic dating of some blue ice moraines can provide age limits for changes at the heads of outlet glaciers that drain the central East Antarctic Ice Sheet, including prior to MIS2. Furthermore, the geomorphological, cosmogenic nuclide, and sedimentological evidence imply that the East Antarctic polar plateau adjacent to the central Transantarctic Mountains has been relatively stable for at least 200 k.y.