Search Results (3)

Background: In type 2 diabetes mellitus (T2DM), bone and microvascular complications may be linked. Methods: The University of California Davis (UCD) polygenic T2DM and Sprague Dawley healthy control (CTL) rats (N = 48) were divided equally into diabetic and age-matched groups: (1) pre-diabetes, (2) diabetes onset, (3) early-stage T2DM, and (4) late-stage T2DM. Body mass, HbA1c, fasted blood glucose and femoral and tibial lengths were measured. Bones were scanned (μCT; 15 µm) to assess trabecular microarchitecture and density and mid-shaft cortical thickness (Ct.Th, µm), density and porosity. Ossified vessel volume (OsVV, %) and thickness (OsV.Th, µm) were also analyzed. A GLM determined significance at p < 0.05. Body mass and HbA1c were higher (p < 0.05) in all T2DM groups and blood glucose became elevated (p < 0.05) in early-stage T2DM and late-stage T2DM. Results: Tibiae and femora were longer (p < 0.05) with diabetes. Tibial bone volume was lower (p < 0.05) in pre-diabetes (4 ± 1% vs. CTL, 9 ± 2%) and late-stage T2DM (5 ± 2% vs. CTL, 8 ± 2%), and femoral bone volume was lower (p < 0.05) in pre-diabetes (7 ± 1% vs. 12 ± 4%). Cortical density (tibia) was lower (p < 0.05) in pre-diabetes and early-stage T2DM. Trabecular density in the femur was lower (p < 0.05) in all T2DM groups and cortical density was reduced (p < 0.05) in pre-diabetes, diabetes onset, and late-stage T2DM. OsVV in both bones were lower (p < 0.05) during early-stage T2DM. Tibial OsV.Th was higher (p < 0.05) in pre-diabetes (69 ± 14 µm vs. CTL, 56 ± 13 µm) and late-stage T2DM (80 ± 10 µm vs. CTL, 59 ± 13 µm) and higher (p < 0.05) in the femur at diabetes onset (58 ± 14 µm vs. CTL, 40 ± 10 µm). Conclusions: Trabecular and cortical bone varied as diabetes progressed, and the thicker ossified vessels may represent microangiopathy. Full article

Background/Objectives: The present study updates the Spanish registry of patients with urea cycle disorders (UCD), originally established in 2013, to provide comprehensive epidemiological data and evaluate the impact of therapeutic strategies and newborn screening (NBS) on clinical outcomes. Methods: This retrospective, multicenter study focuses on 255 Spanish UCD patients. It includes all living and deceased cases up to February 2024, analyzing demographic, clinical, and biochemical variables. Results: The incidence of UCD in Spain over the past decade was 1:36,063 births. The most common defects were ornithine transcarbamylase deficiency (OTCD) and argininosuccinate synthetase deficiency. Early-onset (EO) cases comprised 32.7%, and 10.6% were diagnosed through NBS. Global mortality was 14.9%, higher in carbamoylphosphate synthetase 1 deficiency (36.8%) and male OTCD patients (32.1%) compared to other defects (p = 0.013). EO cases presented a higher mortality rate (35.8%) than late-onset (LO) cases (7.1%) (p < 0.0001). The median ammonia level in deceased patients was higher at 1058 µmol/L (IQR 410–1793) than in survivors at 294 µmol/L (IQR 71–494) (p < 0.0001). Diagnosis through NBS improved survival and reduced neurological impairment compared to symptomatic diagnosis. Neurological impairment occurred in 44% of patients, with worse neurological outcomes observed in patients with argininosuccinate lyase deficiency, arginase 1 deficiency, hyperornithinemia-hyperammonemia-homocitrullinuria, EO presentations, pre-2014 diagnosis, and patients with higher levels of ammonia at diagnosis. Among transplanted patients (20.6%), survival was 95.2%, with no significant neurological differences compared to non-transplanted patients. Conclusions: This updated analysis highlights the positive impact of NBS and advanced treatments on mortality and neurologic outcomes. Persistent neurological challenges underscore the need for further therapeutic strategies. Full article

N-acetylglutamate synthase deficiency (NAGSD) is an extremely rare urea cycle disorder (UCD) with few adult cases so far described. Diagnosis of late-onset presentations is difficult and delayed treatment may increase the risk of severe hyperammonemia. We describe a 52-year-old woman with recurrent headaches who experienced an acute onset of NAGSD. As very few papers focus on headaches in UCDs, we also report a literature review of types and pathophysiologic mechanisms of UCD-related headaches. In our case, headaches had been present since puberty (3–4 days a week) and were often accompanied by nausea, vomiting, or behavioural changes. Despite three previous episodes of altered consciousness, ammonia was measured for the first time at 52 years and levels were increased. Identification of the new homozygous c.344C>T (p.Ala115Val) NAGS variant allowed the definite diagnosis of NAGSD. Bioinformatic analysis suggested that an order/disorder alteration of the mutated form could affect the arginine-binding site, resulting in poor enzyme activation and late-onset presentation. After optimized treatment for NAGSD, ammonia and amino acid levels were constantly normal and prevented other headache bouts. The manuscript underlies that headache may be the presenting symptom of UCDs and provides clues for the rapid diagnosis and treatment of late-onset NAGSD. Full article