Molybdenum cofactor deficiency: A natural history.

Molybdenum cofactor deficiency (MoCD) includes three ultrarare autosomal recessive inborn errors of metabolism (MoCD type A [MoCD-A], MoCD-B, and MoCD-C) that cause sulfite intoxication disorders. This natural history study analyzed retrospective data for 58 living or deceased patients (MoCD-A, n = 41; MoCD-B, n = 17). MoCD genotype, survival, neuroimaging, and medical history were assessed retrospectively. Prospective biomarker data were collected for 21 living MoCD patients. The primary endpoint was survival to 1 year of age in MoCD-A patients. Of the 58 MoCD patients, 49 (MoCD-A, n = 36; MoCD-B, n = 13) had first presenting symptoms by Day 28 (neonatal onset; median: 2 and 4 days, respectively). One-year survival rates were 77.4% (overall), 71.8% (neonatal onset MoCD-A), and 76.9% (neonatal onset MoCD-B); median ages at death were 2.4, 2.4, and 2.2 years, respectively. The most common presenting symptoms in the overall population were seizures (60.3%) and feeding difficulties (53.4%). Sequelae included profound developmental delay, truncal hypotonia, limb hypertonia that evolved to spastic quadriplegia or diplegia, dysmorphic features, and acquired microcephaly. In MoCD-A and MoCD-B, plasma and urinary xanthine and S-sulfocysteine concentrations were high; urate remained below the normal reference range. MOCS1 mutation homozygosity was common. Six novel mutations were identified. MoCD is a severe neurodegenerative disorder that often manifests during the neonatal period with intractable seizures and feeding difficulties, with rapidly progressive significant neurologic disabilities and high 1-year mortality rates. Delineation of MoCD natural history supports evaluations of emerging replacement therapy with cPMP for MoCD-A, which may modify disease course for affected individuals.

The condition of volumetric and osmoregulatory function of the kidneys in toxicemia of purulent-septic genesis in patients with diabetes mellitus.

OBJECTIVE: The aim of the study is to investigate the state of volumetric and osmoregulatory function of the kidneys in diabetes complicated by the syndrome of the endogenous intoxication of purulent-septic genesis. PATIENTS AND METHODS: Materials and methods: The study group was consisted of patients with insulin-dependent diabetes mellitus with complicated syndrome of the endogenous intoxication of purulent-septic genesis (CSDI). RESULTS: Results: The starting indices of volumetric and osmoregulatory function of the kidneys in patients with INCs complicated by the endogenous intoxication of purulent-septic genesis (CEI GHG) syndrome are characterized by the values of the inhibition of the volumorregulatory (by the clearance of sodium by 11%, p <0.05) and the activation of the osmoregulatory osmotically active substances by 23%, p <0.05) renal function. The volume increasing of the extracellular space by the Ringer solution activates the volumetric and osmoregulatory function of the kidneys, respectively, in patients with NSCL at 162 ± 27.1% (Δ, p <0.05) and 138 ± 48.3% (Δ, p <0.05), and at INCS complicated CEE GHS by 260 ± 47.8% (Δ, p <0.05) and 147 ± 46.9% (Δ, p <0.05). CONCLUSION: Conclusions: The low-level isotonic loads with Ringer's solution initiate the same direction of change in indices of volumetric and osmoregulatory function of the kidneys in patients with systemic inflammatory response syndrome and diabetes mellitus with complicated endogenous intoxication syndrome of purulent-septic genesis and show dissociative hyper reactivity of the volumorregulatory function in relation to the osmoregulatory one.