Critical sample collection delayed? Urine organic acid analysis can still save the day! A new case of HMG-CoA synthase deficiency.

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase (mHS) deficiency is an autosomal recessive disorder of ketone body synthesis caused by biallelic pathogenic variants in HMGCS2. Clinical symptoms are precipitated by prolonged fasting and/or intercurrent illness with onset before the first year of life. Clinically, patients may present with hypo-/ non-ketotic hypoglycemia, metabolic acidosis, hyperammonemia, lethargy, hepatomegaly, and encephalopathy. During periods of decompensation, elevations of 4-hydroxy-6-methyl-2-pyrone (4-HMP), several hydroxylated hexanoic and hexenoic acid species, and medium-chain dicarboxylic acids in the absence of significant ketonuria may be observed in the urine organic acid profile. Abnormalities may also be observed in plasma which includes elevated acetylcarnitine (C2) and 3-hydroxybutyryl/3-hydroxyisobutyryl (C4-OH) carnitine. We report a patient who presented to the ED at 13 months of age with an undetectable point-of-care blood glucose level. Continuous infusion of dextrose-containing intravenous (IV) fluids were required to correct the hypoglycemia and routine chemistries were notable for an anion gap metabolic acidosis, transaminasemia, and elevated creatine kinase and lactate dehydrogenase. Urine and blood ketones were undetectable. Qualitative assessment of urine organic acids collected ∼46 and âˆ¼ 99 h post-admission were significant for mild elevations of 4-HMP and hydroxy-hexanoic and hydroxy-hexenoic acid species with a notable absence of ketones. Previously, biochemical abnormalities in urine have been shown to normalize in as few as 27 h after treatment giving providers a narrow window with which to obtain a critical sample. Direct communication of laboratory findings to the ordering provider guided the molecular testing and assisted in results interpretation to confirm the molecular diagnosis. Our case emphasizes the importance of collecting samples for biochemical analysis even if the critical period has been missed and acute metabolic decompensation seems to be resolved, as residual abnormalities observed in our patient greatly narrowed the differential diagnosis.

Unmasking the cis-Stilbene Phantom State via Vacuum Ultraviolet Time-Resolved Photoelectron Spectroscopy and Ab Initio Multiple Spawning.

We present the first vacuum ultraviolet time-resolved photoelectron spectroscopy (VUV-TRPES) study of photoisomerization dynamics in the paradigmatic molecule cis-stilbene. A key reaction intermediate in its dynamics, known as the phantom state, has often been invoked but never directly detected in the gas phase. We report direct spectral signatures of the phantom state in isolated cis-stilbene, observed and characterized through a combination of VUV-TRPES and ab initio multiple spawning (AIMS) nonadiabatic dynamics simulations of the channel-resolved observable. The high VUV probe photon energy tracks the complete excited-state dynamics via multiple photoionization channels, from initial excitation to its return to the "hot" ground state. The TRPES was compared with AIMS simulations of the dynamics from initial excitation, to the phantom-state intermediate (an S1 minimum), through to the ultimate electronic decay to the ground state. This combination revealed the unique spectral signatures and time-dependent dynamics of the phantom-state intermediate, permitting us to report here its direct observation.

Nonadiabatic Dynamics of Photoexcited cis-Stilbene Using Ab Initio Multiple Spawning.

The photochemistry of cis-stilbene proceeds through two pathways: cis-trans isomerization and ring closure to 4a,4b-dihydrophenanthrene (DHP). Despite serving for many decades as a model system for photoisomerization, the photodynamics of cis-stilbene is still not fully understood. We use ab initio multiple spawning on a SA-2-CASSCF(2,2) potential energy surface to simulate the nonadiabatic dynamics of isolated cis-stilbene. We find the cyclization (to DHP and cis-stilbene) and isomerization (to trans- and cis-stilbene) reaction coordinates to be orthogonal; branching between the two pathways is determined on the S1 excited state within 150 fs of photoexcitation. Trajectory basis functions (TBFs) undergoing cyclization decay rapidly to the ground state in 250 fs, while TBFs moving along the isomerization coordinate remain on the excited state longer, with the majority decaying between 300 and 500 fs. We observe three avoided crossing regions in the dynamics: two along the isomerization coordinate (displaying pyramidalization and migration of an ethylenic hydrogen or phenyl group), and one DHP-like conical intersection along the cyclization coordinate. The isomeric form of the vibrationally hot photoproducts (as determined by measurement 2 ps after photoexcitation) is determined within less than 50 fs of decay to the ground state mediated by passage through a conical intersection. Excess vibrational energy of ground state cis- and trans-stilbene is channelled into phenyl torsions (with mostly opposing directionality). Our simulations are validated by direct comparison to experiment for the absorption spectrum, branching ratio of the three photoproducts (44:52:4 cis-stilbene:trans-stilbene:DHP), and excited state lifetime (520 ± 40 fs).

Cornstarch requirements of the adult glycogen storage disease Ia population: A retrospective review.

Cornstarch has been the primary treatment for glycogen storage disease type Ia (GSD Ia) for over 35 years. When cornstarch was first described as a treatment, few people survived beyond early childhood. As the prognosis for this population has improved, the need to ensure appropriate cornstarch dosing for different age groups has become imperative. Records from 115 patients (10-62 years of age) with GSD Ia evaluated at our center between 2015 and 2017 were reviewed. Data collected included weight, age, genetic mutation, amount and frequency of cornstarch doses, body mass index, gender, 24-hour glucose and lactate concentrations, and biochemical markers of metabolic control. The data demonstrate that adult treatment needs vary greatly from younger age groups, and the required cornstarch support decreases with age (P < .001). The required number of doses, however, did not change with a mean of six doses (range 4-8) daily in all age groups. General laboratory findings across time demonstrate that significantly reducing the amount of starch required to maintain euglycemia with aging can be done without sacrificing metabolic control. Carbohydrate requirements decrease with aging, and older patients were found to require less cornstarch. Failure to lower the cornstarch doses contributes to over-treatment in adults with GSD Ia. Not only does this lead to worsening hepatomegaly and excessive weight gain, but over-treatment contributes to relative hyperinsulinism and rebound hypoglycemia. This knowledge is essential in designing nutritional therapies for the aging GSD population.

Influence of Molecular Shape on Solid-State Packing in Disordered PC61BM and PC71BM Fullerenes.

Molecular and polymer packings in pure and mixed domains and at interfacial regions play an important role in the photoconversion processes occurring within bulk heterojunction organic solar cells (OSCs). Here, molecular dynamics simulations are used to investigate molecular packing in disordered (amorphous) phenyl-C70-butyric acid-methyl ester (PC71BM) and its C60 analogue (PC61BM), the two most widely used molecular-based electron-accepting materials in OSCs. The more ellipsoidal character of PC71BM leads to different molecular packings and phase transitions when compared to the more spherical PC61BM. Though electronic structure calculations indicate that the average intermolecular electronic couplings are comparable for the two systems, the electronic couplings as a function of orientation reveal important variations. Overall, this work highlights a series of intrinsic differences between PC71BM and PC61BM that should be considered for a detailed interpretation and modeling of the photoconversion process in OSCs where these materials are used.