The remarkable journey of one female individual with ornithine transcarbamylase deficiency diagnosed post-mortem.

Urea cycle disorders (UCDs) comprise a group of inborn errors of metabolism with impaired ammonia clearance and an incidence of ~1:35 000 individuals. First described in the 1970s, the diagnosis and management of these disorders has evolved dramatically. We report on a 59-year-old woman with a UCD who contributed to advances in the understanding and treatment of this group of disorders.

Disruption of the HIF-1 pathway in individuals with Ollier disease and Maffucci syndrome.

Ollier disease (OD) and Maffucci Syndrome (MS) are rare disorders characterized by multiple enchondromas, commonly causing bone deformities, limb length discrepancies, and pathological fractures. MS is distinguished from OD by the development of vascular anomalies. Both disorders are cancer predisposition syndromes with malignancies developing in ~50% of the individuals with OD or MS.

ATRX loss promotes immunosuppressive mechanisms in IDH1 mutant glioma.

Background: ATRX inactivation occurs with IDH1R132H and p53 mutations in over 80% of Grades II/III astrocytomas. It is believed that ATRX loss contributes to oncogenesis by dysregulating epigenetic and telomere mechanisms but effects on anti-glioma immunity have not been explored. This paper examines how ATRX loss contributes to the malignant and immunosuppressive phenotypes of IDH1R132H/p53mut glioma cells and xenografts.

Developmental features of sleep electrophysiology in family dogs.

Age-related differences in dog sleep and the age at which dogs reach adulthood as indexed by sleep electrophysiology are unknown. We assessed, in (1) a Juvenile sample (n = 60) of 2-14-month-old dogs (weight range: 4-68 kg), associations between age, sleep macrostructure, and non-rapid eye movement (NREM) EEG power spectrum, whether weight moderates associations, and (2) an extended sample (n = 91) of 2-30-months-old dogs, when sleep parameters stabilise. In Juvenile dogs, age was positively associated with time in drowsiness between 2 and 8 months, and negatively with time in rapid eye movement (REM) sleep between 2 and 6 months.

Sterol and lipid analyses identifies hypolipidemia and apolipoprotein disorders in autism associated with adaptive functioning deficits.

An improved understanding of sterol and lipid abnormalities in individuals with autism spectrum disorder (ASD) could lead to personalized treatment approaches. Toward this end, in blood, we identified reduced synthesis of cholesterol in families with ≥2 children with ASD participating with the Autism Genetic Resource Exchange (AGRE), as well as reduced amounts of high-density lipoprotein cholesterol (HDL), apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB), with 19.9% of the subjects presenting with apolipoprotein patterns similar to hypolipidemic clinical syndromes and 30% with either or both ApoA1 and ApoB less than the fifth centile.

Characterization of an Isostructural MOF Series of Imidazolate Frameworks Potsdam by Means of Sorption Experiments with Water Vapor.

Sorption measurements of water vapor on an isoreticular series of Imidazolate Frameworks Potsdam (IFP), based on penta-coordinated metal centers with secondary building units (SBUs) connected by multidentate amido-imidate-imidazolate linkers, have been carried out at 303.15 K. The isotherm shapes were analyzed in order to gain insight into material properties and compared to sorption experiments with nitrogen at 77.

Novel gene variant for congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD) syndrome.

We report a case of a 1-year and 2-month-old girl with clinical features consistent with congenital hemidysplasia with ichthyosis and limb defects syndrome. Sterol analysis from skin flakes revealed increased levels of a mono 4-alpha methyl sterol also seen in plasma as well as the presence of 4-alpha-carboxy-4-methyl-cholest-8(9)-en-3beta-ol and several keto-sterols, which are usually below the limit of detection. This sterol pattern is consistent with abnormal function of the 4-alpha-methylsterol-4-demethylase complex.

A homozygous variant in the Lamin B receptor gene LBR results in a non-lethal skeletal dysplasia without Pelger-Huët anomaly.

Lamin B receptor, a member of the sterol reductase family, is an inner nuclear membrane protein which binds lamin B proteins and is involved in the organization of heterochromatin. Mutations in LBR have been associated with a variety of disorders, such as Pelger-Huët anomaly, a benign abnormality affecting neutrophils, and Greenberg Dysplasia, a lethal condition in the perinatal period. We identified a homozygous LBR missense mutation (NM_002296.

Metabolic Stroke: A Novel Presentation in a Child with Succinic Semialdehyde Dehydrogenase Deficiency.

Succinic semialdehyde dehydrogenase (SSADH) deficiency is an autosomal recessive disorder of gamma-aminobutyric acid metabolism. Children with SSADH deficiency usually manifest with developmental delay, behavioral symptoms, language dysfunction, seizures, hypotonia, extrapyramidal symptoms, and ataxia. Diagnosis of SSADH deficiency is established by an abnormal urine organic acid pattern, including increased excretion of 4-hydroxybutyric acid and the identification of biallelic pathogenic variants in aldehyde dehydrogenase 5 family, member A 1 () gene.

Laboratory diagnosis of disorders of peroxisomal biogenesis and function: a technical standard of the American College of Medical Genetics and Genomics (ACMG).

Peroxisomal disorders are a clinically and genetically heterogeneous group of diseases caused by defects in peroxisomal biogenesis or function, usually impairing several metabolic pathways. Peroxisomal disorders are rare; however, the incidence may be underestimated due to the broad spectrum of clinical presentations. The inclusion of X-linked adrenoleukodystrophy to the Recommended Uniform Screening Panel for newborn screening programs in the United States may increase detection of this and other peroxisomal disorders.

Lamin B receptor-related disorder is associated with a spectrum of skeletal dysplasia phenotypes.

LBR (Lamin B Receptor) encodes a bifunctional protein important for cholesterol biosynthesis and heterochromatin organization on the inner nuclear membrane. Pathogenic variants in LBR are associated with marked phenotypic variability, ranging from the benign Pelger-Huët anomaly to lethal Greenberg Dysplasia. We performed trio exome sequencing (ES) on two patients with atypical variants of skeletal dysplasia and their unaffected parents.

Severe Neonatal Manifestations of Infantile Liver Failure Syndrome Type 1 Caused by Cytosolic Leucine-tRNA Synthetase Deficiency.

Background: Deleterious mutations in cytosolic leucine-tRNA synthetase (LARS) cause infantile liver failure syndrome, type 1 (ILFS1), a recently recognized, rare autosomal recessive disorder (OMIM151350). Only six families with ILFS1 have been reported in the literature. Patients with ILFS1 are typically diagnosed between 5 and 24 months of age with failure to thrive, developmental delays, encephalopathy, microcytic anemia, and chronic liver dysfunction with recurrent exacerbations following childhood illnesses.

Elevated creatinine in a patient on IVIG-therapy.

Background: Intravenous immunoglobulin (IVIG) is prepared from the plasma of hundreds of blood donors and is used in the treatment of immunodeficiencies, autoimmune conditions, infections and inflammatory conditions. IVIG formulations contain one of a number of small molecule stabilizers, including sugars, polyols, and amino acids, some of which can cause acute renal failure.

Case Report: A 61 y-old woman was treated for paraneoplastic syndrome due to small cell lung cancer in which a creatinine measurement unexpectedly increased during IVIG therapy.

Heterozygous IDH1 created by "single base editing" inhibits human astroglial cell growth by downregulating YAP.

Mutations in the isocitrate dehydrogenase 1 (IDH1) gene have been identified in a number of cancer types, including brain cancer. The Cancer Genome Atlas project has revealed that IDH1 mutations occur in 70-80% of grade II and grade III gliomas. Until recently, most of the functional studies of IDH1 mutations in cellular models have been conducted in overexpression systems with the IDH1 wild type background.

Randomized open-label trial of dextromethorphan in Rett syndrome.

Objective: To determine safety and perform a preliminary assessment of dose-dependent efficacy of dextromethorphan in normalizing electrographic spikes, clinical seizures, and behavioral and cognitive functions in girls with Rett syndrome.

Methods: We used a prospective randomized, open-label trial in fast metabolizers of dextromethorphan to examine the effect of dextromethorphan on core clinical features of Rett syndrome. Interictal spike activity and clinical seizures were determined using EEG and parent reporting.

Severe phenotype of X-linked dominant chondrodysplasia punctata.

A prenatally ascertained case representing the more severe end of the X-linked dominant chondrodysplasia punctata (CDPX2).

A placebo-controlled trial of simvastatin therapy in Smith-Lemli-Opitz syndrome.

Background: Smith-Lemli-Opitz syndrome (SLOS) is a multiple malformation/cognitive impairment syndrome characterized by the accumulation of 7-dehydrocholesterol, a precursor sterol of cholesterol. Simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor that crosses the blood-brain barrier, has been proposed for the treatment of SLOS based on in vitro and in vivo studies suggesting that simvastatin increases the expression of hypomorphic DHCR7 alleles.

Methods: Safety and efficacy of simvastatin therapy in 23 patients with mild to typical SLOS were evaluated in a randomized, double-blind, placebo-controlled trial.