Sleep quality in children with hepatic glycogen storage diseases, a prospective observational pilot study.

Background: Hepatic glycogen storage diseases (GSDs) are characterised by enzyme defects affecting liver glycogen metabolism, where carbohydrate supplementation to prevent overnight hypoglycaemia is common. Concerns around sleep quality in hepatic GSDs relate to emerging evidence that overnight dysglycaemia impacts sleep quality.

Methods: This prospective observational study reported sleep quality and duration in children with hepatic GSDs over 7 days utilising: actigraphy (Actiwatch 2 by Phillips Respironics), sleep diaries, proxy reported age-appropriate sleep and quality-of-life (QoL) questionnaires, in the context of nocturnal glycaemic profiles continuous glucose monitor (CGM, Dexcom G6) and nocturnal dietary management strategies.

Histologically atypical case of Gaucher disease type 1.

This report presents a case of childhood Gaucher disease type 1, a rare inherited metabolic disorder. Although the clinical symptoms were classical, the histological findings in this case were atypical and initially led to diagnostic uncertainty. The pathognomonic histological finding on bone marrow is Gaucher cells, which are lipid-engorged phagocytes secondary to the accumulation of glucosylceramide.

Interstitial lung disease and pancreatic exocrine insufficiency in CADDS: Phenotypic expansion and literature review.

Contiguous / deletion syndrome (CADDS) is a rare deletion syndrome involving two contiguous genes on Xq28, and (formerly known as ). Only nine individuals with this diagnosis have been reported in the medical literature to date. Intragenic loss-of-function variants in cause the deafness, dystonia, and cerebral hypomyelination syndrome (DDCH).

A serendipitous journey to a promoter variant: The c.-106C>A variant and its role in late-onset ornithine transcarbamylase deficiency.

Ornithine transcarbamylase deficiency (OTCD) is an X-linked urea cycle disorder characterised by reduced or absent OTC enzyme activity, resulting in the accumulation of neurotoxic ammonia. Approximately 80%-90% of the causative variants are identified by Sanger sequencing or multiplex ligation-dependent probe amplification (MLPA) of the gene. A 23-year-old male with biochemical evidence of OTCD was referred for molecular analysis.

Understanding the role of SGLT2 inhibitors in glycogen storage disease type Ib: the experience of one UK centre.

Background: Glycogen storage disease type Ib (GSD Ib) is a severe disorder of carbohydrate metabolism due to bi-allelic variants in SLC37A4. It is associated with neutropaenia and neutrophil dysfunction, which has recently been attributed to the accumulation of 1,5-anhydroglucitol-6-phosphate (1,5AG6P) within neutrophils. Treatment with sodium-glucose co-transporter-2 (SGLT2) inhibitors, such as empagliflozin, is a novel therapy that reduces 1,5-anhydroglucitol (1,5AG) in plasma.

Efficacy and safety of empagliflozin in glycogen storage disease type Ib: Data from an international questionnaire.

Purpose: This paper aims to report collective information on safety and efficacy of empagliflozin drug repurposing in individuals with glycogen storage disease type Ib (GSD Ib).

Methods: This is an international retrospective questionnaire study on the safety and efficacy of empagliflozin use for management of neutropenia/neutrophil dysfunction in patients with GSD Ib, conducted among the respective health care providers from 24 countries across the globe.

Results: Clinical data from 112 individuals with GSD Ib were evaluated, representing a total of 94 treatment years.

Ethylmalonic encephalopathy masquerading as meningococcemia.

Ethylmalonic encephalopathy (MIM #602473) is a rare autosomal recessive metabolic condition caused by biallelic variants in (MIM #608451), characterized by global developmental delay, infantile hypotonia, seizures, and microvascular damage. The microvascular changes result in a pattern of relapsing spontaneous diffuse petechiae and purpura, positional acrocyanosis, and pedal edema, hemorrhagic suffusions of mucous membranes, and chronic diarrhea. Here, we describe an instructive case in which ethylmalonic encephalopathy masqueraded as meningococcal septicemia and shock.

The natural history of glycogen storage disease type Ib in England: A multisite survey.

Glycogen storage disease type Ib (GSDIb) is characterized by hepatomegaly and fasting hypoglycaemia as well as neutropaenia and recurrent infections. We conducted a retrospective observational study on a cohort of patients with GSDIb across England. A total of 35 patients, with a median age of 9.

New insights into carnitine-acylcarnitine translocase deficiency from 23 cases: Management challenges and potential therapeutic approaches.

Carnitine acyl-carnitine translocase deficiency (CACTD) is a rare autosomal recessive disorder of mitochondrial long-chain fatty-acid transport. Most patients present in the first 2 days of life, with hypoketotic hypoglycaemia, hyperammonaemia, cardiomyopathy or arrhythmia, hepatomegaly and elevated liver enzymes. Multi-centre international retrospective chart review of clinical presentation, biochemistry, treatment modalities including diet, subsequent complications, and mode of death of all patients.

Pathogenic variants in glutamyl-tRNA amidotransferase subunits cause a lethal mitochondrial cardiomyopathy disorder.

Mitochondrial protein synthesis requires charging mt-tRNAs with their cognate amino acids by mitochondrial aminoacyl-tRNA synthetases, with the exception of glutaminyl mt-tRNA (mt-tRNA). mt-tRNA is indirectly charged by a transamidation reaction involving the GatCAB aminoacyl-tRNA amidotransferase complex. Defects involving the mitochondrial protein synthesis machinery cause a broad spectrum of disorders, with often fatal outcome.

Approach to evaluation of fever in ambulatory cancer patients receiving chemotherapy: A systematic review.

Purpose: To define the optimal model of care for patients receiving outpatient chemotherapy who experience a fever. Fever is a common symptom in patients receiving chemotherapy, but the approach to evaluation of fever is not standardized.

Methods: We conducted a search for existing guidelines and a systematic review of the primary literature from database inception to November 2015.

Approach to fever assessment in ambulatory cancer patients receiving chemotherapy: a clinical practice guideline.

Background: This guideline was prepared by the Fever Assessment Guideline Development Group, a group organized by the Program in Evidence-Based Care at the request of the Cancer Care Ontario Systemic Treatment Program. The mandate was to develop a standardized approach (in terms of definitions, information, and education) for the assessment of fever in cancer patients receiving chemotherapy.

Methods: The guideline development methods included a search for existing guidelines, literature searches in medline and embase for systematic reviews and primary studies, internal review by content and methodology experts, and external review by targeted experts and intended users.

The falciform ligament in the echocardiographic diagnosis of ascites.

Objective: The purpose of this study was to show that the falciform ligament (FL) is an important finding on transthoracic echocardiography (TTE) in patients with ascites.

Background: It is difficult to determine the cause of echo-free spaces around the heart. When an echo-free space is seen anterior to the right ventricle, the identification of the FL helps to distinguish ascites from pericardial effusions, pleural effusions, and pericardial cysts.

Percutaneous retrieval of a Wallstent from the pulmonary artery following stent migration from the iliac vein.

Wallstents are being used increasingly in conjunction with balloon dilatation for treatment of iliac vein stenosis. Stent misplacement or migration is a complication of the procedure, and may be symptomatic and warrant repositioning or removal. We report the case of a patient whose iliac vein stenosis was managed with two overlapping Wallstents and was complicated by embolization of one stent into the right ventricle (RV) and the other to the pulmonary artery (PA).

Nocardial infection in a renal transplant recipient on tacrolimus and mycophenolate mofetil.

Infection with Nocardia spp. is an uncommon but important cause of morbidity and mortality in organ transplant recipients. Cotrimoxazole prophylaxis against urinary tract infection and Pneumocystis carinii pneumonia in these patients usually prevents nocardial infection also.

Acute infarction, intracoronary thrombolysis, and primary PTCA in pregnancy.

Acute myocardial infarction has an incidence in pregnancy of 1 in 10,000, with a mortality ranging from 37-50%. Mortality is increased if the infarct occurs in the third trimester, if the patient is under age 35 yr, if she delivers within 2 wk of her infarct, and if she has a cesarean section. We present a case involving all four prognostically poor factors.

Sensitization of adenylyl cyclase by P2 purinergic and M5 muscarinic receptor agonists in L cells.

Many hormones have been shown to activate phospholipase C, which results in the hydrolysis of membrane polyphosphoinositides, such as phosphatidylinositol 4,5-bisphosphate (PIP2). Two second messengers are known to be produced by PIP2 hydrolysis, 1,2-diacylglycerol, an endogenous activator of a family of enzymes called protein kinase C (PKCs), and inositol 1,4,5-trisphosphate, which raises free levels of intracellular Ca2+. Treatment of various cells with 4 beta-phorbol 12-myristate 13-acetate (PMA), a specific exogenous activator of PKCs, causes an enhancement or sensitization of adenylyl cyclase activities.

Na(+)-independent Cl(-)-HCO3- exchange in sarcolemmal vesicles from vascular smooth muscle.

Intracellular pH (pHin) affects vascular smooth muscle function, but the mechanisms that control pHin in this tissue are not well understood. These studies were performed to determine whether sarcolemmal vesicles from bovine superior mesenteric artery (SMA) contain a Na(+)-independent Cl(-)-HCO3- exchanger and, if so, to determine its sensitivity to membrane voltage and inhibitors. 36Cl- was taken up by vesicles into an osmotically active intravesicular space.

Na(+)-H+ and Na(+)-dependent Cl(-)-HCO3- exchange control pHi in vascular smooth muscle.

The mechanisms that control intracellular pH (pHi) in vascular smooth muscle are not fully understood. These studies were performed to determine the identity and relative importance of the sarcolemmal transport systems that mediate net acid efflux in primary cultured vascular smooth muscle cells from canine femoral artery. In HEPES- or HCO3(-)-buffered physiological salt solution (HEPES-PSS, HCO3(-)-PSS), recovery from an acute acid load was totally dependent on external Na+.

The role of high levels of dietary fat in 7,12-dimethylbenzanthracene-induced mouse mammary tumorigenesis: lack of an effect on lipid peroxidation.

The effects of dietary fat on 7,12-dimethylbenzanthracene (DMBA)-induced mammary tumorigenesis were examined in BALB/c female mice. In the first experiment, BALB/c mice were treated with a total dose of 1, 3, or 6 mg DMBA to induce mammary tumors. One week after the last dose of DMBA, the mice were placed on a 5% (LF) or 20% (HF) corn oil semi-purified diet.

Selenium depletion in burn patients.

Victims of major burns may be at risk for selenium (Se) depletion because increased postinjury nutrient needs are often met by total parental nutrition and tube feedings which contain little Se. This study compared Se status of 17 burn patients and 191 healthy control subjects. Se intake of burn patients was lower than the intake of control subjects when total parenteral nutrition or tube feedings were used as primary nutrient sources but was comparable to the control intake when burn patients consumed oral diets.