Rapid improvement of skin lesions in CHILD syndrome with topical 5% simvastatin ointment.

Congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD) syndrome is a rare X-linked dominant disorder of cholesterol synthesis characterized by unilateral ichthyosiform dermatitis with ipsilateral limb hypoplasia. Recently, pathogenesis-based treatment has demonstrated improvement of skin lesions with statins by decreasing formation of cholesterol intermediates through inhibition of cholesterol synthesis. We report a 10-month-old girl who presented with unilateral scaly ptychotropic plaques, who experienced rapid, near-complete clearance with topical 5% simvastatin monotherapy twice daily.

Quantitative analysis of the natural history of prolidase deficiency: description of 17 families and systematic review of published cases.

Purpose: Prolidase deficiency is a rare inborn error of metabolism causing ulcers and other skin disorders, splenomegaly, developmental delay, and recurrent infections. Most of the literature is constituted of isolated case reports. We aim to provide a quantitative description of the natural history of the condition by describing 19 affected individuals and reviewing the literature.

Hydroxysteroid 17-Beta Dehydrogenase Type 10 Disease in Siblings.

Hydroxysteroid 17-beta dehydrogenase type 10 (HSD10) deficiency (HSD10 disease) is a rare X-linked neurodegenerative condition caused by abnormalities in the HSD17B10 gene. A total of 10 mutations have been reported in the literature since 2000. Described phenotypes include a severe neonatal or progressive infantile form with hypotonia, choreoathetosis, seizures, cardiomyopathy, neurodegeneration, and death, as well as an attenuated form with variable regression.

Association between body weight and composition and plasma 25-hydroxyvitamin D level in the Diabetes Prevention Program.

Objective: We examined associations between body weight and plasma 25-hydroxyvitamin D concentration (25OHD) in prediabetes and sought to estimate the impact of adiposity on these associations.

Methods: The study was conducted in the placebo (n = 1082) and intensive lifestyle (n = 1079) groups of the Diabetes Prevention Program (DPP), a multicenter trial to prevent type 2 diabetes in adults with prediabetes. Weight and 25OHD were measured at baseline, month 6, years 1 and 2.

Vitamin D deficiency is associated with progression of knee osteoarthritis.

Background: Knee osteoarthritis causes functional limitation and disability in the elderly. Vitamin D has biological functions on multiple knee joint structures and can play important roles in the progression of knee osteoarthritis. The metabolism of vitamin D is regulated by parathyroid hormone (PTH).

Plasma 25-hydroxyvitamin D and progression to diabetes in patients at risk for diabetes: an ancillary analysis in the Diabetes Prevention Program.

Objective: To investigate the association between vitamin D status, assessed by plasma 25-hydroxyvitamin D, and risk of incident diabetes.

Research Design And Methods: Prospective observational study with a mean follow-up of 2.7 years in the Diabetes Prevention Program (DPP), a multicenter trial comparing different strategies for prevention of diabetes in patients with prediabetes.

The syndrome of perisylvian polymicrogyria with congenital arthrogryposis.

Background: Bilateral perisylvian polymicrogyria (BPP) is a well-recognized malformation of cortical development commonly associated with epilepsy, cognitive impairment, and oromotor apraxia. Reports have suggested the association of BPP with arthrogryposis multiplex congenita. We sought to investigate the clinical, electrophysiological, and neuroradiological features of this combined syndrome to determine if there are unique features that distinguish BPP with arthrogryposis from BPP alone.

A Delphi clinical practice protocol for the management of very long chain acyl-CoA dehydrogenase deficiency.

Introduction: Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency is a disorder of oxidation of long chain fat, and can present as cardiomyopathy or fasting intolerance in the first months to years of life, or as myopathy in later childhood to adulthood. Expanded newborn screening has identified a relatively high incidence of this disorder (1:31,500), but there is a dearth of evidence-based outcomes data to guide the development of clinical practice protocols. This consensus protocol is intended to assist clinicians in the diagnosis and management of screen-positive newborns for VLCAD deficiency until evidence-based guidelines are available.

Blockade of GABA synthesis only affects neural excitability under activated conditions in rat hippocampal slices.

The primary goal of this study was to establish whether inhibition of GABA synthesis was sufficient to induce network hyperexcitability in a rat hippocampal slice model comparable to that seen with GABA receptor blockade. We used field and intracellular recordings from the CA1 region of rat hippocampal slices to determine the physiological effects of blocking GABA synthesis with the convulsant, 3-mercaptoproprionic acid (MPA). We measured the rate of synthesis of GABA and glutamate in slices using 2-13C-glucose as a label source and liquid chromatography-tandem mass spectrometry.

A Delphi-based consensus clinical practice protocol for the diagnosis and management of 3-methylcrotonyl CoA carboxylase deficiency.

3-MCC deficiency is among the most common inborn errors of metabolism identified on expanded newborn screening (1:36,000 births). However, evidence-based guidelines for diagnosis and management of this disorder are lacking. Using the traditional Delphi method, a panel of 15 experts in inborn errors of metabolism was convened to develop consensus-based clinical practice guidelines for the diagnosis and management of 3-MCC screen-positive infants and their mothers.

Validation of high-throughput methods for measuring blood urea nitrogen and urinary albumin concentrations in mice.

Chronic kidney disease is a substantial medical and economic burden. Animal models, including mice, are a crucial component of kidney disease research; however, recent studies disprove the ability of autoanalyzer methods to accurately quantify plasma creatinine levels, an established marker of kidney disease, in mice. Therefore, we validated autoanalyzer methods for measuring blood urea nitrogen (BUN) and urinary albumin concentrations, 2 common markers of kidney disease, in samples from mice.

Metabolic evaluation of the sick neonate.

Inherited metabolic diseases are rare causes of neonatal morbidity, but they are associated with significant recurrence risks for the parents. Prompt identification and treatment of an infant with an inherited metabolic disease can minimize morbidity, mortality, and lifelong developmental problems. Diagnosis often requires specialized laboratory testing, but common laboratory tests can help identify those infants needing further evaluation.

Recurrent high anion gap metabolic acidosis secondary to 5-oxoproline (pyroglutamic acid).

High anion gap metabolic acidosis in adults is a severe metabolic disorder for which the primary organic acid usually is apparent by clinical history and standard laboratory testing. We report a case of recurrent high anion gap metabolic acidosis in a 48-year-old man who initially presented with anorexia and malaise. Physical examination was unrevealing.

Assays for measuring extracellular GABA levels and cell migration rate in acute slices.

The postnatal subventricular zone (SVZ) contains the largest pool of dividing and migrating neural precursors in the adult rodent brain. Neuronal precursors migrate throughout the SVZ and along the rostral migratory stream (RMS) towards the olfactory bulb where they differentiate into interneurons. To facilitate the investigation of cell migration in the SVZ and RMS, an inexpensive migration assay was developed for use in acute brain slices.

New KIT mutations in patients with piebaldism.

Background: Piebaldism is an autosomal dominantly inherited disorder characterized by congenital leukoderma, typically on the forehead, abdomen, and knees. The leukoderma is usually stable throughout life. KIT mutations have been demonstrated in about 75% of patients with piebaldism.

Infantile hypermethioninemia and hyperhomocysteinemia due to high methionine intake: a diagnostic trap.

Studies were carried out to identify the cause of combined severe hypermethioninemia and moderate hyperhomocysteinemia in a cluster of 10 infants ascertained between 1999 and early 2001. Although several were thought initially to have cystathionine beta-synthase (CBS) deficiency and treated accordingly, CBS deficiency and other known genetic causes of hypermethioninemia were ruled out by assay of CBS activity in fibroblasts of four patients and by assays of plasma cystathionine and S-adenosylmethionine. Retrospective data on dietary methionine intakes and plasma concentrations of methionine and related metabolites established that the hypermethioninemia in nine of the 10 babies was related to ingestion of an infant protein hydrolysate formula, the methionine content of which had been increased from May 1998 to February 2001.