ALG13-CDG in a male with seizures, normal cognitive development, and normal transferrin isoelectric focusing.

ALG13-CDG has been recently discovered as a disorder of severe developmental, intellectual and speech disability, microcephaly, visual abnormalities, seizures, hepatomegaly, coagulation abnormalities, and abnormal serumtransferrin isoelectric focusing in serum. A male with seizures, delayed motor, and speech development, but normal cognition carried a hemizygous, predicted pathogenic ALG13 variant (p.E463G). N-glycosylation studies in plasma were normal. ICAM-1 expression was decreased in patient fibroblasts, supporting the variant's pathogenicity. Adding D-galactose to the patient's fibroblast culture increased ICAM-1 expression in vitro, offering a potential treatment option in ALG13-CDG. The present report is a new example for an N-glycosylation disorder, that may present with normal transferrin isoform analysis, and also demonstrates, that CDG type I patients can have normal cognitive development.

Tuberous Sclerosis Complex: Early Diagnosis in Infants.

Investigators from the Tuberous Sclerosis Complex (TSC) Autism Center of Excellence Research conducted two concurrent prospective longitudinal studies to analyze the timing and pattern of clinical presenting symptoms of TSC in infants to facilitate earlier diagnosis and treatment in this specific population.

Amphetamine excretion profile following multidose administration of mixed salt amphetamine preparation.

Interpretation of drug testing results requires detailed scientific information, particularly in those cases where the question of legitimate use versus illicit use arises. Amphetamine remains a widely abused drug throughout the world, although it is also used therapeutically for weight loss, narcolepsy, and attention-deficit disorder with hyperactivity (ADHD). Treatment of ADHD using stimulant drugs is much more common now than it was in even the recent past. Increasingly, older individuals are diagnosed and treated for ADHD, and treatment often continues into adulthood. Amphetamine is commonly used for the treatment of ADHD and is available by prescription as either the d-enantiomer or a mixture of enantiomers. Although used for many years, there are no data available to describe the excretion profile of amphetamine and its enantiomers following repeated use of the drug. As a result, medical review officers (MROs) and forensic toxicologists have no direct evidence to base their decisions on when it comes to evaluation of use of these drugs. The current study was designed to determine the concentration and enantiomer excretion profile following repeated daily administration of mixed enantiomers of amphetamine. Twenty milligrams of Adderall was administered daily to five healthy subjects with all subsequent ad lib urine samples collected for at least five days following administration of the five-dose regimen. Adderall is a 3:1 mixture of d- and l-enantiomers of amphetamine salts and represents the mixed enantiomer proportion of amphetamine available in the United States through pharmaceutical channels. Peak amphetamine concentrations ranged from 5739 to 19,172 ng/mL. Samples containing > or = 500 ng/mL amphetamine (the administrative cutoff for a positive result by gas chromatography-mass spectrometry) were seen up to 60:15 (h:min) following administration of the last dose. Enantiomer analysis showed the d-enantiomer to be in excess of the l-enantiomer for as long as the drug was administered. After administration of the last dose of drug, the proportion of l-enantiomer increased over time. Not all samples that contained > or = 500 ng/mL total amphetamine were positive when tested by immunoassay because of the differing cross-reactivity of the enantiomers. This study provides the first description of the excretion of amphetamine following repeated administration of Adderall. The presence of the l-enantiomer separates this drug from other formulations composed of only the d-enantiomer (i.e., Dexedrine and much illicit amphetamine), thus readily differentiating them from Adderall use. Some illicit and medicinal amphetamine is, however, a mixture of amphetamine enantiomers. Because the enantiomers are metabolized at different rates, their proportion offers the opportunity to describe excretion versus time. Coupling this data with drug concentration makes it possible for forensic toxicologists and MROs to come to an informed decision regarding the involvement of this drug in a positive drug test result.

Amphetamine enantiomer excretion profile following administration of Adderall.

Amphetamine remains a widely abused drug throughout the world. It is also used therapeutically for weight loss, narcolepsy, and attention deficit disorder with hyperactivity (ADHD). ADHD has grown dramatically recently both in terms of diagnosis and treatment. Increasingly, older individuals are diagnosed and treated for ADHD, and treatment often continues into adulthood. Of the available treatments for ADHD, Adderall is widely prescribed. Despite its widespread use, there are no published data regarding the expected amphetamine excretion profile following its use. This is problematic because, in this case, medical review officers (MRO) and forensic toxicologists are asked to assess results in terms of use pursuant to valid medical prescription without specific data on which to base a sound decision. To address this situation, a study to determine the concentration and enantiomer composition of amphetamine excretion following administration of Adderall was undertaken. Adderall (20 mg) was administered to five healthy subjects with all subsequent ad lib urine samples (total urine void) collected for seven days. Adderall is a 3:1 mixture of d- and l-enantiomers of amphetamine salts. Peak amphetamine concentrations ranged from 2645 to 5948 ng/mL. Samples containing > or = 500 ng/mL of amphetamine (the administrative cutoff for a positive result by gas chromatography-mass spectrometry) were seen up to 47:30 h post dose. The number of samples that contained amphetamine concentrations of > or = 500 ng/mL ranged among individuals from 7 to 13. As anticipated, analysis showed the d-enantiomer to be in excess of the l-enantiomer, with the proportion of l-enantiomer increasing over time. Because of the mixture of enantiomers, not all samples that contained > or = 500 ng/mL of amphetamine were positive when tested by immunoassay. The drug concentration profiles were quite variable within and between subjects because of dilution and fluctuations in pH of the samples. These results are the first to describe the excretion of amphetamine following administration of Adderall. The presence of the l-enantiomer separates this drug from other preparations of the drug that are composed of only the d-enantiomer (i.e., dexedrine and much illicit amphetamine), thus readily differentiating them from Adderall use. Some illicit and medicinal amphetamine is, however, a mixture of amphetamine enantiomers. Because the enantiomers are metabolized at different rates, their proportion offers the opportunity to describe excretion versus time. Coupling this data with drug concentration makes it possible for forensic toxicologists and MROs to come to an informed decision about the involvement of this drug in a positive drug test result. Using the combination of enantiomer composition and quantitative data will allow MROs and forensic toxicologists to better assess the use of this drug from abuse of amphetamine.

The effect of Medicare Part D on health care utilization for non-elderly Medicare recipients with disabilities.

BACKGROUND: The effect of Medicare Part D prescription drug coverage on non-elderly beneficiaries, most of whom have disabilities, has not been fully explored. OBJECTIVE: The objective of this study was to estimate the impact of Medicare Part D on expenditures and utilization of prescription drugs, hospitalizations, physician office visits and emergency department visits in non-elderly Medicare beneficiaries with disabilities. METHODS: Using Medical Expenditure Panel Survey (MEPS) data from 2005 to 2006, we assembled a cohort of non-elderly Medicare beneficiaries and controls using propensity score matching. We used zero-inflated negative binomial regressions and generalized linear models to examine the effect of Medicare Part D on health care utilization and expenditures, respectively. We controlled for demographic characteristics, census region of residence, and self-reported health status. RESULTS: We were able to match 299 Medicare non-recipients to 299 Medicare recipients. The mean (SD) age was 49.8 (10.7) years for the Medicare non-recipients and 49.9 (10.0) years for Medicare recipients. While the introduction of Medicare Part D was not associated with a significant change in the number of prescriptions consumed by this group of individuals, there was a significant decrease in out-of-pocket prescription drug expenses as well as expenses paid for by Medicaid and private insurance. CONCLUSIONS: Our study is the first to examine the impact of Medicare Part D on non-elderly Medicare beneficiaries. We find that the introduction of Medicare Part D did not lead to changes in prescription drug consumption, only in the method of payment.