Delayed diagnosis and racial bias in children with genetic conditions.

As more therapeutics for genetic conditions become available, the need for timely and equitable genetic diagnosis has become urgent. Using clinical cases, we consider the health system-, provider-, and patient-level factors that contribute to the delayed diagnosis of genetic conditions in pediatric patients from minority populations, leading to health disparities between racial groups. We then provide suggestions to address these factors, with the aim of improving minority health and access to genetic care for all children.

Inpatient cost analysis for treatment of myasthenia gravis.

INTRODUCTION: We explore trends in U.S. inpatient costs of care over a 10-year period. METHODS: We compare myasthenia gravis (MG) with multiple sclerosis (MS) and overall U.S. hospital admissions using the Agency for Healthcare Research and Quality Nationwide Inpatient Sample database for 2003-2013. RESULTS: Total costs of MG inpatient care rose 13-fold from 2003 to 2013. This was accounted for by a greater than sixfold increase in discharges and a greater than twofold increase in cost per discharge. The < 17 and >85 years age groups experienced the greatest increases in discharges. Medicare and Medicaid use increased. Regional variations in cost were apparent. There were greater rises in the Midwestern and Southern United States, which is dissimilar to MS and all hospital admissions. DISCUSSION: There was a dramatic and disproportionate rise in the number of MG discharges, most likely because of changes in practice patterns. Muscle Nerve 56: 1114-1118, 2017.

Vitelline vascular remnant causing intestinal obstruction in a patient with TARP syndrome.

BACKGROUND: TARP syndrome, characterized by talipes equinovarus, atrial septal defect, Robin sequence, and persistent left superior vena cava, is an X-linked recessive condition caused by deleterious variants in RBM10. Vitelline vascular remnants (VVR) are a rare vitelline duct anomaly with approximately 26 cases previously reported. There are no previously reported cases of VVRs in patients with TARP syndrome. CASE: We present a male neonate diagnosed with TARP syndrome via trio whole exome sequencing who had classic features of this syndrome, although his course was additionally complicated by feeding intolerance with multiple episodes of abdominal distension. Serial imaging and contrast studies of the upper GI tract and small bowel demonstrated small bowel obstruction of unclear etiology. Given the poor prognosis associated with this condition, life-sustaining measures were withdrawn, and he passed away at 38 days of age. On autopsy, a VVR was unexpectedly identified with proximal bowel dilation, explaining his feeding intolerance. CONCLUSIONS: We highlight the importance of full post-mortem examination in understanding the complete spectrum of manifestations of genetic syndromes and provide a review of the literature.

Lysinuric protein intolerance: Pearls to detect this otherwise easily missed diagnosis.

BACKGROUND: Lysinuric protein intolerance (LPI) is a rare autosomal recessive disorder characterized by deficient membrane transport of cationic amino acids. It is caused by pathogenic variants in SLC7A7, resulting in impairment of intestinal import and renal proximal tubule loss of the affected amino acids. LPI typically presents with gastrointestinal symptoms, such as vomiting, diarrhea, and failure to thrive. CASE REPORT: A 4-year-old African-American boy presented with multiple respiratory tract infections, weight loss in the setting of chronic diarrhea and worsening abdominal distention, and multiple episodes of rectal prolapse. Development was unaffected. Laboratory examination demonstrated mild anemia, hypokalemia and hypoalbuminemia, transaminitis, and normal ammonia. Initial urine amino acid analysis did not show major elevations of lysine and ornithine, often lower than expected in the setting of malnutrition. Upon initiation of total parenteral nutrition (TPN), his urine amino acids showed a characteristic profile of dibasic aminoaciduria. CONCLUSIONS: Failure to thrive, chronic diarrhea, and hepatomegaly should raise suspicion for LPI. Urine amino acids can be normal in this condition in the setting of malnutrition, a common complication of the disease. Additionally, it has been previously shown that the plasma arginine and ornithine concentration is higher in LPI subjects.

Shortage of generic neurologic therapeutics: An escalating threat to patient care.

OBJECTIVE: To assess longitudinal trends in shortages of generic drugs used for neurologic conditions over a 15-year period in the United States. METHODS: Drug shortage data from the University of Utah Drug Information Service (UUDIS) from 2001 to 2015 were analyzed. Medications were included that were likely to be prescribed by a neurologist to treat a primary neurologic condition or critical for care of a patient with a neurologic condition. Trends in shortage length were assessed using standard descriptive statistics. RESULTS: A total of 2,081 shortages were reported by UUDIS and 311 (15%) involved medications for neurologic conditions. After excluding discontinued products, 291 shortages were analyzed. The median number of neurologic drugs in shortage was 21 per month with a median duration of 7.4 months. During the three 5-year periods of 2001-2005, 2006-2010, and 2011-2015, a median of 12.5, 14, and 45 drugs were in shortage, respectively. A maximum of 50 drugs in shortage was reached in December 2012 and December 2014. By the end of the study period, 30 neurologic drugs remained in shortage. In over half of the shortages, manufacturers did not provide a reason for the shortage. When reported, manufacturing delays, followed by supply/demand issues, raw material shortages, regulatory issues, and business decisions were cited. CONCLUSIONS: Continued drug shortages may compromise the care of patients with neurologic conditions. Manufacturers, together with professional organizations, patient advocacy groups, and the government, need to continue to address this issue, which may escalate with a growing burden of neurologic disease.