A Race Against Time-Changing the Natural History of CRIM Negative Infantile Pompe Disease.

We report the clinical course of the first prenatally diagnosed cross-reactive immunologic material (CRIM)-negative infantile Pompe disease (IPD) patient [homozygous for c.2560C>T (p.Arg854X) variant in the GAA gene] to undergo prophylactic immune tolerance induction (ITI) and enzyme replacement therapy (ERT) within the first 2 days of life. Both parents were found to be carriers of the c.2560C>T (p.Arg854X) variant through prenatal carrier screening. Fetal echocardiogram at 31 weeks of gestation showed left ventricular hypertrophy. An echocardiogram on the 1st day of life revealed marked biventricular hypertrophy. Physical exam was significant for macroglossia and hypotonia. A short course of Prophylactic ITI with rituximab, methotrexate, and intravenous immunoglobulin (IVIG) in conjunction with ERT at a dose of 20 mg/kg every other week was started on day 2 of life. The patient completed the ITI protocol safely and complete B-cell recovery, based on CD19 count, was noted by 3 months of age. The patient never developed anti-rhGAA IgG antibodies to ERT. Vaccinations were initiated at 9 months of age, with adequate response noted. Complete recovery of cardiac function and left ventricular mass was seen by 11 weeks of age. At 8 months of age, the patient developmentally measured at 75-90% on the Alberta Infant Motor Scale, walked at 11 months and continues to develop age-appropriately at 50 months of age based on the Early Learning Accomplishment Profile. ERT dosing was increased to 40 mg/kg every 2 weeks at 32 months of age and frequency increased to 40 mg/kg every week at 47 months of age. Patient continues to have undetectable antibody titers, most recently at age 50 months and urine Hex4 has remained normal. To our knowledge, this is the first report of successful early ERT and ITI in a prenatally diagnosed CRIM-negative IPD patient and the youngest IPD patient to receive ITI safely. With the addition of Pompe disease to the Recommended Uniform Screening Panel(RUSP) and its addition to multiple state newborn screening programs, our case highlights the benefits of early diagnosis and timely initiation of treatment in babies with Pompe disease, who represent the most severe end of the disease spectrum.

Cardiac mechanics in patients with human immunodeficiency virus: a study of systolic myocardial deformation in children and young adults.

Human immunodeficiency virus (HIV) infection causes dysfunction of different organ systems. Myocardial diastolic dysfunction has been reported previously in an adult HIV population. Our aim was to study myocardial strain in children and young adults infected by HIV who have apparently normal ejection fraction. Forty HIV-infected patients (mean age 20.6 ± 1.5 years) with normal ejection fraction and 55 matched normal controls (mean age 17 ± 1.5 years) were studied by two-dimensional echocardiogram. The images were stored then exported to velocity vector imaging software for analysis. Measures considered were left-ventricular peak global systolic strain (LV S) and strain rate (LV SR) as well as right-ventricular peak global systolic strain (RV S) and strain rate (RV SR). Circumferential measures of the left ventricle included the following: LV circumferential peak global systolic strain (LV circ S), strain rate (LV circ SR), radial velocity (LV rad vel), and rotational velocity (LV rot vel) at the level of the mitral valve. Statistical significance was set at p < 0.05. The means of all longitudinal deformation parameters were significantly lower in HIV patients compared with normal controls: LV S (-14.15 vs. -19.31), LV SR (-0.88 vs. -1.30), RV S (-19.58 vs. -25.09), and RV SR (-1.34 vs. -2.13), respectively (p < 0.05). LV rot vel was lower in patients compared with controls (43.23 vs. 51.71, p = 0.025). LV circ S, LV circ SR, and LV rad vel showed no significant difference between the two groups (p ≥ 0.05). HIV infection affects longitudinal systolic cardiac strain and strain rate in children and young adults. Normal ejection fraction might be attributed to preserved circumferential myocardial deformation. Strain and strain rate may help identify HIV patients at high risk for cardiac dysfunction and allow early detection of silent myocardial depression.

Point-of-care testing for B-type natriuretic peptide in premature neonates with patent ductus arteriosus.

Patent ductus arteriosus (PDA) is highly prevalent in pre-term neonates (PTN) and has been recognized as a neonatal co-morbidity. The purpose of this study was to determine if levels of brain (or B-type) natriuretic peptide (BNP), a peptide secreted by ventricular myocytes in response to volume or pressure overload, correlate with the size of the PDA. In a prospective design, 52 PTN (no PDA: n=24; PDA: n=28) were studied after obtaining parental consent. Those with genetic anomalies and congenital heart disease, except for PDA and patent foramen ovale, were excluded. Echocardiographic estimates of the diameters of the PDA (or absence of PDA) were made concurrently with capillary blood collection for BNP assay. BNP levels in samples from PTN without PDA were 23.6 ng/L (median); 13.1 to 32.3 ng/L (IQR); initial samples (between days 3 and 7 of life) with small PDA (n=11), median 66.1 ng/L; 55.5 to 85.3 ng/L (IQR); with moderate PDA (n=6) median 284 ng/L; 204 to 622 ng/L (IQR); and with large PDA (n=11) 2410 ng/L median; 420 to 2770 ng/L (IQR). (p< 0.0001 for ANOVA; groupwise: p<0.05 for both no PDA vs. moderate and large PDA); Trend analysis suggested a strong association of BNP with size of PDA (p<0.001). Of 17 subjects with moderate to large PDA, pre and post-treatment (Ibuprofen; per standard protocol) data were obtained on 12 subjects. Pre-treatment BNP ranged from 111 to 5000 ng/L; post-treatment BNP decreased to 5.0 to 262 ng/L (p = 0.0005). Estimates of decision levels for treatment were made by examining dichotomized groups, i.e., no-to-small vs. moderate-to-large and using receiver-operator characteristic (ROC) curve analysis yielding a value of 123 ng/L. BNP may obviate repeated echocardiography as follow up after treatment, or to monitor future course of respiratory distress secondary to PDA in PTN.

Varicella myopericarditis mimicking myocardial infarction in a 17-year-old boy.

Varicella (chickenpox), a common childhood infection caused by the varicella-zoster virus, is self-limiting and usually benign. Although atypical manifestations of the virus are occasionally seen, it rarely presents with cardiovascular sequelae. Cardiovascular complications of varicella can include pericarditis, myocarditis, or endocarditis. Herein, we report the case of a 17-year-old boy who had varicella infection and severe chest pain. Examination revealed atypical electrocardiographic findings of pericarditis and remarkably elevated cardiac biomarker levels: peak cardiac troponin I, 37.2 ng/mL; total creatine kinase, 1,209 U/L; and creatine kinase-MB fraction, 133.6 ng/mL. After results of coronary angiography reliably excluded ischemia and myocardial infarction, the diagnosis was varicella myopericarditis. The patient was placed on a medical regimen during and after 5 days of hospitalization. In 2 weeks, he was asymptomatic, and at 6 months, he was doing well and had normal electrocardiographic and echocardiographic results.To our knowledge, cardiac enzyme elevations to these levels have not been reported in cases of cardiovascular sequelae of varicella. We discuss the diagnostic challenges of this atypical case and suggest that clinicians be aware that varicella disease is most often, but not always, benign.