A5048252135- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Mitochondrial Function and Pathology
- Biochemical and Molecular Research
- Neurogenetic and Muscular Disorders Research
- Metabolism and Genetic Disorders
- Neonatal Health and Biochemistry
- Ion Transport and Channel Regulation
- Immunodeficiency and Autoimmune Disorders
- Methemoglobinemia and Tumor Lysis Syndrome
- Neuroscience and Neuropharmacology Research
- Glycosylation and Glycoproteins Research
- Congenital Anomalies and Fetal Surgery
- Muscle metabolism and nutrition
- Hemoglobinopathies and Related Disorders
- RNA modifications and cancer
Clinic for Special Children
2018-2023
Franklin & Marshall College
2018
Over the past three decades, we studied 184 individuals with 174 different molecular variants of branched-chain α-ketoacid dehydrogenase activity, and here delineate essential clinical biochemical aspects maple syrup urine disease (MSUD) phenotype. We collected data about treatment, survival, hospitalization, metabolic control, liver transplantation from patients classic (i.e., severe; n = 176), intermediate (n 6) intermittent 2) forms MSUD. A total 13,589 amino acid profiles were used to...
Glutaric acidemia type 1 (GA1) is a disorder of cerebral organic acid metabolism resulting from biallelic mutations GCDH. Without treatment, GA1 causes striatal degeneration in >80% affected children before two years age. We analyzed clinical, biochemical, and developmental outcomes for 168 genotypically diverse patients managed at single center over 31 years, here separated into three treatment cohorts: Cohort I (n = 60; DOB 2006-2019) were identified by newborn screening (NBS) treated...
Abstract Mutations in nitrogen permease regulator-like 3 (NPRL3), a component of the GATOR1 complex within mTOR pathway, are associated with epilepsy and malformations cortical development. Little is known about effects NPRL3 loss on neuronal signalling morphology, or cerebral development seizure susceptibility. We report clinical phenotypic spectrum founder pedigree (c.349delG, p.Glu117LysFS; n = 133) among Old Order Mennonites dating to 1727. Next, as strategy define role development,...
We describe the pathophysiology, treatment, and outcome of Crigler-Najjar type 1 syndrome (CN1) in 28 UGT1A1 c.222C>A homozygotes followed for 520 aggregate patient-years.Unbound ("free") bilirubin (Bf ) was measured patient sera to characterize binding unconjugated (BT albumin (A) validate their molar concentration ratio /A) as an index neurological risk. Two custom phototherapy systems were constructed from affordable materials provide high irradiance outpatient setting; light dose...
We correlate chromosome 5 haplotypes and SMN2 copy number with disease expression in 42 Mennonite 14 Amish patients spinal muscular atrophy (SMA). A single haplotype (A1) 1 of segregated among all patients. SMN1 deletions on four different that carried (M1a, M1b, M1c) or 2 (M2) copies SMN2. DNA microsatellite microarray data revealed structural similarities A1, M1a, M2. Clinical were parsed according to both genotype (2 copies, n = 44; 3 9; 4 3). No infant sat unassisted. In contrast, 9...
Abstract Nitrogen Permease Regulator Like 3 (NPRL3) variants are associated with malformations of cortical development (MCD) and epilepsy. We report a large (n=133) founder NPRL3 (c.349delG, p.Glu117LysFS) pedigree dating to 1727, heterogeneous epilepsy MCD phenotypes. Whole exome analysis in individuals without seizures this cohort did not identify genetic modifier explain the variability seizure phenotype. Then as strategy investigate developmental effects loss human brain, we show that...
ABSTRACT Objective We created WiTNNess as a hybrid prospective/cross‐sectional observational study to simulate clinical trial for infantile‐onset TNNT1 myopathy. Our aims were identify populations future enrollment, rehearse outcome assessments, specify endpoints, and refine logistics. Methods Eligible participants had biallelic pathogenic variants of proximal weakness without confounding conditions. The primary endpoint was ventilator‐free survival. “Thriving” secondary defined the ability...