A metabolic signature for NADSYN1-dependent congenital NAD deficiency disorder.

Nicotinamide adenine dinucleotide (NAD) is essential for embryonic development. To date, biallelic loss-of-function variants in 3 genes encoding nonredundant enzymes of the NAD de novo synthesis pathway - KYNU, HAAO, and NADSYN1 - have been identified in humans with congenital malformations defined as congenital NAD deficiency disorder (CNDD). Here, we identified 13 further individuals with biallelic NADSYN1 variants predicted to be damaging, and phenotypes ranging from multiple severe malformations to the complete absence of malformation.

Novel Case of Prader-Willi Syndrome and Ebstein's Anomaly: Implications for Complex Care Management.

We present a patient with a complex phenotype including diagnoses of Ebstein's anomaly and Prader-Willi syndrome (PWS) as well as additional congenital anomalies and genetic variants with potential clinical effects. This is the first reported case of both diagnoses present in the same patient. The diagnosis of Ebstein's anomaly was made on prenatal ultrasound.

Newborn screening for Pompe disease: Parental experiences and follow-up care for a late-onset diagnosis.

Newborn screening (NBS) for Pompe disease (PD) was added to the Recommended Uniform Screening Panel (RUSP) in the United States in 2015 because there was compelling evidence of health benefits for early diagnosis of Infantile-onset Pompe disease (IOPD). However, one limitation of NBS for PD is its inability to distinguish IOPD and late onset forms of Pompe disease (LOPD). Management of LOPD is challenging because of uncertainty around progression of LOPD and determining the appropriate time for treatment initiation.

Exploiting pre-rRNA processing in Diamond Blackfan anemia gene discovery and diagnosis.

Diamond Blackfan anemia (DBA), a syndrome primarily characterized by anemia and physical abnormalities, is one among a group of related inherited bone marrow failure syndromes (IBMFS) which share overlapping clinical features. Heterozygous mutations or single-copy deletions have been identified in 12 ribosomal protein genes in approximately 60% of DBA cases, with the genetic etiology unexplained in most remaining patients. Unlike many IBMFS, for which functional screening assays complement clinical and genetic findings, suspected DBA in the absence of typical alterations of the known genes must frequently be diagnosed after exclusion of other IBMFS.