An incidental finding in newborn screening leading to the diagnosis of a patient with ECHS1 mutations.

Short-chain enoyl-CoA hydratase (ECHS1) is a mitochondrial beta-oxidation enzyme involved in the metabolism of acyl-CoA fatty acid esters, as well as in valine metabolism. ECHS1 deficiency has multiple manifestations, including Leigh syndrome early at birth or in childhood with poor prognosis, to cutis laxa, exercise-induced dystonia and congenital lactic acidosis. Here we describe the case of a newborn with mutations in ECHS1 that caught our attention after the incidental finding of 3-hydroxy-butyryl\3-hydroxy-isobutyryl\malonylcarnitine (C4OH\C3DC) and tiglylcarnitine (C5:1) on blood spot in the newborn screening (NBS) program. Diagnosis was suspected based on the analysis of organic acids on dried urine spot. A moderate increase of 2-methyl-2,3-dihydroxybutyric acid, was detected, which is a known marker of this disease. Exome analysis showed c.404A>G (p.Asn135Ser) mutation in homozygosis in the ECHS1 gene. The child was therefore admitted to the hospital. Initial examination showed little response to auditory stimuli and mild hypertonia of the extremities. Clinical deterioration was evident at 4 months of age, including neurological and cardiac involvement, and the patient died at 5 months of age. This case illustrates how an incidental detection in the NBS Program can lead to the diagnosis ECHS1 deficiency. Although it is a severe disease, with no treatment available, early detection would allow adequate genetic counseling avoiding the odyssey that suffered most of these families.

The Influence of Nitrile Gloves on the Setting Behavior of Polyvinyl Siloxane Putty Impression Materials.

OBJECTIVE: The purpose of this study was to assess the gelation and polymerization time of three polyvinyl siloxane (PVS) putty materials and to determine if those times were affected by nitrile gloves under different conditions. MATERIALS AND METHODS: Ten specimens (n=10) were obtained for each PVS putty material (Express STD, 3M ESPE; Extrude Xtra, Kerr and Exafast, GC) and tested under different conditions (gloves washed, gloves unwashed and hands contaminated). The gelation and polymerization time were measured using an oscillating rheometer and recorded for 400 s at 37°C to simulate the oral environment. RESULTS: The mean gelation time of hand contaminated specimens was 157.50 minutes and was significantly slower than that by using nitrile washed gloves (mean=117.94, p=.004) and by using unwashed gloves (mean=99.46, p⟨0.001). Unwashed gloves had significantly quicker gelation times compared to washed gloves (p=.046). The gelation time was significantly delayed with Exafast compared to Extrude Xtra and Express STD across all the different types of glove conditions (p⟨0.043). No significant differences were observed between polymerization time with Exafast and Extrude Xtra Putty. CONCLUSIONS: Extrude Xtra putty material had significantly better performance than GC Exafast and Express. Hand contaminated specimens were affected by the gelation/polymerization time.

Molecular testing of 163 patients with Morquio A (Mucopolysaccharidosis IVA) identifies 39 novel GALNS mutations.

Morquio A (Mucopolysaccharidosis IVA; MPS IVA) is an autosomal recessive lysosomal storage disorder caused by partial or total deficiency of the enzyme galactosamine-6-sulfate sulfatase (GALNS; also known as N-acetylgalactosamine-6-sulfate sulfatase) encoded by the GALNS gene. Patients who inherit two mutated GALNS gene alleles have a decreased ability to degrade the glycosaminoglycans (GAGs) keratan sulfate and chondroitin 6-sulfate, thereby causing GAG accumulation within lysosomes and consequently pleiotropic disease. GALNS mutations occur throughout the gene and many mutations are identified only in single patients or families, causing difficulties both in mutation detection and interpretation. In this study, molecular analysis of 163 patients with Morquio A identified 99 unique mutations in the GALNS gene believed to negatively impact GALNS protein function, of which 39 are previously unpublished, together with 26 single-nucleotide polymorphisms. Recommendations for the molecular testing of patients, clear reporting of sequence findings, and interpretation of sequencing data are provided.