Novel mutations in two unrelated Italian patients with SSADH deficiency.

Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a rare autosomal recessive disorder of γ-aminobutyric acid (GABA) catabolism caused by mutations in the gene coding for succinic semialdehyde dehydrogenase (ALDH5A1). The abnormal levels of GHB detected in the brain and in all physiological fluids of SSADHD patients represent a diagnostic biochemical hallmark of the disease. Here we report on the clinical and molecular characterization of two unrelated Italian patients and the identification of two novel mutations: a 22 bp DNA duplication in exon 1, c.114_135dup, p.(C46AfsX97), and a non-sense mutation in exon 10, c.1429C > T, p.(Q477X). The two patients showed very different clinical phenotypes, coherent with their age. These findings enrich the characterization of SSADHD families and contribute to the knowledge on the progression of the disease.

Significant QT interval prolongation and long QT in young adult ex-preterm newborns with extremely low birth weight.

BACKGROUND: The survival rate for extremely low birth weight (ELBW) infants born preterm is on an increasing upward trend, despite the possibility of neuro-cerebral consequences in later life. To date, scarce information is available on the effect of extreme prematurity on cardiovascular system. AIM: To verify the presence of standard echocardiographic and ECG alterations in ex-ELBW young healthy adults. METHOD: A color Doppler echocardiogram and an ECG were performed on 24 ex-ELBW (4 males and 20 females; mean: 23.2 ± 3.3 years), compared with 24 healthy subjects born at term (C). ECG parameters examined: PR, QT, QT(c), and QT dispersion (QT(d)). Gestational age, birth weight, and duration of stay in neonatal intensive care unit were obtained from clinical records. RESULTS: Transthoracic echocardiography did not reveal differences between ex-ELBW and C, while a significant difference was displayed by ex-ELBW with regard to PR (141.5 ± 13.4 ms vs. 164.2 ± 24.0 ms, p < 0.0003), QT(c) (417.0 ± 23.6 ms vs. 369.9 ± 19.5 ms, p =0.00001), and QT(d) (30.4 ± 14.1 ms vs. 24.6 ± 8.2 ms, p < 0.00001). In two patients (8.3%), QT(c) exceeded the upper limit of normal range. A statistically significant inverse correlation was observed between QT(c) and gestational age (r = -0.67, p < 0.0003). CONCLUSIONS: QT(c) and QT(d) in ex-ELBW were found to be at the upper limit of normal range and correlated with gestational age and birth weight; in two cases, QT(c) exceeded the upper limit. This study, irrespective of the pathophysiological mechanism involved, underlines a potential risk for ex-ELBW of developing ventricular arrhythmias when using drugs capable of prolonging QT interval. SUMMARY: QT(c) and QT(d) in young adults previously born preterm with an ELBW (401-1000 g) were generally found to be at the upper limit of normal range and correlated with gestational age and birth weight. This finding underlines a potential risk for ex-ELBW of developing ventricular arrhythmias when using drugs capable of prolonging QT interval.