Extremely high mutation load of the mitochondrial 8993 T>G mutation in a newborn: implications for prognosis and family planning decisions.

Unlabelled: The propositus presented with hypotonia, respiratory failure, and seizures in the newborn period and was found to have severe hyperlactacidemia and a hypertrophic heart. He carried a de novo pathogenic mutation (m.8993 T>G) in the gene encoding subunit 6 of the mitochondrial ATP synthase (MTATP6).

Lactic acidosis in a newborn with adrenal calcifications.

A patient is reported who presented in the newborn period with an unusual combination of congenital lactic acidosis and bilateral calcifications in the adrenal medulla, visible on standard abdominal x-ray and ultrasound examination. At birth, the proband was hypotonic and dystrophic. She developed respiratory insufficiency, cardiomegaly, and hepatomegaly and died at the age of 38 d.

Clinical and molecular phenotype of Aicardi-Goutieres syndrome.

Aicardi-Goutieres syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3'-->5' exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease complex. To define the molecular spectrum of AGS, we performed mutation screening in patients, from 127 pedigrees, with a clinical diagnosis of the disease.

Congenital pontocerebellar atrophy and telencephalic defects in three siblings: a new subtype.

We report three siblings, two of whom had a neuropathological study, with a new subtype of congenital ponto-cerebellar atrophy (PCH). In addition to the brain stem and cerebellar anomalies common to all types of this heterogeneous condition, there were unique developmental defects in the telencephalon: absence of the claustrum, diffuse cortical changes particularly in the insula and an extremely small brain. In an attempt to shed some light on the pathogenesis of this developmental disorder, we have analyzed the pattern of brain stem and cerebellar abnormalities in ours and in previously reported patients with PCH, to possibly distinguish primary from secondary effects of the mutant gene upon the cerebellar circuitry, and compared our patients' cerebellar and cerebral defects to those of some other human brain malformations and to mutant mice with both hindbrain and forebrain anomalies.

Unilateral bloody nipple discharge in a two-month-old male.

Bloody nipple discharge is a rare but distressing finding in neonates and infants. We report on a 2-month-old boy with unilateral bloody nipple discharge. Ultrasound examination revealed dilated mammary ducts.

Phototherapy-mediated syndrome of inappropriate secretion of antidiuretic hormone in an in utero selective serotonin reuptake inhibitor-exposed newborn infant.

Although selective serotonin reuptake inhibitors (SSRIs) have gained wide acceptance in the off-label treatment of mental disorders in pregnant women, there seems to be an increased risk for serotonergic adverse effects in newborn infants who are exposed to SSRIs during late pregnancy. Hyponatremia as a result of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a relatively common serious side effect of the use of SSRIs in (mostly elderly) adults. Severe hyponatremia as a result of an SIADH is proposed here as part of a neonatal serotonin toxicity syndrome in a newborn infant who was exposed prenatally to an SSRI.

Transplacental passage of a nonionic contrast agent.

Unlabelled: We report the presence of iopromide in the bowel and urine of a preterm infant, born 10 days after intravenous administration of the nonionic monomer to his mother. Excessive urinary iodine excretion and borderline hyperthyrotropinaemia were observed in the infant. Moreover, crossing of the fetal blood-brain barrier was demonstrated by detection of the angiographic material in CSF and thus direct fetal neurotoxic effects cannot be excluded.

Processing of N-linked carbohydrate chains in a patient with glucosidase I deficiency (CDG type IIb).

Recently, we reported a novel congenital disorder of glycosylation (CDG-IIb) caused by severe deficiency of the glucosidase I. The enzyme cleaves the alpha1,2-glucose residue from the asparagine-linked Glc(3)-Man(9)-GlcNAc(2) precursor, which is crucial for oligosaccharide maturation. The patient suffering from this disease was compound-heterozygous for two mutations in the glucosidase I gene, a T-->C transition in the paternal allele and a G-->C transition in the maternal allele.