Congenital disorder of glycosylation type Ia: heterogeneity in the clinical presentation from multivisceral failure to hyperinsulinaemic hypoglycaemia as leading symptoms in three infants with phosphomannomutase deficiency.

We describe three patients with congenital disorder of glycosylation (CDG) type Ia, all of whom had persistent hyperinsulinaemic hypoglycaemia responding to diazoxide therapy as a common feature. The first patient, an infant girl, presented with recurrent vomiting, failure to thrive, liver impairment, hypothyroidism and a pericardial effusion. The second patient, also female, had a milder disease with single organ involvement, presenting as isolated hyperinsulinaemic hypoglycaemia, not associated with any cognitive impairment. The third patient, a boy presented with multi-organ manifestations including congenital hypothyroidism, persistent hyperinsulinaemic hypoglycaemia, coagulopathy, olivopontocerebellar hypoplasia and recurrent pancreatitis. All three patients had a type 1 serum transferrin isoform pattern, and were subsequently found to have low phosphomannomutase activity, confirming the diagnosis of CDG type Ia. Our findings emphasize that CDG should be considered as a differential diagnosis in patients with persistent hyperinsulinaemic hypoglycaemia and that it may even occasionally be the leading symptom in CDG Ia.

Myocyte-specific enhancer binding factor 2C expression in gerbil brain following global cerebral ischemia.

Myocyte-specific enhancer binding factor 2 (MEF2C) is a transcription factor expressed at high levels in brain. In this study, the distribution of MEF2C expression in brain was studied in normal adult gerbils and in adult gerbils subjected to 10 min of global cerebral ischemia. In normal animals, MEF2C-immunoreactivity and messenger RNA expression were detected in cortex, hippocampus, caudate-putamen, thalamus, hypothalamus, and amygdala. Within the hippocampus, MEF2C-immunoreactivity and MEF2C messenger RNA were found in interneurons scattered through the CA fields, a subset of which are parvalbumin-immunoreactive. MEF2C-immunoreactivity and MEF2C messenger RNA were also present in granule cells in the dentate gyrus. MEF2C-immunoreactivity was also detected in microglia in the hippocampus. After transient forebrain ischemia, CA1 pyramidal neurons, which are MEF2C-negative, degenerate whereas MEF2C-positive interneurons survive. Our results thus indicate that MEF2C is a marker for hippocampal neurons that are resistant to ischemia. It remains to be determined whether MEF2C plays a direct role in protecting the neurons that express it from ischemic injury. In addition, MEF2C-immunoreactivity is present in microglia, and, after ischemia, there were increased numbers of MEF2C-immunoreactive microglia in CA1, so MEF2C-immunoreactivity is a marker of both resting and activated microglia.