ALG6-CDG in South Africa: Genotype-Phenotype Description of Five Novel Patients.

ALG6-CDG (formerly named CDG-Ic) (phenotype OMIM 603147, genotype OMIM 604566), is caused by defective endoplasmic reticulum α-1,3-glucosyltransferase (E.C 2.4.1.267) in the N-glycan assembly pathway (Grünewald et al. 2000). It is the second most frequent N-glycosylation disorder after PMM2-CDG; some 37 patients have been reported with 21 different ALG6 gene mutations (Haeuptle & Hennet 2009; Al-Owain 2010). We report on the clinical and biochemical findings of five novel Caucasian South African patients. The first patient had a severe neuro-gastrointestinal presentation. He was compound heterozygous for the known c.998C>T (p.A333V) mutation and the novel c.1338dupA (p.V447SfsX44) mutation. Four more patients, presenting with classical neurological involvement were identified and were compound heterozygous for the known c.257 + 5G>A splice mutation and the c.680G>A (p.G227E) missense mutation. The patients belong to a semi-isolated Caucasian community that may have originated from European pioneers who colonized South Africa in the seventeenth/eighteenth centuries.

Trans-cranial placement of an amplatzer device to control intractable cardiac failure in an infant with a vein of galen anomaly. A case report.

Neonates presenting with intractable cardiac failure due to vein of Galen aneurysmal malformations (VGAMs) rapidly progress to multisystem organ failure and death if left untreated. Currently the only viable treatment option is endovascular embolization. Although intracranial embolization of a neonate is a high-risk procedure, successful treatment can reverse cardiac failure and prevent neurological complications associated with VGAMs. Embolization via the arterial route is thought to have a better outcome than embolization via the venous system. However, multiple transarterial embolizations in different sessions may well be contraindicated in neonates, because repeat access via the femoral artery, carries a risk of arterial trauma which, in turn, can jeopardize lower limbs. With this case study we show that after repeat failure of arterial embolization, the transcranial placement of an Amplatzer PFO occluder (AGA Medical, Plymouth, USA) in the aneurysm can effectively reduce intrafistular pressure and venous outflow velocity. We also propose a mathematical model that can be used to calculate flow velocity through the aneurysm, which, in turn, could be used to aid clinical decision-making. Unlike some conventional techniques, the placement of an Amplatzer occluder does not pose the risk of completely obstructing venous drainage and therefore does not increase the risk of venous breakthrough hemorrhage. We propose this endovascular technique as a treatment option for high risk neonates in need of emergency embolization of VGAMs, where multiple arterial embolizations failed to control the condition sufficiently.

Distal truncation of KCC3 in non-French Canadian HMSN/ACC families.

BACKGROUND: Hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC) is a severe and progressive autosomal recessive polyneuropathy. Mutations in the potassium-chloride cotransporter 3 gene (KCC3) were identified as responsible for HMSN/ACC in the French Canadian (FC) population. In the present study, the authors were interested in finding new mutations in non-FC populations, assessing the activity of mutant proteins and refining genotype-phenotype correlations. METHODS: The authors screened KCC3 for mutations using direct sequencing in six non-FC HMSN/ACC families. They then assessed the functionality of the most common mutant protein using a flux assay in Xenopus laevis oocytes. RESULTS: The authors identified mutations in exon 22 of KCC3: a novel mutation (del + 2994-3003; E1015X) in one family, as well as a known mutation (3031C-->T; R1011X) found in five unrelated families and associated with two different haplotypes. The function of the cotransporter was abolished, although a limited amount of mutant proteins were correctly localized at the membrane. CONCLUSIONS: KCC3 mutations in exon 22 constitute a recurrent mutation site for hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC), regardless of ethnic origin, and are the most common cause of HMSN/ACC in the non-French Canadian (FC) families analyzed so far. Therefore, for genetic analysis, exon 22 screening should be prioritized in non-FC populations. Finally, the R1011X mutation leads to the abrogation of KCC3's function in Xenopus laevis oocytes, likely due to impaired transit of the cotransporter.

Pyloric stenosis presenting as severe prolonged jaundice. A case report.

A 17-day-old infant with pyloric stenosis presenting with severe neonatal jaundice is described. The bilirubin level rose to 371 mumol/l and an exchange transfusion was considered. No history of frequent or forceful vomiting was given and the usual symptoms and signs of pyloric stenosis were absent. Radiographic studies revealed features typical of hypertrophic pyloric stenosis. At laparotomy a pyloromyotomy was performed and the jaundice subsided rapidly.