Muscle eye brain disease – phenotype of glycosylation deficiency?

Diagnosis of muscle eye brain disease is based on clinical symptoms and grouped in congenital muscular dystrophies because of the myopathy. Recent researches showed in some patients a mutant glycosyltransferase located in the PomGnT1 gene and allowed classifying to the family of glycosylation deficiency.

Case report: Second child, related parents. Two miscarriages in 18th and 22nd week of pregnancy, unknown reason. Ultrasound while pregnancy showed a hydrocephalus. After delivery multiple intracerebral malformations seen in ultrasound.

Intracerebral malformation: hydrocephalus with stenosis of aquaeduct. Dandy walker malformation

(hypoplasia of the vermis and cerebellar hemisphere), absent septum pellucidum. Eye malformation:

persistent hypoplastic vitrious ball. Muscle: elevated CPK and muscular hypotonia. Muscle biopsy with a normal result. Typical mutation for MEBD.

Discussion: Because of variant phenotyps in MEB disease we recommend expand diagnostic research in eyes and muscle. Complications are VP-shunt dependent hydrocephalus, epilepsy and feeding problems. Till now, we attached the MEB disease to the group of congenital muscular dystrophies as a variant group with weakness and muscular atrophy or dystrophy. Glycosylation deficiency is classified in N-and O-glycosylation. A defect in PomGnT1 gene, found in MEB disease, is responsible for an impaired O-glycosylation, finally being involved in an incorrect migration of neuronal cells during embryogenesis. It is also responsible for binding activity of muscular cells. Altered glycosylation may play a critical role in the pathomechanism of MEB disease. Screening for defects in O-glycosylation is isoelectric focussing of APO CIII.