A family with autosomal dominant Glut-1 deficiency syndrome (DS) affecting 5 members over 3 generations is reported from the University of Goettingen, Germany; and Columbia University, New York. Clinical and laboratory features of 2 brothers and a mother showed severe to mild seizures (nodding, eye rolling, jerking, and atonia, with loss of consciousness), delayed motor and mental development, severe to mild ataxia-dystonia or clumsiness, hypoglycorrhachia (<40 mg/dl; reduced CSF/blood glucose ratio (0.33, normal, 0.65)), and decreased erythrocyte 3-O-methyl-D- glucose uptake. Deceleration in head growth in early childhood was associated with greater neurological impairment in one brother. Fasting accelerated, whereas feeding carbohydrate delayed, neurological deterioration. Antiepileptic drugs were ineffective, and phenobarbital worsened infantile seizures (phenobarbital inhibits Glut-1 facilitated transport of glucose and dehydroascorbic acid). The ketogenic diet controlled seizures. A heterozygous R126H missense mutation was identified in the 3 patients tested. [1]

COMMENT. This is the first report of a familial multigenerational case of Glut-1 deficiency syndrome. De Vivo et al (1991) first described Glut-1 DS in 2 children and subsequently reported 20 patients with various mutations. Symptoms present in the first year, with delayed motor and mental development, worsened by fasting, seizures refractory to antiepileptic drugs (AED) and aggravated by phenobarbital, and hypoglycorrhachia. A spinal tap and CSF glucose determination are important in a diagnostic workup of infants and young children with AED-resistant seizures, developmental delay, and ataxia. A decreased erythrocyte 3-OMG uptake and demonstration of heterozygous GLUT-1 mutations confirm the diagnosis. Barbiturates and methylxanthines, found to aggravate the seizures, should be avoided, and the ketogenic diet is used in treatment, at least in early childhood. Patients may continue to suffer from episodic limpness, ataxia, and confusion.