LETTER TO THE EDITOR - Unexplained epileptic encephalopathy: consider and reconsider pyridoxine dependent seizures

To The Editor: The following case history illustrates the diagnostic pitfalls of pyridoxine dependent epilepsy that may lead to serious delay in treatment. A 5 months old boy was referred to our hospital because of a diffuse encephalopathy with multifocal epilepsy, severe developmental delay and a bipyramidal syndrome. The pregnancy and delivery were uncomplicated. One hour after birth the first seizures were noted with multifocal epileptic activity on the electroencephalogram (EEG). The epileptic activity did not diminish after the intravenous administration of 100 mg pyridoxine shortly after the debut of seizures, and after 300 mg ten days later. Early diagnostic evaluation revealed no infections, nor endocrine or metabolic disturbances. Magnetic resonance imaging (MRI) of the brain was normal. The metabolic analysis included measurement of gama-aminobutyric acid (GABA) and amino acids in cerebrospinal fluid. The child was treated with vigabatrine and phenobarbital successively without satisfactory seizure control

Identification of three patients with a very mild form of Smith-Lemli-Opitz syndrome

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive malformation syndrome characterized by mental retardation, congenital anomalies, and growth deficiency. The syndrome is caused by a block in cholesterol biosynthesis at the level of 7-dehydrocholesterol reductase (7-DHCR), which results in elevated levels of the cholesterol precursor 7-dehydrocholesterol (7-DHC) and its isomer 8-dehydrocholesterol (8-DHC). We report on three patients from two families with a very mild clinical presentation of SLOS. Their plasma cholesterol values were normal and their plasma levels of 7- and 8- DHC were only slightly elevated. In cultured skin fibroblasts, a significant residual 7-DHCR activity was found. All three patients were compound heterozygotes for a novel mutation affecting translation initiation (M1L). Two of them had the common IVS8-1G>C null mutation and the third patient an E448K mutation in the 7-DHCR gene. Our findings emphasize the importance of using a sensitive method for measuring precursors of cholesterol in combination with mutation analysis to analyze patients with only minimal clinical SLOS-like sign