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Biomedical subjects

Lambertus Dorland

Publications and source records attributed to Lambertus Dorland.

2 recordsLinked to original sources

D-serine in the developing human central nervous system.

To elucidate the role of D-serine in human central nervous system, we analyzed D-serine, L-serine, and glycine concentrations in cerebrospinal fluid of healthy children and children with a defective L-serine biosynthesis (3-phosphoglycerate dehydrogenase deficiency). Healthy children showed high D-serine concentrations immediately after birth, both absolutely and relative to glycine and L-serine, declining to low values at infancy. D-Serine concentrations were almost undetectable in untreated 3-phosphoglycerate dehydrogenase-deficient patients. In one patient treated prenatally, D-serine concentration was nearly normal at birth and the clinical phenotype was normal. These observations suggest a pivotal role for D-serine in normal and aberrant human brain development.

Central Nervous System↗

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 signs.

Adolescent↗