Carbohydrate-deficient glycoprotein syndrome type 1 (CDG1 or Jaeken syndrome) is the prototype of a class of genetic multisystem disorders characterized by defective glycosylation of glycoconjugates. It is mostly a severe disorder which presents neonatally. There is a severe encephalopathy with axial hypotonia, abnormal eye movements and pronounced psychomotor retardation, as well as a peripheral neuropathy, cerebellar hypoplasia and retinitis pigmentosa. The patients show a peculiar distribution of subcutaneous fat, nipple retraction and hypogonadism. There is a 20% lethality in the first years of life due to severe infections, liver insufficiency or cardiomyopathy. CDG1 shows an autosomal recessive mode of inheritance and has been mapped to chromosome 16p. Most patients show a deficiency of phosphomannomutase (PMM)8, an enzyme necessary for the synthesis of GDP-mannose. We have cloned the PMM1 gene, which is on chromosome 22q13 (ref.9). We now report the identification of a second human PMM gene, PMM2, which is located on 16p13 and which encodes a protein with 66% identity to PMM1. We found eleven different missense mutations in PMM2 in 16 CDG1 patients from different geographical origins and with a documented phosphomannomutase deficiency. Our results give conclusive support to the biochemical finding that the phosphomannomutase deficiency is the basis for CDG1.

The conserved oligomeric Golgi (COG) complex is a heterooctameric complex that regulates intraGolgi trafficking and the integrity of the Golgi compartment in eukaryotic cells. Here, we describe a patient with a mild form of congenital disorder of glycosylation type II (

Serine concentrations were markedly decreased in the cerebrospinal fluid of two brothers with congenital microcephaly, profound psychomotor retardation, hypertonia, epilepsy, growth retardation, and hypogonadism. The youngest boy also had congenital bilateral cataract. Magnetic resonance imaging of the brain showed evidence of dysmyelination. Plasma serine as well as plasma and cerebrospinal fluid glycine concentrations were also decreased but to a lesser extent. Treatment with oral serine in the youngest patient significantly increased cerebrospinal fluid serine and abolished the convulsions. In fibroblasts of both patients, a decreased activity was demonstrated of 3-phosphoglycerate dehydrogenase, the first step of serine biosynthesis ( 22% and 13% of the mean control value). This is an unusual disorder as the great majority of aminoacidopathies are catabolic defects. It is a severe but potentially treatable inborn error of metabolism that has not been previously reported in man.(Arch Dis Child 1996;74:542-545 Case reports The patients, two brothers, were from a Turkish family. The parents were first cousins. They were healthy and had a normal height and head circumference.Their first child was healthy and showed normal plasma amino acid concentrations. The third child (case 1) was born after a normal term pregnancy with weight of 2130 g (3rd centile 2600 g), length 43 cm (3rd centile 47 cm), and head circumference 29 cm (3rd centile 33 cm). At the age of 3.5 months he was admitted for investigation of congenital bilateral cataracts and feeding difficulties. Weight was 3700 g (3rd centile 5100 g), length 50.5 cm (3rd centile 58 cm), and head circumference 34.2 cm (3rd centile 39 cm). He was severely retarded, hypertonic, and hyperexcitable. Tendon reflexes were normal. There was adduction of the thumbs and pes calcaneovalgus. He also had small testes. At the age of 1 year he developed epilepsy. Laboratory investigation could not demonstrate intrauterine infection. Chromosomal analysis was normal. Plasma amino acid analysis by ion exchange chromatography and fluorescence detection revealed low fasting concentrations of serine (29 and 55; normal range for age 70-187 rnol/l) and low to normal fasting concentrations of glycine (77 and 97; 80-341 jimol/l). In the cerebrospinal fluid, protein was normal, serine was severely decreased (6; 35-80 gmol/l), and glycine was also decreased but less so (2.8; 3.6-9.0

kept at +4C0 for 4 8 hrs, for phagocytosis, candidacidal activity, chemotaxis and spont. & stim. NBT test (for methods see : Ital. J. Pediat. 4:571,1978). Phagocytosis, candidacidal activity and NBT test remained unchanged at 24 and 4 8 hrs (104% and loo%, 94% and 93%, 94% and 92% respectively of initial values). Chemotaxis only showed a slight decrease (98% and 73%). me present results show a satisfactory functional stability of PMN collected by leukafiltration, suggesting that the same concentrate may be effectively transfused for three consecutive days.

NOTE.-Phosphomannomutase and protein were measured as described elsewhere (Van Schaftingen and Jaeken 1995; Jaeken et al. 1997a). Phosphomannose isomerase was assayed at 30ЊC in a reaction mixture (1 ml) containing 50 mM Hepes, pH 7.1, 5 mM MgCl 2 , 25 mM KCl, 1 mM dithiothreitol, 0.6 mM NAD ϩ , 0.5 mM mannose 6phosphate, 2.5 U/ml glucose 6-phosphate dehydrogenase from Leuconostoc mesenteroides, and 10 mg/ml phosphoglucose isomerase with 10 ml of an extract containing 5-20 mg protein/ml. Control and PMM deficient measures are mean values ‫ע‬ SD. Where two data are given, the values were obtained on two different subcultures.