In a patient with extrapyramidal movement disorder and extremely low creatinine concentrations in serum and urine, in vivo proton magnetic resonance spectroscopy disclosed a generalized depletion of creatinine in the brain. Oral substitution of arginine, a substrate for creatine synthesis, resulted in an increase of brain guanidinoacetate as the immediate precursor of creatine but did not elevate cerebral creatine levels. In contrast, oral substitution of creatine-monohydrate led to a significant increase of brain creatine, a decrease of brain guanidinoacetate, and a normalization of creatinine in serum and urine. Phosphorus magnetic resonance spectroscopy of the brain revealed no detectable creatine-phosphate before oral substitution of creatine and a significant increase afterward. Partial restoration of cerebral creatine concentrations was accompanied by improvement of the patient's neurologic symptoms. This is the first report of a patient with complete creatine deficiency in the brain. Magnetic resonance spectroscopy during arginine and creatine treatment point to an inborn error of creatine biosynthesis at the level of guanidinoacetete-methyltransferase.

Amongst 21 children with unclassified white matter diseases three patients could be characterised by an identical clinical picture, magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) findings as a probably distinct entity. Following a normal early development they later showed rapidly progressive motor symptoms (ataxia, spasticity) leading to severe handicap within one or two years after onset. Later on bulbar symptoms, optic atrophy and epileptic seizures occurred. The MRI showed a diffuse homogeneous hypodensity of the white matter almost identical to the signal of the ventricles. MRS revealed a near total absence of N-acetylaspartate, choline and creatine and an increase of lactate and glucose. One girl and one boy were siblings, indicating an autosomal recessive trait.

Deficiency of dolichyl-P-Glc:Man 9 GlcNAc 2 -PP-dolichyl glucosyltransferase is the cause of an additional type of carbohydrate-deficient glycoprotein syndrome (CDGS type V). Clinically this type resembles the classical type Ia of CDGS caused by the deficiency of phosphomannomutase. Carbohydrate-deficient glycoprotein syndromes (CDGS) are a family of disorders in which the glycosylation of glycoproteins is abnormal. Clinically the patients suffer from severe psychomotoric and mental retardation, dysmorphism, coagulation abnormalities, and dysfunction of many organs (1, 2). The clinical manifestations, however, are heterogeneous, and one form of CDGS is known (CDGS type 1b) that lacks neurologic symptoms and dysmorphism and presents as a hepatogastrointestinal disorder (3). The defective glycosylation usually is recognized by isoelectric focusing of serum glycoproteins such as transferrin and involves incomplete utilization of Nglycosylation sites and͞or the presence of abnormal oligosaccharide side chains. The majority of patients with CDGS have a deficiency of phosphomannomutase (CDGS type Ia) (4, 5). Less common are deficiencies of phosphomannose isomerase (type Ib) (3, 6) or of N-acetylglucosaminyltransferase II (type II) (7,8) as the cause of CDGS. The basic defect in type III (9) and type IV (10) of CDGS is unknown so far.In this paper, we describe the defect in an additional type of CDGS (type V), which clinically resembles the classical type Ia caused by phosphomannomutase deficiency. In CDGS type V, the glucosyltransferase that transfers glucose from dolichyl phosphate glucose (Dol-P-Glc) onto the lipid-linked oligosaccharide (LLO) Man 9 GlcNAc 2 -PP-Dol is deficient. The defect is leaky and allows for a residual synthesis of glucosylated forms of LLOs, which are known to be the preferred substrate of oligosaccharyltransferase (11-16). The biochemical phenotype of CDGS type V is characterized by an accumulation on nonglucosylated LLOs, a marked reduction of glucosylated LLOs, and incomplete utilization of N-glycosylation sites in nascent glycoproteins.