In this paper, we describe a distinct clinical subtype of 3-methylglutaconic aciduria. 3-Methylglutaconic aciduria is a group of different metabolic disorders biochemically characterized by increased urinary excretion of 3-methylglutaconic acid. We performed biochemical and genetic investigations, including urine organic acid analysis, NMR spectroscopy, measurement of 3-methylglutaconyl-CoA hydrat

In a previous study, Dutch children with phenylketonuria (PKU) were found to be slightly shorter than their healthy counterparts. In the literature, it has been hypothesized that a higher protein intake is necessary to optimize growth in PKU patients. The study aimed to investigate whether protein intake (total, natural and protein substitute) in this group might be an explanatory factor for the o

We describe two unrelated cases of ornithine aminotransferase (OAT) deficiency with rare neonatal presentation of hyperammonaemia. The diagnosis in the neonatal presentation of OAT deficiency is hampered as hyperornithinaemia is absent. Enzyme and mutation studies confirmed the diagnosis. OAT deficiency should be included in differential diagnosis of neonatal hyperammonaemia.

Background: Multiple Acyl-CoA-Dehydrogenase deficiency (MADD) is an inherited metabolic disorder characterized by impaired oxidation of fatty acids and some amino acids. Methods: We were interested whether children with MADD could tolerate a prolonged low-intensity exercise test and if this test could have any additional diagnostic value. Therefore, we performed a maximal exercise test and a low-i

Recent evidence has shown that D-amino acids are present in animals and humans in high concentrations and fulfill specific biological functions. In the central nervous system, two D-amino acids, D-serine and D-aspartate, occur in considerable concentrations. D-Serine is synthesized and metabolized endogenously and the same might account for D-aspartate. D-Serine has been studied most extensively a

We present a newborn with glutathione synthetase deficiency and intracranial haemorrhages. Because the latter are rare in term newborns a possible relationship with glutathione synthetase deficiency will be discussed.

We report two siblings with a mitochondrial respiratory chain defect who presented with progressive bulbar paralysis of childhood (Fazio-Londe disease). Mitochondrial respiratory chain defects should be considered in the differential diagnosis of this rare clinical entity.

Purpose of review: Serine-deficiency disorders comprise a new group of neurometabolic diseases and are caused by defects in the biosynthesis of the amino acid L-serine. In contrast to most neurometabolic disorders, serine-deficiency disorders are potentially treatable. Furthermore, the severe neurological symptoms observed in patients underscore the important roles of the serine biosynthetic pathw

Resting energy expenditure (REE) was investigated in 8 children with propionic and methylmalonic acidaemias because a lowered REE has been reported in the literature. We observed a marginally elevated REE and think that adequate caloric intake and the use of a synthetic amino acid mixture are responsible for this.

The molecular nature of a severe multisystemic disorder with a recurrent nonimmune hydrops fetalis was identified as deficiency of GDP-Man:GlcNAc 2-PP-dolichol mannosyltransferase, the human orthologue of the yeast ALG1 gene (MIM 605907). The disease belongs to the group of congenital disorders of glycosylation (CDG) and is designated as subtype CDG-Ik. In patient-derived serum, the total amount o

Serine-synthesis disorders have recently been described as a new group of inborn errors of metabolism due to a deficiency of the amino acid serine. Until now two defects have been reported, first 3-fosfoglycerate dehydrogenase (3-PGDH) deficiency and secondly 3-fosfoserine phosphatase (3-PSP) deficiency. Both disorders present with congenital microcephaly, severe psychomotor retardation and in 3-P

The amino acid L-serine, one of the so-called non-essential amino acids, plays a central role in cellular proliferation. L-Serine is the predominant source of one-carbon groups for the de novo synthesis of purine nucleotides and deoxythymidine monophosphate. It has long been recognized that, in cell cultures, L-serine is a conditional essential amino acid, because it cannot be synthesized in suffi

Vitamin K deficiency in infants can cause life-threatening haemorrhages. To prevent this, neonates in the Netherlands receive an oral dose of 1 mg vitamin K directly after birth. In addition, because breast milk contains little vitamin K, breast-fed infants receive a daily dose of 25 μg the first three months. Of three female infants aged 4 weeks, 5 months and 3 months, respectively, two developed

We reviewed our data on patients in whom plasma pipecolic acid was analysed. Mild to moderate elevations of pipecolic acid were frequently found in non-peroxisomal disorders and this should be taken into account when interpreting the laboratory data.

Glutaric aciduria type III is a rare metabolic abnormality leading to persistent isolated glutaric acid excretion. We report the clinical and biochemical phenotypes of three affected children. The first patient is a boy with dysmorphic features and a chromosomal deletion (monosomy 6q26-qter) in whom a persistent glutaric aciduria (500mmol/mol creatinine, normal

Congenital microcephaly, intractable seizures and severe psychomotor retardation characterize 3-phosphoglycerate dehydrogenase (3-PGDH) deficiency, a disorder of L-serine biosynthesis. The enzyme defect results in low concentrations of serine and to a variable degree of glycine in plasma and cerebrospinal fluid. Short-term beneficial effects have been reported of oral treatment with the deficient

Four neonates with a positive phenylalanine screening test (Phe concentrations between 258 and 1250 μmol/L) were investigated further to differentiate between phenylalanine hydroxylase (PAH) deficiency and variant hyperphenylalaninaemia (HPA) forms. In patients 1 and 2 a tetrahydrobiopterin (BH 4) load caused a significant decrease of the plasma Phe levels. A combined phenylalanine/BH 4 loading te