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

White matter abnormalities are a feature of many inborn errors of metabolism and magnetic resonance imaging (MRI) of the brain has become an important tool in the diagnostic workup of these disorders. Recently, patients were reported with a potentially treatable disorder of serine biosynthesis. They presented with congenital microcephaly, severe psychomotor retardation and intractable seizures. Lo

During the last few years, progress in identifying the molecular defects of the carbohydrate-deficient glycoprotein syndromes has been very rapid. Up to this date, six different gene defects have been elucidated. The plethora of defects that will eventually be identified makes it indispensable to use a simple and straightforward nomenclature for this group of diseases. A group of specialists in th

Mevalonic aciduria is an inborn error of cholesterol and nonsterol isoprene biosynthesis due to mevalonate kinase deficiency (MKD; McKusick 251170). Urinary excretion of mevalonate is massively increased. Clinical manifestations include psychomotor retardation, hypotonia, dysmorphic features, failure to thrive, cataracts and hepatosplenomegaly. In addition to the multisystemic symptoms, patients p

Congenital hepatic fibrosis is a rare disorder of intrahepatic bile ducts with the persistence of embryological bile duct structures in ductal plate configuration. Three siblings aged 18, 17 and 14 years old were found to have congenital hepatic fibrosis associated with a deficiency of the enzyme phosphomannose isomerase. The clinical symptoms were recurrent attacks of persistent vomiting with dia

CDG-Ib is the 'gastro-intestinal' type of the congenital disorders of glycosylation (CDG) and a potentially treatable disorder. It has been described in patients presenting with congenital hepatic fibrosis and protein losing enteropathy. The symptoms result from hypoglycosylation of serum and other glycoproteins. CDG-Ib is caused by a deficiency of mannose-6-phosphate isomerase (synonym: phosphoma

3-phosphoglycerate dehydrogenase (PHGDH) deficiency is a disorder of L-serine biosynthesis that is characterized by congenital microcephaly, psychomotor retardation, and seizures. To investigate the molecular basis for this disorder, the PHGDH mRNA sequence was characterized, and six patients from four families were analyzed for sequence variations. Five patients from three different families were

During the last few years, progress in identifying the molecular defects of the carbohydrate-deficient glycoprotein syndromes has been very rapid. Up to this date, six different gene defects have been elucidated. The plethora of defects that will eventually be identified makes it indispensable to use a simple and straightforward nomenclature for this group of diseases. A group of specialists in th

Pontocerebellar hypoplasias are congenital disorders of brain morphogenesis which include such diverse etiologies as carbohydrate-deficient glycoprotein syndrome type 1, cerebromuscular dystrophies (Walker-Warburg syndrome, Fukuyama syndrome, muscle-eye-brain disease) and at least two types of autosomal recessive neurodegenerations known as pontocerebellar hypoplasia type I and II. Pontocerebellar

Hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS; MIM 260920) is an autosomal recessive disorder characterized by recurrent episodes of fever associated with lymphadenopathy, arthralgia, gastrointestinal dismay and skin rash. Diagnostic hallmark of HIDS is a constitutively elevated level of serum immunoglobulin D (IgD), although patients have been reported with normal IgD levels. To de

Serine deficiency disorders comprise a new group of inborn errors of serine metabolism. Patients affected with these disorders present with major neurological symptoms including congenital microcephaly, seizures, psychomotor retardation or polyneuropathy. The diagnosis of serine deficiency is based on the detection of low concentrations of the amino acids serine and glycine in fasted plasma and ce

Three siblings suffered from an unusual disorder of cyclic vomiting and congenital hepatic fibrosis. Serum transferrin isoelectric focusing showed increased asialo- and disialotransferrin isoforms as seen in the carbohydrate-deficient glycoprotein (CDG) syndrome type I. Phosphomannomutase, which is deficient in most patients with type I CDG syndrome, was found to be normal in all three patients. S