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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 <10) was detected during a routine m
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
