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Serine deficiency disorders are caused by a defect in one of the three synthesising enzymes of the L-serine biosynthesis pathway. Serine deficiency disorders give rise to a neurological phenotype with psychomotor retardation, microcephaly and seizures in newborns and children or progressive polyneuropathy in adult patients. There are three defects that cause serine deficiency of which 3-phosphogly
Defects in the synthesis pathways of amino acids have only been discovered in recent years and are relatively unknown to most clinicians. In this chapter disorders neurological symptoms caused by genetic defects in the synthesis of the amino acids serine, glutamine and proline are discussed. Patients with serine deficiency invariably suffer from severe neurological symptoms such as microcephaly, p
Background: Vitamin B6 is present in various forms (vitamers) in the diet that need to be metabolized to pyridoxal phosphate (PLP), the active cofactor form of vitamin B6. In literature, the liver has been reported to be the major site for this conversion, whereas the exact role of the intestine remains to be elucidated. Objective: To gain insight into the role of the intestine in human vitamin B6
Recently, d-serine has been identified as an important NMDA-receptor co-agonist, which might play a role in central nervous system development. We investigated this by studying rat P19 cells, an established model for neuronal and glial differentiation. Our results show that (1) the d-serine synthesizing enzyme serine racemase was expressed upon differentiation, (2) extracellular d-serine concentra
Case: A 34-year-old woman was referred to our hospital with progressive movement disorders and neurodegeneration with brain iron accumulation and enlargement of the frontal diploe on the MRI. Metabolic testing revealed that she had α-mannosidosis (AMD), a lysosomal storage disorder. Background: AMD is a rare genetic disorder that causes α-mannosidase deficiency resulting in lysosomal accumulation
Deficiency of ornithine-δ-aminotransferase (OAT) in humans results in gyrate atrophy. Early diagnosis may allow initiation of treatment before irreversible damage has occurred. However, diagnosis is commonly delayed well into adulthood because of the nonspecific character of initial symptoms. Here, we report findings in a neonate who was evaluated because of a positive family history of OAT defici
The neuregulin 1 (NRG1) receptor ErbB4 is involved in the development of cortical inhibitory GABAergic circuits and NRG1-ErbB4 signaling has been implicated in schizophrenia (SCZ). A magnetic resonance spectroscopy (1 H-MRS) study has demonstrated that a single-nucleotide polymorphism in ERBB4, rs7598440, influences human cortical GABA concentrations. Other work has highlighted the significant imp
BACKGROUND AND OBJECTIVE: Vitamin B6 plays a pivotal role in brain development and functioning. Differences in vitamin B6 homeostasis between preterm and term newborn infants have been reported. The authors sought to investigate whether B6 vitamers in cerebrospinal fluid (CSF) of preterm and term newborn infants are different. METHODS: B6 vitamer concentrations were determined in 69 CSF samples of
Worldwide, perinatal asphyxia is an important cause of morbidity and mortality among term-born children. Overactivation of the N-methyl-d-aspartate receptor (NMDAr) plays a central role in the pathogenesis of cerebral hypoxia-ischemia, but the role of both endogenous NMDAr co-agonists d-serine and glycine remains largely elusive. We investigated d-serine and glycine concentration changes in rat gl
A family of eukaryotic proline racemase-like genes has recently been identified. Several members of this family have been well characterized and are known to catalyze the racemization of free proline or trans-4-hydroxyproline. However, the majority of eukaryotic proline racemase-like proteins, including a human protein called C14orf149, lack a specific cysteine residue that is known to be critical
Since vitamin B6 is essential for normal functioning of the central nervous system, there is growing need for sensitive analysis of B6 vitamers in cerebrospinal fluid (CSF). This manuscript describes the development and validation of a rapid, sensitive and accurate method for quantification of the vitamin B6 vitamers pyridoxal (PL), pyridoxamine (PM), pyridoxine (PN), pyridoxic acid (PA), pyridoxa
d-Amino acids are increasingly being recognized as important signaling molecules in mammals, including humans. d-Serine and d-aspartate are believed to act as signaling molecules in the central nervous system. Interestingly, several other d-amino acids also occur in human plasma, but very little is currently known regarding their function and origin. Abnormal levels of d-amino acids have been impl
Objective: The introduction of hematopoietic stem cell transplantation (HSCT) has significantly improved the life-span of Hurler patients (mucopolysaccharidosis type I-H, MPS I-H). Yet, the musculoskeletal manifestations seem largely unresponsive to HSCT. In order to facilitate evidence based management, the aim of the current study was to give a systematic overview of the orthopaedic complication
Only recently, d-amino acids have been identified in mammals. Of these, d-serine has been most extensively studied. d-Serine was found to play an important role as a neurotransmitter in the human central nervous system (CNS) by binding to the N-methyl-d-aspartate receptor (NMDAr), similar to glycine. Therefore, d-serine may well play a role in all physiological and pathological processes in which
Aim: To determine the incidence of late intracranial vitamin K deficiency bleeding (VKDB) in The Netherlands using the Dutch Pediatric Intensive Care Evaluation (PICE) registry. Methods: The PICE registry was used to identify all infants who were admitted to a Dutch pediatric intensive care unit (PICU) with intracranial bleeding between 1 January 2004 and 31 December 2007. Cases of confirmed late
3-Phosphoglycerate dehydrogenase (3-PGDH) deficiency is considered to be a rare cause of congenital microcephaly, infantile onset of intractable seizures and severe psychomotor retardation. Here, we report for the first time a very mild form of genetically confirmed 3-PGDH deficiency in two siblings with juvenile onset of absence seizures and mild developmental delay. Amino acid analysis showed se
BACKGROUND: Hypoglycemia is one of the most common metabolic derangements in childhood. To establish the cause of hypoglycemia, fasting tolerance tests can be used. Currently available reference values for fasting tolerance tests have limitations in their use in daily practice. OBJECTIVE: The aim of this study was to determine the reference values of metabolites involved in glucose homeostasis dur
There are a few studies that report cognitive impairment as a complication of treatment with beta- blockers. We aimed to evaluate the longitudinal association between use of beta-blockers, as a class, and incident risk of all-cause dementia, vascular dementia, Alzheimer's and mixed dementia in the prospective population-based Malmö Preventive Project. We included 18,063 individuals (mean age 68.2,
Orthostatic hypotension (OH) is associated with increased risk of trauma and cardiovascular events. Recent studies have identified new genetic variants that influence orthostatic blood pressure (BP). The aim of this study was to investigate the associations of candidate gene loci with orthostatic BP responses in older adults. A total of 3,430 participants aged ≥50 years from The Irish Longitudinal
Background: Certain immunoglobulins (Ig) are proposed to have protective functions in atherosclerosis.Objectives: We tested whether serum levels of IgG and IgM autoantibodies against malondialdehyde low density lipoprotein (MDA-LDL) are associated with clinical coronary heart disease (CHD) and unfavorable plaque characteristics.Methods: NORDIL was a prospective study investigating adverse cardiova
