Inherited Metabolic Diseases in Neurodevelopmental and Neurobehavioral Disorders
Section snippets
Guanidinoacetate Methyltransferase Deficiency
Guanidinoacetate methyltransferase (GAMT) deficiency (Online Mendelian Inheritance in Man [OMIM] + 601240) is an autosomal recessive inborn error of creatine biosynthesis. GAMT deficiency is characterized by developmental arrest or delay in the first few months of life with epilepsy and extrapyramidal movements as common features.1 Neurologic signs and symptoms are variable, and autistic spectrum disorders are sometimes seen in older affected individuals. The diagnosis of GAMT deficiency is
Succinic Semialdehyde Dehydrogenase Deficiency
Succinic semialdehyde dehydrogenase (SSADH) deficiency (OMIM #271980), also known as 4-hydroxybutyric aciduria (4-HBA), is an autosomal recessive inborn error of metabolism first described by Jakobs et al in 1981.14 Since then, over 150 cases have been identified. Clinical features include mild to severe impairment of motor skills, language, speech, and intellect. Many affected individuals also presented with hypotonia and a nonprogressive form of truncal and appendicular ataxia. The causative
Adenylosuccinate Lyase Deficiency
Adenylosuccinate lyase (ADSL) deficiency (OMIM #103050) is an autosomal recessive disorder of purine metabolism. Characteristic neurologic features include psychomotor delay, autism, and seizures.19 The associated gene is adenylosuccinate lyase (ADSL). This enzyme deficiency is characterized by increased amounts of succinyl adenosine (S-Ado) and succinyl aminoimidazole carboxamide ribotide (SAICAR) in CSF, urine, and to a lesser extent plasma. Treatment has been aimed at replenishing purine
Phosphoribosylpyrophosphate Synthetase Superactivity
Phosphoribosylpyrophosphate synthetase (PRPS1) superactivity (OMIM #300661) is an X-linked inborn error of purine metabolism with features of gout and hyperuricemia. Some individuals affected with PRPS1 superactivity also have neurodevelopmental abnormalities, including sensorineural deafness. The associated gene is phosphoribosylpyrophosphate synthetase (PRPS1). PRPS1 superactivity should be suspected in individuals with hyperuricemia, gout, mental retardation, and sensorineural deafness.
PRPS1
Dihydropyrimidine Dehydrogenase Deficiency
Dihydropyrimidine dehydrogenase (DPYS) deficiency (OMIM + 274270) is an autosomal recessive disorder of pyrimidine catabolism known also as uraciluria thyminuria. DPYS deficiency is also known as an inborn error of β-amino acid metabolism. Excess amounts of uracil, thymine, and 5-hydroxymethyluracil accumulate in the urine of affected individuals. The causative gene is dihydropyrimidine dehydrogenase (DPYS) located on chromosome 1 at 1p22. There is much phenotypic variation with DPYS
Glucose Transport Defect, Blood-Brain Barrier
Glucose transport defect of the blood-brain barrier (GLUT1 deficiency syndrome, OMIM #606777) is an autosomal dominant inborn error of glucose transport across the blood-brain barrier. Affected individuals present with mental retardation and learning disabilities; also common are ataxia, dystonia, seizures, and acquired microcephaly. The responsible gene is solute carrier member 2, family 1 (SLC2A1) located on chromosome 1 at 1p35 to 31.3. SLC2A1 encodes a facilitated glucose transporter
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Guanidinoacetate Methyltransferase DeficiencyThe Metabolic and Moleculaar Basis of Inherited Diseases
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Cited by (17)
The metabolic evaluation of the child with an intellectual developmental disorder: Diagnostic algorithm for identification of treatable causes and new digital resource
2014, Molecular Genetics and MetabolismCitation Excerpt :Treatments include dietary restriction/supplement, co-factor/-enzyme, vitamin, substrate inhibition, (small molecule) substrate reduction, enzyme replacement, bone marrow and hematopoietic stem cell transplant, and gene therapy (see Table 1 for definitions). Several reviews have been published regarding the metabolic causes of IDD, most of which are based on individual expertise in the field of IEMs [17–19]. Further, while technologies for better recognition have been introduced into clinical practice, these have yet to be incorporated into diagnostic practice recommendations or parameters for the evaluation of children with IDD, such as those of the American College of Medical Genetics (1997) [20], the American Academy of Pediatrics (2006) [21], and the American Academy of Neurology (2011) [22].
Etiological Heterogeneity in Autism Spectrum Disorders: Role of Rare Variants
2013, The Neuroscience of Autism Spectrum DisordersTreatable inborn errors of metabolism causing intellectual disability: A systematic literature review
2012, Molecular Genetics and MetabolismCitation Excerpt :Whilst current recommendations for the diagnostic work up of ID prioritise frequency of conditions and yield of diagnostic tests, our approach prioritises treatability over frequency and strategises metabolic/biochemical evaluation in a two-tiered fashion. Several reviews have been published about metabolic causes of intellectual disability, mostly reflecting expert opinions and individual expertise in the field of IEM [41–43]. The need for multiple tests to exclude a few rare to ultra-rare conditions, and the limited availabilities of laboratories offering comprehensive diagnostic testing, explains why outside highly specialised centres, metabolic work up of patients with ID is tedious, cost consuming and still remains incomplete in many cases.
Etiological Heterogeneity in Autism Spectrum Disorders: Role of Rare Variant
2012, The Neuroscience of Autism Spectrum DisordersGC/MS determination of guanidinoacetate and creatine in urine: A routine method for creatine deficiency syndrome diagnosis
2010, Clinical BiochemistryCitation Excerpt :The normal ranges are very wide in different age groups as well as for the GAA to Cr; this is explained by the fact that reference values in the population do not follow normal distribution. Clinical symptoms of defects of Cr biosynthesis and transport are not specific and induce moderate to severe mental retardation (GAMT, AGAT, SLC6A8 deficiencies), movement disorders (GAMT and SLC6A8 deficiency), autism (GAMT and AGAT deficiency), early and severe onset of epilepsy, progressive psychomotor delay (GAMT deficiency), and pallidal lesion on brain MRI (GAMT deficiency) [22,23]. Early diagnosis of these inherited metabolic diseases is essential because GAMT and AGAT deficiencies can be easily treated [24–26].
Should a metabolic work-up be performed in autism?
2010, Archives de Pediatrie