MEGALENCEPHALY AND WHITE MATTER DISEASES IN INFANCY AND CHILDHOOD
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1
Cairo university, children hospital, Pediatric Department, Egypt
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2
National research centre, Biochemical genetic unit, Egypt
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3
Ein shams university, Pediatric genetic unit, Egypt
Introduction: Canavan disease is an autosomal recessive disorder due to defective
ASPA gene responsible for the enzyme aspartoacylase leading to increase in N acetylaspartic acid in the brain & urine.
Objective: The aim of this work is to highlight the clinical manifestations of canavan disease, among cases with macrocephaly and white matter diseases, its diagnostic work up, molecular diagnosis and prenatal diagnosis
Materials & Methods: The study included twenty two cases presenting with macrocephaly &magnetic resonance imaging( MRI )findings of white matter disease & their ages ranged from 6 months - 10 years (14 males & 8 females) .All cases were subjected to full history taking ,neurological examination , fundus examination & organic acid profile in urine .Quantitative analysis of N- acetyl aspartic acid in urine was performed for( 5 cases) ,magnetic resonance spectroscopy (MRS) for( 7 cases), Aryl sulfatase activity (one case). Molecular diagnosis for Canavan disease was done for (2 cases): DNA sequence analysis of ASPA gene ( NM0049.2) & prenatal diagnosis for one pregnant mother .
Results: Accordingly cases were classified into Canavan disease 12 cases, Megalencephalic leukoencephalopathy with subcortical cysts (4 cases), Glutaric aciduria type 1 (one case), Tay sachs disease( one case),
Vanishing white matter disease ( one case) and remaining (3 cases) requires more diagnostic work up. Cases with Canavan disease ( 6ms- 54 ms) presented with psychomotor delay ,defective vision (5 cases) and seizures(7 cases). H.of first degree consanguinity was present in 5 cases, family H. of similar condition, cousins (2 cases) and H. of previous death with similar condition 2 siblings. Organic acid profile in urine showed increased N acetyl aspartate (12 cases).Quantitative determination of N acetyl aspartate in urine was very high in 5 cases. DNA sequence analysis of ASPA gene ( 2 cases) showed homozygous for c.244 dup A ( p.mct82 Asnfs X 8) mutation confirming the diagnosis of Canavan disease. Prenatal diagnosis revealed that fetus was heterozygous for c.244 dup A ( p.mct 82 Asnfs X 8) mutation, carrier for
Canavan disease
Conclusion: clinical history ,examination and MRI are important for the diagnosis of white matter diseases. Organic acid profile in urine is helpful for the diagnosis of Canavan disease and Glutaric aciduria type I.DNA sequence analysis for ASPA gene is required for the diagnosis of Canavan disease; hence prenatal diagnosis. Enzyme assay was helpful for the diagnosis of sphingolipidosis. Still some cases with leukodystrophy & macrocephaly require further work up for proper diagnosis
Acknowledgements
I would like to thank all members of the organizing team of the 4th Mediterranean Neuroscience Society 2012,Istanbul.I hope that publications help more awareness about neurodegenerative disorders ,methods of diagnosis and managements.
Keywords:
ASPA gene,
Macrocephaly,
autosomal recessive,
aspartoacylase gene,
subcortical cysts,
glutaric acid,
Prenatal Diagnosis,
homozygous,
Magnetic Resonance Imaging,
MRI,
Fundus examination,
DNA sequence,
Seizures,
N acetyl aspartic acid
Conference:
4th Conference of the Mediterrarnean Neuroscience Society, Istanbul, Türkiye, 30 Sep - 3 Oct, 2012.
Presentation Type:
Poster Presentation
Topic:
Abstracts
Citation:
Mansour
LA,
Fateen
E,
Rashed
M,
Ezzat
S,
Mohamed
S,
Badr
A and
Tarek
L
(2013). MEGALENCEPHALY AND WHITE MATTER DISEASES IN INFANCY AND CHILDHOOD.
Conference Abstract:
4th Conference of the Mediterrarnean Neuroscience Society.
doi: 10.3389/conf.fnhum.2013.210.00048
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Received:
30 Mar 2013;
Published Online:
11 Apr 2013.
*
Correspondence:
Prof. Lobna A Mansour, Cairo university, children hospital, Pediatric Department, Cairo, Cairo, 12311, Egypt, mansour_lobna@yahoo.com