Abstract
Background: Two unrelated girls had early onset of nystagmus and epilepsy, absent psychomotor development, and almost complete absence of myelin on cerebral MRI. The clinical features and MR images of both patients resembled the connatal form of Pelizaeus-Merzbacher disease (PMD), which is an X-linked recessive disorder caused by duplications or mutations of the proteolipid protein gene (PLP). Objective: To define a unique neurometabolic disorder with failure of myelination. Methods and Results: 1H-NMR of CSF in both girls was performed repeatedly, and both showed highly elevated concentrations of N-acetylaspartylglutamate (NAAG). The coding sequence of the gene coding for glutamate carboxypeptidase II, which converts NAAG to N-acetylaspartate (NAA) and glutamate, was entirely sequenced but revealed no mutations. Even though both patients are girls, the authors sequenced the PLP gene and found no abnormality. Conclusions: NAAG is an abundant peptide neurotransmitter whose exact role is unclear. NAAG is implicated in two cases of unresolved severe CNS disorder. Its elevated concentration in CSF may be the biochemical hallmark for a novel neurometabolic disorder. The cause of its accumulation is still unclear.
| Original language | English |
|---|---|
| Pages (from-to) | 1503-1508 |
| Number of pages | 6 |
| Journal | Neurology |
| Volume | 62 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 11 May 2004 |
Cite this
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Severe hypomyelination associated with increased levels of N-acetylaspartylglutamate in CSF. / Wolf, N. I.; Willemsen, M. A.A.P.; Engelke, U. F.; Van Der Knaap, M. S.; Pouwels, P. J.W.; Harting, I.; Zschocke, J.; Sistermans, E. A.; Rating, D.; Wevers, R. A.
In: Neurology, Vol. 62, No. 9, 11.05.2004, p. 1503-1508.Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Severe hypomyelination associated with increased levels of N-acetylaspartylglutamate in CSF
AU - Wolf, N. I.
AU - Willemsen, M. A.A.P.
AU - Engelke, U. F.
AU - Van Der Knaap, M. S.
AU - Pouwels, P. J.W.
AU - Harting, I.
AU - Zschocke, J.
AU - Sistermans, E. A.
AU - Rating, D.
AU - Wevers, R. A.
PY - 2004/5/11
Y1 - 2004/5/11
N2 - Background: Two unrelated girls had early onset of nystagmus and epilepsy, absent psychomotor development, and almost complete absence of myelin on cerebral MRI. The clinical features and MR images of both patients resembled the connatal form of Pelizaeus-Merzbacher disease (PMD), which is an X-linked recessive disorder caused by duplications or mutations of the proteolipid protein gene (PLP). Objective: To define a unique neurometabolic disorder with failure of myelination. Methods and Results: 1H-NMR of CSF in both girls was performed repeatedly, and both showed highly elevated concentrations of N-acetylaspartylglutamate (NAAG). The coding sequence of the gene coding for glutamate carboxypeptidase II, which converts NAAG to N-acetylaspartate (NAA) and glutamate, was entirely sequenced but revealed no mutations. Even though both patients are girls, the authors sequenced the PLP gene and found no abnormality. Conclusions: NAAG is an abundant peptide neurotransmitter whose exact role is unclear. NAAG is implicated in two cases of unresolved severe CNS disorder. Its elevated concentration in CSF may be the biochemical hallmark for a novel neurometabolic disorder. The cause of its accumulation is still unclear.
AB - Background: Two unrelated girls had early onset of nystagmus and epilepsy, absent psychomotor development, and almost complete absence of myelin on cerebral MRI. The clinical features and MR images of both patients resembled the connatal form of Pelizaeus-Merzbacher disease (PMD), which is an X-linked recessive disorder caused by duplications or mutations of the proteolipid protein gene (PLP). Objective: To define a unique neurometabolic disorder with failure of myelination. Methods and Results: 1H-NMR of CSF in both girls was performed repeatedly, and both showed highly elevated concentrations of N-acetylaspartylglutamate (NAAG). The coding sequence of the gene coding for glutamate carboxypeptidase II, which converts NAAG to N-acetylaspartate (NAA) and glutamate, was entirely sequenced but revealed no mutations. Even though both patients are girls, the authors sequenced the PLP gene and found no abnormality. Conclusions: NAAG is an abundant peptide neurotransmitter whose exact role is unclear. NAAG is implicated in two cases of unresolved severe CNS disorder. Its elevated concentration in CSF may be the biochemical hallmark for a novel neurometabolic disorder. The cause of its accumulation is still unclear.
UR - http://www.scopus.com/inward/record.url?scp=2342659631&partnerID=8YFLogxK
U2 - 10.1212/01.WNL.0000123094.13406.20
DO - 10.1212/01.WNL.0000123094.13406.20
M3 - Article
VL - 62
SP - 1503
EP - 1508
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 9
ER -