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Abstract

Neuronal ceroid lipofuscinosis is a severe neurodegenerative lysosomal storage disorder. Gamma-aminobutyric acid and glutamate deficiency have been reported with CLN1, CLN3, and CLN6. Isolated biopterin/neopterin without dopamine deficiency has been reported in 1 patient with a CLN2 mutation. This report describes a patient with a CLN2 mutation with symptomatic biopterin and dopamine deficiency. A 4-year-old boy presented with intractable epilepsy and developmental regression starting 1 year previously. His exam showed retinopathy, scanning speech, dysmetria, and ataxic fenestrating gait with stooped posture. Electroencephalogram showed generalized spikes with occipital spikes on slow photic stimulation. Brain magnetic resonance images 1 year apart showed significant diffuse atrophy. CLN2 gene sequencing showed pathogenic compound heterozygous mutations. Cerebrospinal fluid neurotransmitters showed low homovanillic acid and tetrahydrobiopterin. Levodopa-carbidopa resulted in dramatic improvement of gait. Dopamine/biopterin deficiency is a possible secondary manifestation of CLN2 mutations. Levodopa and dopamine agonists might be useful in treating these secondary abnormalities and improving quality of life in these patients.

Keywords

epilepsy neuronal ceroid lipofuscinosis neurotransmitter dopamine bioprotein lysosomal disorder

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References

Rider

DL.

Batten disease, a twenty-eight-year struggle: past, present and future. Neuropediatrics. 1997;28:4–5.

Zhong

Neuronal ceroid lipofuscinoses and possible pathogenic mechanism. Mol Genet Metab. 2000;71:195–206.

Haltia

The neuronal ceroid-lipofuscinoses: from past to present. Biochim Biophys Acta. 2006;1762:850–856.

Jalanko

Braulke

Neuronal ceroid lipofuscinoses. Biochim Biophys Acta. 2009;1793:697–709.

Kohlschutter

Schulz

Towards understanding the neuronal ceroid lipofuscinoses. Brain Dev. 2009;31:499–502.

Mole

SE.

Neuronal ceroid lipofuscinoses (NCL). Eur J Paediatr Neurol. 2006;10:255–257.

Pierret

Morrison

Kirk

MD.

Treatment of lysosomal storage disorders: focus on the neuronal ceroid-lipofuscinoses. Acta Neurobiol Exp (Wars). 2008;68:429–442.

Siintola

Lehesjoki

Mole

SE.

Molecular genetics of the NCLs—status and perspectives. Biochim Biophys Acta. 2006;1762:857–864.

Williams

Aberg

Autti

. Diagnosis of the neuronal ceroid lipofuscinoses: an update. Biochim Biophys Acta. 2006;1762:865–872.

10.

Wronska

Moroziewicz

. Genotype-phenotype analyses of classic neuronal ceroid lipofuscinosis (NCLs): genetic predictions from clinical and pathological findings. Beijing Da Xue Xue Bao. 2006;38:41–48.

11.

Bonafe

Thony

Penzien

. Mutations in the sepiapterin reductase gene cause a novel tetrahydrobiopterin-dependent monoamine-neurotransmitter deficiency without hyperphenylalaninemia. Am J Hum Genet. 2001;69:269–277.

12.

Giovanniello

Leuzzi

Carducci

. Tyrosine hydroxylase deficiency presenting with a biphasic clinical course. Neuropediatrics. 2007;38:213–215.

13.

Marin-Valencia

Serrano

Ormazabal

. Biochemical diagnosis of dopaminergic disturbances in paediatric patients: analysis of cerebrospinal fluid homovanillic acid and other biogenic amines. Clin Biochem. 2008;41:1306–1315.

14.

Pearl

Taylor

Trzcinski

Sokohl

The pediatric neurotransmitter disorders. J Child Neurol. 2007;22:606–616.

15.

van den

Heuvel LP

Luiten

Smeitink

. A common point mutation in the tyrosine hydroxylase gene in autosomal recessive L-DOPA-responsive dystonia in the Dutch population. Hum Genet. 1998;102:644–646.

16.

Sitter

Autti

Tyynela

. High-resolution magic angle spinning and 1H magnetic resonance spectroscopy reveal significantly altered neuronal metabolite profiles in CLN1 but not in CLN3. J Neurosci Res. 2004;77:762–769.

17.

Pears

Cooper

Mitchison

. High resolution 1H NMR-based metabolomics indicates a neurotransmitter cycling deficit in cerebral tissue from a mouse model of Batten disease. J Biol Chem. 2005;280:42508–42514.

18.

Weimer

Benedict

Elshatory

. Alterations in striatal dopamine catabolism precede loss of substantia nigra neurons in a mouse model of juvenile neuronal ceroid lipofuscinosis. Brain Res. 2007;1162:98–112.

19.

Rinne

Ruottinen

Nagren

. Positron emission tomography shows reduced striatal dopamine D1 but not D2 receptors in juvenile neuronal ceroid lipofuscinosis. Neuropediatrics. 2002;33:138–141.

20.

Ruottinen

Rinne

Haaparanta

. 18F]fluorodopa PET shows striatal dopaminergic dysfunction in juvenile neuronal ceroid lipofuscinosis. J Neurol Neurosurg Psychiatry. 1997;62:622–625.

21.

Oswald

Palmer

Kay

. Location and connectivity determine GABAergic interneuron survival in the brains of South Hampshire sheep with CLN6 neuronal ceroid lipofuscinosis. Neurobiol Dis. 2008;32:50–65.

22.

Pears

Salek

Palmer

. Metabolomic investigation of CLN6 neuronal ceroid lipofuscinosis in affected South Hampshire sheep. J Neurosci Res. 2007;85:3494–3504.

23.

Barisic

Logan

Pikija

. R208X mutation in CLN2 gene associated with reduced cerebrospinal fluid pterins in a girl with classic late infantile neuronal ceroid lipofuscinosis. Croat Med J. 2003;44:489–493.

24.

Aberg

Rinne

Rajantie

Santavuori

A favorable response to antiparkinsonian treatment in juvenile neuronal ceroid lipofuscinosis. Neurology. 2001;56:1236–1239.

Late Infantile Neuronal Ceroid Lipofuscinosis and Dopamine Deficiency

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