Lysine Restriction and Pyridoxal Phosphate Administration in a NADK2 Patient

We report the case of a 10-year-old Spanish girl with mutations in NADK2 Prenatal central nervous system abnormalities showed ventriculomegaly, colpocephaly, and hypoplasia of the corpus callosum. At birth, axial hypotonia, uncoordinated movements, microcephaly, and generalized cerebellar atrophy we...

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Bibliographic Details
Published in:Pediatrics (Evanston) 2016-11, Vol.138 (5), p.e1
Main Authors: Tort, Frederic, Ugarteburu, Olatz, Torres, Maria Angeles, García-Villoria, Judit, Girós, Marisa, Ruiz, Angeles, Ribes, Antonia
Format: Article
Language:English
Subjects:
Amino acids
Child
Diet
Dietary supplements
Epilepsies, Myoclonic - genetics
Epilepsies, Myoclonic - therapy
Female
Genes
Homozygote
Humans
Hyperlysinemias - genetics
Lactic Acid - blood
Lactic Acid - cerebrospinal fluid
Lysine - administration & dosage
Lysine - blood
Lysine - cerebrospinal fluid
Mitochondrial Diseases - genetics
Mitochondrial Proteins - genetics
Mutation
Nervous System Malformations - genetics
Pediatrics
Phosphotransferases (Alcohol Group Acceptor) - genetics
Pipecolic Acids - blood
Pipecolic Acids - cerebrospinal fluid
Pyridoxal Phosphate - therapeutic use
RNA, Messenger - metabolism
Vitamin B
Vitamin B Complex - therapeutic use
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Summary:We report the case of a 10-year-old Spanish girl with mutations in NADK2 Prenatal central nervous system abnormalities showed ventriculomegaly, colpocephaly, and hypoplasia of the corpus callosum. At birth, axial hypotonia, uncoordinated movements, microcephaly, and generalized cerebellar atrophy were detected. Metabolic investigations revealed high lysine, lactate, and pipecolic acid levels in blood and cerebrospinal fluid. Pyruvate carboxylase and pyruvate dehydrogenase activity in fibroblasts were normal. Beginning at birth she received biotin, thiamine, and carnitine supplementation. A lysine-restricted diet was started when she was 1 month old. Because pipecolic acid was high, pyridoxine was added to treatment. At 3 years old, astatic myoclonic epilepsy appeared, with no response to levetiracetam. We switched pyridoxine to pyridoxal phosphate, with electroclinical improvement. Because the activity of mitochondrial respiratory chain complexes III and IV was slightly low in muscle, other cofactors such as ubidecarenone, idebenone, vitamin E, and creatine were added to the treatment. At 8 years old, plasma acylcarnitine testing was performed, and high levels of 2-trans, 4-cis-decadienoylcarnitine were found. Whole exome sequencing identified a homozygous splice site mutation in NADK2 (c.956+6T>C; p.Trp319Cysfs*21). This substitution generates exon skipping, leading to a truncated protein. In fact, NADK2 messenger RNA and the corresponding protein were almost absent. Now, at 10 years of age she presents with ataxia and incoordination. She has oromotor dysphasia but is able to understand fluid language and is a very friendly girl. We hypothesize that the patient's clinical improvement could be due to her lysine-restricted diet together with cofactors and pyridoxal phosphate administration.
ISSN:0031-4005
1098-4275
DOI:10.1542/peds.2015-4534