Hepatocerebral form of mitochondrial DNA depletion syndrome: novel MPV17 mutations.
BACKGROUND
Autosomal recessive mutations in MPV17 (OMIM *137960) have been identified in the hepatocerebral form of mitochondrial DNA depletion syndrome (MDS).


OBJECTIVE
To describe the clinical, morphologic, and genetic findings in 3 children with MPV17-related MDS from 2 unrelated families.


METHODS
Case report.


METHODS
Academic research.


METHODS
We identified 3 novel pathogenic mutations in 3 children.


RESULTS
Two children were homozygous for nonsense mutation p.W120X. A third child was compound heterozygous for missense mutation p.G24W and for a macrodeletion spanning MPV17 exon 8. All patients demonstrated lactic acidosis, hypoglycemia, hepatomegaly, and progressive liver failure. Neurologic symptoms manifested at a later stage of the disease. Death occurred within the first year of life in all 3 patients.


CONCLUSIONS
These data confirm that MPV17 mutations are associated with a 2-stage syndrome. The first symptoms are metabolic and rapidly progress to hepatic failure. This stage is followed by neurologic involvement affecting the central and peripheral systems.
Spinazzola
Antonella
A
Unit of Molecular Neurogenetics, Pierfranco and Luisa Mariani Center, Study of Children's Mitochondrial Disorders, C Besta Neurological Institute Foundation, Milano, Italy.
Santer
René
R
Akman
Orhan H
OH
Tsiakas
Kostas
K
Schaefer
Hansjoerg
H
Ding
Xiaoqi
X
Karadimas
Charalampos L
CL
Shanske
Sara
S
Ganesh
Jaya
J
Di Mauro
Salvatore
S
Zeviani
Massimo
M
D001928:Brain Diseases, Metabolic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018389:Codon, Nonsense / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D005808:Genes, Recessive; D054629:Genome, Mitochondrial / Q000235:genetics; D006801:Humans; D007223:Infant; D017093:Liver Failure / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics*; D008661:Metabolism, Inborn Errors / Q000235:genetics; D028361:Mitochondrial Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D024101:Mitochondrial Proteins / Q000172:deficiency* / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics*; D013577:Syndrome
D018389:Codon, Nonsense; D004272:DNA, Mitochondrial; C530370:MPV17 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins