Hepatocerebral form of mitochondrial DNA depletion syndrome: novel MPV17 mutations.
Standard
Hepatocerebral form of mitochondrial DNA depletion syndrome: novel MPV17 mutations. / Spinazzola, Antonella; Santer, René; Akman, Orhan H; Tsiakas, Kostas Konstantinos; Schaefer, Hansjoerg; Ding, Xiaoqi; Karadimas, Charalampos L; Shanske, Sara; Ganesh, Jaya; Salvatore, Di Mauro; Zeviani, Massimo.
In: ARCH NEUROL-CHICAGO, Vol. 65, No. 8, 8, 2008, p. 1108-1113.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Hepatocerebral form of mitochondrial DNA depletion syndrome: novel MPV17 mutations.
AU - Spinazzola, Antonella
AU - Santer, René
AU - Akman, Orhan H
AU - Tsiakas, Kostas Konstantinos
AU - Schaefer, Hansjoerg
AU - Ding, Xiaoqi
AU - Karadimas, Charalampos L
AU - Shanske, Sara
AU - Ganesh, Jaya
AU - Salvatore, Di Mauro
AU - Zeviani, Massimo
PY - 2008
Y1 - 2008
N2 - 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. DESIGN: Case report. SETTING: Academic research. MAIN OUTCOME MEASURES: 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.
AB - 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. DESIGN: Case report. SETTING: Academic research. MAIN OUTCOME MEASURES: 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 65
SP - 1108
EP - 1113
IS - 8
M1 - 8
ER -
