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A Patient with Complex I Deficiency Caused by a Novel ACAD9 Mutation Not Responding to Riboflavin Treatment

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@article{4a88470eaf30498da81f1ed2760e133d,
title = "A Patient with Complex I Deficiency Caused by a Novel ACAD9 Mutation Not Responding to Riboflavin Treatment",
abstract = "Here we report a patient with a new pathogenic mutation in ACAD9. Shortly after birth she presented with respiratory insufficiency and a high lactate level. At age 7 weeks, she was diagnosed with severe hypertrophic cardiomyopathy and she suffered from muscle weakness and hypotonia. Her condition deteriorated during intercurrent illnesses and she died at 6 months of age in cardiogenic shock. Analysis of respiratory chain activities in muscle and fibroblasts revealed an isolated complex I deficiency. A genome-wide screen for homozygosity revealed several homozygous regions. Four candidate genes were found and sequencing revealed a homozygous missense mutation in ACAD9. The mutation results in an Ala220Val amino acid substitution located near the catalytic core of ACAD9. SDS and BN-PAGE analysis showed severely decreased ACAD9 and complex I protein levels, and lentiviral complementation of patient fibroblasts partially rescued the complex I deficiency. Riboflavin supplementation did not ameliorate the complex I deficiency in patient fibroblasts. More than a dozen ACAD9 patients with complex I deficiency have been identified in the last 3 years, indicating that ACAD9 is important for complex I assembly, and that ACAD9 mutations are a relatively frequent cause of complex I deficiency.",
author = "Jessica Nouws and Flemming Wibrand and {van den Brand}, Mari{\"e}l and Hanka Venselaar and Morten Duno and Lund, {Allan M} and Simon Trautner and Leo Nijtmans and Elsebet {\O}stergaard",
year = "2014",
doi = "10.1007/8904_2013_242",
language = "English",
volume = "12",
pages = "37--45",
journal = "JIMD Reports",
issn = "2192-8304",
publisher = "Springer Berlin",

}

RIS

TY - JOUR

T1 - A Patient with Complex I Deficiency Caused by a Novel ACAD9 Mutation Not Responding to Riboflavin Treatment

AU - Nouws, Jessica

AU - Wibrand, Flemming

AU - van den Brand, Mariël

AU - Venselaar, Hanka

AU - Duno, Morten

AU - Lund, Allan M

AU - Trautner, Simon

AU - Nijtmans, Leo

AU - Østergaard, Elsebet

PY - 2014

Y1 - 2014

N2 - Here we report a patient with a new pathogenic mutation in ACAD9. Shortly after birth she presented with respiratory insufficiency and a high lactate level. At age 7 weeks, she was diagnosed with severe hypertrophic cardiomyopathy and she suffered from muscle weakness and hypotonia. Her condition deteriorated during intercurrent illnesses and she died at 6 months of age in cardiogenic shock. Analysis of respiratory chain activities in muscle and fibroblasts revealed an isolated complex I deficiency. A genome-wide screen for homozygosity revealed several homozygous regions. Four candidate genes were found and sequencing revealed a homozygous missense mutation in ACAD9. The mutation results in an Ala220Val amino acid substitution located near the catalytic core of ACAD9. SDS and BN-PAGE analysis showed severely decreased ACAD9 and complex I protein levels, and lentiviral complementation of patient fibroblasts partially rescued the complex I deficiency. Riboflavin supplementation did not ameliorate the complex I deficiency in patient fibroblasts. More than a dozen ACAD9 patients with complex I deficiency have been identified in the last 3 years, indicating that ACAD9 is important for complex I assembly, and that ACAD9 mutations are a relatively frequent cause of complex I deficiency.

AB - Here we report a patient with a new pathogenic mutation in ACAD9. Shortly after birth she presented with respiratory insufficiency and a high lactate level. At age 7 weeks, she was diagnosed with severe hypertrophic cardiomyopathy and she suffered from muscle weakness and hypotonia. Her condition deteriorated during intercurrent illnesses and she died at 6 months of age in cardiogenic shock. Analysis of respiratory chain activities in muscle and fibroblasts revealed an isolated complex I deficiency. A genome-wide screen for homozygosity revealed several homozygous regions. Four candidate genes were found and sequencing revealed a homozygous missense mutation in ACAD9. The mutation results in an Ala220Val amino acid substitution located near the catalytic core of ACAD9. SDS and BN-PAGE analysis showed severely decreased ACAD9 and complex I protein levels, and lentiviral complementation of patient fibroblasts partially rescued the complex I deficiency. Riboflavin supplementation did not ameliorate the complex I deficiency in patient fibroblasts. More than a dozen ACAD9 patients with complex I deficiency have been identified in the last 3 years, indicating that ACAD9 is important for complex I assembly, and that ACAD9 mutations are a relatively frequent cause of complex I deficiency.

U2 - 10.1007/8904_2013_242

DO - 10.1007/8904_2013_242

M3 - Journal article

VL - 12

SP - 37

EP - 45

JO - JIMD Reports

JF - JIMD Reports

SN - 2192-8304

ER -

ID: 42979504