Abstract:
:We present a 32-year-old patient who, from age 7 months, developed photophobia, left-eye ptosis and progressive muscular weakness. At age 7 years, she showed normal psychomotor development, bilateral ptosis and exercise-induced weakness with severe acidosis. Basal blood and urine lactate were normal, increasing dramatically after effort. PDHc deficiency was demonstrated in muscle and fibroblasts without detectable PDHA1 mutations. Ketogenic diet was ineffective, however thiamine gave good response although bilateral ptosis and weakness with acidosis on exercise persisted. Recently, DLD gene analysis revealed a homozygous missense mutation, c.1440 A>G (p.I480M), in the interface domain. Both parents are heterozygous and DLD activity in the patient's fibroblasts is undetectable. The five patients that have been reported with DLD-interface mutations suffered fatal deteriorations. Our patient's disease is milder, only myopathic, more similar to that due to mutation p.G229C in the NAD(+)-binding domain. Two of the five patients presented mutations (p.D479V and p.R482G) very close to the present case (p.I480M). Despite differing degrees of clinical severity, all three had minimal clues to DLD deficiency, with occasional minor increases in α-ketoglutarate and branched-chain amino acids. In the two other patients, hypertrophic cardiomyopathy was a significant feature that has been attributed to moonlighting proteolytic activity of monomeric DLD, which can degrade other mitochondrial proteins, such as frataxin. Our patient does not have cardiomyopathy, suggesting that p.I480M may not affect the DLD ability to dimerize to the same extent as p.D479V and p.R482G. Our patient, with a novel mutation in the DLD interface and mild clinical symptoms, further broadens the spectrum of this enzyme defect.
journal_name
J Inherit Metab Disjournal_title
Journal of inherited metabolic diseaseauthors
Quintana E,Pineda M,Font A,Vilaseca MA,Tort F,Ribes A,Briones Pdoi
10.1007/s10545-010-9169-4subject
Has Abstractpub_date
2010-12-01 00:00:00pages
S315-9eissn
0141-8955issn
1573-2665journal_volume
33 Suppl 3pub_type
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
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journal_title:Journal of inherited metabolic disease
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journal_title:Journal of inherited metabolic disease
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journal_title:Journal of inherited metabolic disease
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
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journal_title:Journal of inherited metabolic disease
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
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更新日期:2017-11-01 00:00:00
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journal_title:Journal of inherited metabolic disease
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
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更新日期:2004-01-01 00:00:00
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
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journal_title:Journal of inherited metabolic disease
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1002/jimd.12244
更新日期:2020-09-01 00:00:00
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF01800730
更新日期:1983-01-01 00:00:00
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
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更新日期:2008-06-01 00:00:00
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1007/BF02179139
更新日期:1982-01-01 00:00:00
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-009-1057-4
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abstract:: ...
journal_title:Journal of inherited metabolic disease
pub_type: 社论
doi:10.1007/s10545-018-00252-y
更新日期:2018-11-01 00:00:00
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
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更新日期:2011-12-01 00:00:00
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journal_title:Journal of inherited metabolic disease
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journal_title:Journal of inherited metabolic disease
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journal_title:Journal of inherited metabolic disease
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更新日期:2010-10-01 00:00:00
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
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更新日期:2009-12-01 00:00:00
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1023/a:1005372730310
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1007/s10545-006-0269-0
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1023/a:1005669610722
更新日期:2000-09-01 00:00:00
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1007/BF01799500
更新日期:1990-01-01 00:00:00
abstract::Hawkinsinuria is a rare disorder of tyrosine metabolism that can manifest with metabolic acidosis and growth arrest around the time of weaning off breast milk, typically followed by spontaneous resolution of symptoms around 1 year of age. The urinary metabolites hawkinsin, quinolacetic acid, and pyroglutamic acid can ...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/s10545-016-9963-8
更新日期:2016-11-01 00:00:00