Dihydrolipoamide dehydrogenase (DLD) deficiency in a Spanish patient with myopathic presentation due to a new mutation in the interface domain

Journal of Inherited Metabolic Disease
Ester QuintanaPaz Briones

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 increas...Continue Reading

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Citations

Jan 8, 2013·Pediatric Neurology·Shane C QuinonezJirair K Bedoyan
Mar 6, 2012·Journal of the Neurological Sciences·Khanh vinh quôc Lu'o'ng, Lan Thi Hoàng Nguyên
Jun 24, 2016·Clinical and Translational Gastroenterology·Antonio F Di NarzoKe Hao
Dec 21, 2014·Journal of Inherited Metabolic Disease·Wolfgang SperlJohannes A Mayr

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