Abstract
BackgroundDihydrolipoamide dehydrogenase deficiency (DLDD) is a rare metabolic disorder inherited in an autosomal recessive manner. This heterogeneous disease has a variable clinical presentation, onset, and biochemical markers. Materials and methodsWe retrospectively reviewed the clinical and molecular diagnosis of eight cases with DLDD from four referral centers in Saudi Arabia. ResultsRemarkably, we found hepatic involvement ranging from acute hepatic failure to chronic hepatitis in five patients. In addition, neurological disorders in the form of seizures, developmental delay, ataxia, hypotonia and psychomotor symptoms were found in five patients, two of them with a combination of hepatic and neurological symptoms. In addition, only one patient had recurrent episodes of hypoglycemia. While most patients had the hepatic form of homozygous variant c.685G > T in the DLD gene, one patient was found to have a novel variant c.623C > T that had neurological and hepatic symptoms. ConclusionsWe describe the largest reported DLDD cohort in the Saudi population. Clinical, biochemical, radiological, and molecular characterization was reviewed and no clear genotype-phenotype correlation was found in this cohort.
Highlights
Dihydrolipoamide dehydrogenase deficiency (DLDD) is an extremely rare metabolic disorder with autosomal recessive inheritance [1]
DLDD is caused by a deficiency of the enzyme the dihydrolipoamide dehydrogenase, which is encoded by the DLD gene in 7q31.1 [4]
We retrospectively reviewed the clinical and molecular diagnosis of 8 cases with a confirmed diagnosis of DLDD from four participating centers in Saudi Arabia to describe the phenotypic spectrum of this rare disease, which may help to establish a consensus on a treatment protocol for such cases in the future
Summary
Dihydrolipoamide dehydrogenase deficiency (DLDD) is an extremely rare metabolic disorder with autosomal recessive inheritance [1]. DLDD is caused by a deficiency of the enzyme the dihydrolipoamide dehydrogenase, which is encoded by the DLD gene in 7q31.1 [4] This enzyme, a flavoprotein unit designated E3, is one of three mitochondrial multi-enzymatic complexes, which include a pyruvate dehydrogenase complex, an a-ketoglutarate dehydrogenase complex, and a branchedchain a-keto acid complex, and plays a role in the glycine cleavage system. Dihydrolipoamide dehydrogenase deficiency (DLDD) is a rare metabolic disorder inherited in an autosomal recessive manner. This heterogeneous disease has a variable clinical presentation, onset, and biochemical markers. Biochemical, radiological, and molecular characterization was reviewed and no clear genotype-phenotype correlation was found in this cohort
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