The phenotypic spectrum of dihydrolipoamide dehydrogenase deficiency in Saudi Arabia.
BCAAs, Branched Chain Amino Acids
BCKDH, Branched-chain a-keto acid dehydrogenase
DCA, Dichloroacetate
DLDD, Dihydrolipoamide Dehydrogenase Deficiency
Dihydrolipoamide dehydrogenase deficiency
Flavoprotein and E3
Hypoglycemia
IRB, Institutional Review Board
KAIMRC, King Abdullah International Medical Research Centre
Lactic acidosis
MRI, Magnetic resonance imaging
PDH, Pyruvate dehydrogenase
Pyruvate dehydrogenase complex
WES, Whole Exome Sequencing
αKGDH, alpha-ketoglutarate dehydrogenase
Journal
Molecular genetics and metabolism reports
ISSN: 2214-4269
Titre abrégé: Mol Genet Metab Rep
Pays: United States
ID NLM: 101624422
Informations de publication
Date de publication:
Dec 2021
Dec 2021
Historique:
received:
13
09
2021
revised:
18
10
2021
accepted:
19
10
2021
entrez:
8
11
2021
pubmed:
9
11
2021
medline:
9
11
2021
Statut:
epublish
Résumé
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. We retrospectively reviewed the clinical and molecular diagnosis of eight cases with DLDD from four referral centers in Saudi Arabia. Remarkably, 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 We 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.
Sections du résumé
BACKGROUND
BACKGROUND
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.
MATERIALS AND METHODS
METHODS
We retrospectively reviewed the clinical and molecular diagnosis of eight cases with DLDD from four referral centers in Saudi Arabia.
RESULTS
RESULTS
Remarkably, 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
CONCLUSIONS
CONCLUSIONS
We 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.
Identifiants
pubmed: 34745891
doi: 10.1016/j.ymgmr.2021.100817
pii: S2214-4269(21)00112-9
pmc: PMC8554626
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100817Informations de copyright
© 2021 The Authors.
Déclaration de conflit d'intérêts
The authors declare that they have no competing financial interests.
Références
Proc Natl Acad Sci U S A. 1988 Mar;85(5):1422-6
pubmed: 3278312
Mitochondrion. 2014 Sep;18:49-57
pubmed: 25251739
Pediatr Neurol. 2013 Jan;48(1):67-72
pubmed: 23290025
J Pediatr Gastroenterol Nutr. 1997 May;24(5):599-601
pubmed: 9161958
J Inherit Metab Dis. 2003;26(8):816-8
pubmed: 14765544
J Inherit Metab Dis. 2006 Feb;29(1):203-4
pubmed: 16601893
Am J Med Genet A. 2006 Jul 15;140(14):1542-52
pubmed: 16770810
Eur J Pediatr. 2014 Feb;173(2):243-5
pubmed: 23995961
Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5186-90
pubmed: 8506365
Hum Mutat. 2010 Nov;31(11):1240-50
pubmed: 20672374
Biochem Biophys Res Commun. 1999 Aug 19;262(1):163-6
pubmed: 10448086
Mol Genet Metab. 2013 May;109(1):28-32
pubmed: 23478190
Orphanet J Rare Dis. 2020 Oct 22;15(1):298
pubmed: 33092611
Neurochem Int. 2007 Jun;50(7-8):921-31
pubmed: 17482317
J Pediatr. 1984 Jan;104(1):65-9
pubmed: 6418873
J Biol Chem. 2014 May 30;289(22):15215-30
pubmed: 24742683
Hum Mol Genet. 1996 Dec;5(12):1925-30
pubmed: 8968745
Biochim Biophys Acta. 1997 Dec 31;1362(2-3):160-8
pubmed: 9540846
Hum Mutat. 2005 Mar;25(3):323-4
pubmed: 15712224
Am J Med Genet. 1999 Jan 15;82(2):177-82
pubmed: 9934985
Pediatr Res. 1977 Dec;11(12):1198-202
pubmed: 413089
J Pediatr. 1995 Jan;126(1):72-4
pubmed: 7815230
Mol Genet Metab Rep. 2014 Aug 15;1:345-349
pubmed: 27896107