IllnessPyruvatdehydrogenase deficiency, differential diagnosis

Summary

Short information

Comprehensive differential diagnostic panel for Pyruvat dehydrogenase deficiency containing 1 guideline-curated core gene, 23 core candidate genes and altogether 28 curated genes according to the clinical signs

PP2231

Number of genes

24 Accredited laboratory test

Examined sequence length

27,5 kb (Core-/Core-canditate-Genes)
- (Extended panel: incl. additional genes)

Analysis Duration

on request

Material

EDTA-anticoagulated blood (3-5 ml)

Diagnostic indications

NGS +

Gene panel

Selected genes

Name	Exon Length (bp)	OMIM-G	Referenz-Seq.	Heredity
BOLA3	324	613183	NM_212552.3	AR
DLAT	1944	608770	NM_001931.5	AR
DLD	1530	238331	NM_000108.5	AR
ECHS1	873	602292	NM_004092.4	AR
FBXL4	1866	605654	NM_012160.5	AR
GLRX5	474	609588	NM_016417.3	AR
HIBCH	1161	610690	NM_014362.4	AR
IBA57	1071	615316	NM_001010867.4	AR
ISCA1	415	611006	NM_030940.4	AR
ISCA2	183	615317	NM_194279.4	AR
LIAS	990	607031	NM_001278590.2	AR
LIPT1	1122	610284	NM_001204830.2	AR
LIPT2	982	617659	NM_001144869.3	AR
LONP1	2688	605490	NM_001276479.2	AR
NFU1	765	608100	NM_001002755.4	AR
PDHA1	1173	300502	NM_000284.4	XL
PDHB	1080	179060	NM_000925.4	AR
PDHX	1506	608769	NM_003477.3	AR
PDP1	1689	605993	NM_001161779.2	AR
SLC19A2	1494	603941	NM_006996.3	AR
SLC19A3	1491	606152	NM_025243.4	AR
SLC25A19	963	606521	NM_001126121.2	AR
SLC25A26	1100	611037	NM_001164796.1	AR
TPK1	585	606370	NM_001042482.2	AR

Informations about the disease

Clinical Comment

Rare neurometabolic disorder, wide range of clinical signs, metabolic + neurological components, varying severity; often fatal neonatal lactic acidosis or later-onset neurological disorders; 6 subtypes related to affected subunit of PDH complex, significant clinical overlap: PDHD due to E1-alpha, E1-beta, E2 and E3 deficiency, PDHD due to E3-binding protein deficiency, PDH phosphatase deficiency

Synonyms

Alias: Ahornsirup-Krankheit, E3-defiziente (DLD)
Alias: Dihydro-Lipoamid-Dehydrogenase-Mangel (DLD)
Alias: Dihydrolipoamide dehydrogenase deficiency (DLD)
3-hydroxyisobutryl-CoA hydrolase deficiency (HIBCH)
Anemia, sideroblastic, 3, pyridoxine-refractory (GLRX5)
CODAS (cerebral, ocular, dental, auricular, skeletal anomalies) syndrome (LONP1)
Charcot-Marie-Tooth disease, XLD, 6 (PDK3)
Combined D-2- + L-2-hydroxyglutaric aciduria (SLC25A1)
Combined oxidative phosphorylation deficiency 28 (SLC25A26)
Encephalopathy, neonatal severe, with lactic acidosis + brain abnormalities (LIPT2)
HARP syndrome (PANK2)
Hyperglycinemia, lactic acidosis + seizures (LIAS)
Lacticacidemia due to PDX1 deficiency (PDHX)
Lipoyltransferase 1 deficiency (LIPT1)
Microcephaly, Amish type (SLC24A19)
Mitochondrial DNA depletion syndrome, encephalomyopathic type (FBXL4)
Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency (ECHS1)
Multiple mitochondrial dysfunctions syndrome 1 (NFU1)
Multiple mitochondrial dysfunctions syndrome 3 (IBA57)
Multiple mitochondrial dysfunctions syndrome 4 (ISCA2)
Multiple mitochondrial dysfunctions syndrome 5 (ISCA1)
Multiple mitochondrial dysfunctions syndrome 6 (PMPCB)
Multiple mitochondrial dysfunctions syndrome with hyperglycinemia (BOLA3)
Myasthenic syndrome, congenital, 23, presynaptic (SLC25A1)
Neurodegeneration with brain iron accumulation 1 (PANK2)
Pyruvate dehydrogenase E1-alpha deficiency (PDHA1)
Pyruvate dehydrogenase E1-beta deficiency (PDHB)
Pyruvate dehydrogenase E2 deficiency (DLAT)
Pyruvate dehydrogenase phosphatase deficiency (PDP1)
Spasticity, childhood-onset, with hyperglycinemia (GLRX5)
Thiamine metabolism dysfunction syndrome 4, progressive polyneuropathy type (SLC25A19)
Thiamine metabolism dysfunction syndrome 5, episodic encephalopathy type (TPK1)
Thiamine metabolism dysfunction syndrome, biotin/thiamine-responsive encephalopathy type2 (SLC19A3)
Thiamine-responsive megaloblastic anemia syndrome (SLC19A2)

Heredity, heredity patterns etc.

OMIM-Ps

Multiple OMIM-Ps

ICD10 Code

Bioinformatics and clinical interpretation

No text defined