Disorders assoc w/secondary PDCD that are phenotypically similar to primary PDCD
|
BOLA3
IBA57
ISCA1
ISCA2
NFU1
PMPCB
| Multiple mitochondrial dysfunction syndromes (OMIM PS605711) | AR | Leigh syndrome, seizures, spasticity, & mvmt disorder; unlike primary PDCD, MMDS is assoc w/optic atrophy, cardiomyopathy, leukodystrophy. | Neonatal lactic acidosis; ↓ PDC enzyme activity in at least fibroblasts & skeletal muscle cells for some; unlike primary PDCD, MMDS is assoc w/↑ glycine & electron transport chain enzyme activity deficiencies. |
ECHS1
| Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency (ECHS1D) | AR | Leigh syndrome, long philtrum, & episodic dystonia; may be a complete phenocopy of primary PDCD 1; corpus callosum dysgenesis/agenesis | Lactic acidosis & & ↑ pyruvate (lactate:pyruvate ratio may be nl); unlike primary PDCD, ECHS1D may be assoc w/abnl acylcarnitine profile or ↑urine organic acid w/marked 2-methyl-2,3-dihydroxybutyric acid. |
HIBCH
| 3-hydroxyisobutyryl-CoA hydrolase deficiency (HIBCHD) (OMIM 250620) | AR | Leigh syndrome & long philtrum; corpus callosum dysgenesis/agenesis | Lactic acidosis & ↑ pyruvate (lactate:pyruvate ratio may be nl); unlike primary PDCD, HIBCHD may be assoc w/abnl acylcarnitine profile or urine organic acids. |
LIAS
| Hyperglycinemia, lactic acidosis, and seizures (OMIM 614462) | AR | Epileptic encephalopathy, lactic acidosis | Lactic acidosis & ↑ pyruvate (lactate:pyruvate ratio may be nl or ↑); ↓ PDC enzyme activity (muscle, fibroblasts); unlike primary PDCD, lipoic acid synthesis defects are assoc w/↑ glycine & electron transport chain enzyme activity deficiencies. |
LIPT1
| Lipoyltransferase 1 deficiency (LIPT1D; OMIM 616299) |
LIPT2
| Lipoyltransferase 2 deficiency (OMIM 617668) |
SLC25A1
| Mitochondrial citrate carrier deficiency (combined D-2- & L-2-hydroxyglutaric aciduria; OMIM 615182) | AR | Unlike primary PDCD, MCCD is assoc w/facial dysmorphism & apnea; intracerebral cysts. | Neonatal lactic acidosis & ↑ 2-hydroxyglutaric acid |
TPK1
| Thiamine pyrophosphokinase deficiency (thiamine metabolism dysfunction syndrome 5 - episodic encephalopathy type; OMIM 614458) | AR | Developmental regression, ataxia, dystonia, & microcephaly; typically higher developmental achievement than in PDCD. | ↑ lactate & ↑ pyruvate; nl lactate:pyruvate ratio. Note: Treatable w/high dose thiamine 2 |
Other disorders (not assoc w/inhibition of PDCs) that are phenotypically similar to primary PDCD
|
~90 genes | Other Leigh syndromes (See Nuclear Gene-Encoded Leigh Syndrome Overview & mtDNA-Associated Leigh Syndrome & NARP.) | AR AD XL Mat | Dystonia & developmental regression; T2-weighted hyperintensity of the basal ganglia | Lactic acidosis. Note: Electron transport chain defects typically → nl pyruvate. If pyruvate is ↑, lactate:pyruvate ratio is > nl (>20) due to dysfunction of electron transport chain. |
FBXL4
|
FBXL4-related encephalomyopathic mtDNA depletion syndrome
| AR | Leigh syndrome & long philtrum; corpus callosum dysgenesis/agenesis | Lactic acidosis & ↑ pyruvate; hyperammonemia may be more striking than in primary PDCD. |
PANK2
| Pantothenate kinase-associated neurodegeneration (PKAN) | AR | Dystonia, spasticity, dysarthria, intellectual impairment; "eye of the tiger" MRI sign (classic for PKAN) is absent in primary PDCD (Globus pallidus lesions in DLAT-PDCD resemble PKAN but DLAT-PDCD is not assoc w/eye of the tiger MRI sign.) | Unlike primary PDCD, PKAN is assoc w/acanthocytosis & low/absent plasma pre-beta lipoprotein fraction. |