Pyruvate dehydrogenase lipoic acid synthetase deficiency

General Information (adopted from Orphanet):

Synonyms, Signs: PDHLD
Lipoic acid synthetase deficiency [IBIS]
Number of Symptoms 39
OrphanetNr:
OMIM Id: 614462
ICD-10:
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
[Omim]
Age of onset: Neonatal
22152680 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: No data available.

Comment:

Lipoic acid is an essential prosthetic group of four mitochondrial enzymes involved in the oxidative decarboxylation of pyruvate, alpha-ketoglutarate, and branched chain amino acids and in the glycine cleavage. It is synthesized stepwise within mitochondria through a process that includes lipoic acid synthetase. Lipoic acid synthetase deficiency is caused by mutations in the LIAS gene (= HGCLAS, HUSSY-01, LAS, LIP1, LS, PDHLD) and is the reason for symptoms like neonatal-onset epilepsy, defective mitochondrial energy metabolism, and glycine elevation.

Symptom Information: Sort by abundance 

1
(HPO:0011968) Feeding difficulties 22152680 IBIS 240 / 7739
2
(HPO:0008872) Feeding difficulties in infancy 22152680 IBIS 153 / 7739
3
(HPO:0002033) Poor suck 22152680 IBIS 37 / 7739
4
(HPO:0002113) Pulmonary infiltrates 22152680 IBIS 36 / 7739
5
(HPO:0002093) Respiratory insufficiency 22152680 IBIS 410 / 7739
6
(HPO:0011947) Respiratory tract infection 22152680 IBIS 28 / 7739
7
(HPO:0002151) Increased serum lactate 22152680 IBIS 92 / 7739
8
(HPO:0003128) Lactic acidosis 22152680 IBIS 116 / 7739
9
(HPO:0001942) Metabolic acidosis 22152680 IBIS 81 / 7739
10
(HPO:0002154) Hyperglycinemia 22152680 IBIS 12 / 7739
11
(HPO:0003150) Glutaric aciduria 22152680 IBIS 7 / 7739
12
(HPO:0001639) Hypertrophic cardiomyopathy 22152680 IBIS 137 / 7739
13
(HPO:0012087) Abnormal mitochondrial shape 22152680 IBIS 8 / 7739
14
(HPO:0011923) Decreased activity of mitochondrial complex I 22152680 IBIS 35 / 7739
15
(HPO:0008314) Decreased activity of mitochondrial complex II 22152680 IBIS 7 / 7739
16
(HPO:0011924) Decreased activity of mitochondrial complex III 22152680 IBIS 22 / 7739
17
(HPO:0002928) Decreased activity of the pyruvate dehydrogenase complex 22152680 IBIS 10 / 7739
18
(HPO:0002181) Cerebral edema 22152680 IBIS 19 / 7739
19
(HPO:0001252) Muscular hypotonia 22152680 IBIS 990 / 7739
20
(HPO:0008947) Infantile muscular hypotonia 22152680 IBIS 482 / 7739
21
(HPO:0001298) Encephalopathy 22152680 IBIS 72 / 7739
22
(HPO:0001285) Spastic tetraparesis 22152680 IBIS 29 / 7739
23
(HPO:0002510) Spastic tetraplegia 22152680 IBIS 54 / 7739
24
(HPO:0000711) Restlessness 22152680 IBIS 18 / 7739
25
(MedDRA:10003830) Automatism 22152680 IBIS 4 / 7739
26
(HPO:0011344) Severe global developmental delay 22152680 IBIS 46 / 7739
27
(HPO:0001249) Intellectual disability 22152680 IBIS 1089 / 7739
28
(HPO:0001270) Motor delay 22152680 IBIS 322 / 7739
29
(HPO:0002360) Sleep disturbance 22152680 IBIS 113 / 7739
30
(HPO:0001262) Somnolence 22152680 IBIS 20 / 7739
31
(HPO:0004372) Reduced consciousness/confusion 22152680 IBIS 73 / 7739
32
(HPO:0001250) Seizures 22152680 IBIS 1245 / 7739
33
(HPO:0000252) Microcephaly 22152680 IBIS 832 / 7739
34
(HPO:0002104) Apnea 22152680 IBIS 106 / 7739
35
(HPO:0001371) Flexion contracture 22152680 IBIS 220 / 7739
36
(HPO:0003819) Death in childhood 22152680 IBIS 42 / 7739
37
(HPO:0000238) Hydrocephalus 22152680 IBIS 278 / 7739
38
(OMIM) Biopsy shows defects in pyruvate oxidation 22152680 IBIS 1 / 7739
39
(OMIM) Decreased lipoic acid 22152680 IBIS 1 / 7739

Associated genes:

LIAS;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Pyruvate dehydrogenase lipoic acid synthetase deficiency is an autosomal recessive disorder of mitochondrial metabolism characterized by early-onset lactic acidosis, severe encephalomyopathy, and a pyruvate oxidation defect (Mayr et al., 2011).
Clinical Description OMIM Mayr et al. (2011) reported a boy, born of consanguineous Turkish parents, with a severe metabolic disorder resulting in death at age 4 years. He developed seizures on day 3 of life, and showed hypotonia and poor sucking. ...
Molecular genetics OMIM By autozygosity mapping followed by candidate gene analysis of a boy with early-onset lactic acidosis and encephalopathy, Mayr et al. (2011) identified a homozygous mutation in the LIAS gene (607031.0001).