MCID: HYP719
MIFTS: 22

Hyperglycinemia, Lactic Acidosis, and Seizures

Categories: Genetic diseases, Neuronal diseases, Metabolic diseases, Rare diseases

Aliases & Classifications for Hyperglycinemia, Lactic Acidosis, and Seizures

MalaCards integrated aliases for Hyperglycinemia, Lactic Acidosis, and Seizures:

Name: Hyperglycinemia, Lactic Acidosis, and Seizures 57 75
Pyruvate Dehydrogenase Lipoic Acid Synthetase Deficiency 57 75 29 13 6 40 73
Hgclas 57 75
Pdhld 57 75
Pyruvate Dehydrogenase Lipoic Acid Synthetase Deficiency; Pdhld 57
Lipoic Acid Synthetase Deficiency 59

Characteristics:

Orphanet epidemiological data:

59
lipoic acid synthetase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Neonatal; Age of death: early childhood;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
severe disorder
onset in first days of life
metabolic decompensation, episodic
four patients from 3 families have been reported (last curated march 2016)


HPO:

32
hyperglycinemia, lactic acidosis, and seizures:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Hyperglycinemia, Lactic Acidosis, and Seizures

OMIM : 57 Hyperglycinemia, lactic acidosis, and seizures is a severe autosomal recessive disorder characterized by onset of hypotonia and seizures associated with increased serum glycine and lactate in the first days of life. Affected individuals develop an encephalopathy or severely delayed psychomotor development, which may result in death in childhood. The disorder represents a form of 'variant' nonketotic hyperglycinemia and is distinct from classic nonketotic hyperglycinemia (NKH, or GCE; 605899), which is characterized by significantly increased CSF glycine. Several forms of 'variant' NKH, including HGCLAS, appear to result from defects of mitochondrial lipoate biosynthesis (summary by Baker et al., 2014). (614462)

MalaCards based summary : Hyperglycinemia, Lactic Acidosis, and Seizures, also known as pyruvate dehydrogenase lipoic acid synthetase deficiency, is related to lipoic acid synthetase deficiency, and has symptoms including apnea, myoclonus and seizures. An important gene associated with Hyperglycinemia, Lactic Acidosis, and Seizures is LIAS (Lipoic Acid Synthetase). Related phenotypes are microcephaly and seizures

UniProtKB/Swiss-Prot : 75 Hyperglycinemia, lactic acidosis, and seizures: An enzymatic defect resulting in an autosomal recessive disorder of mitochondrial metabolism. It is characterized by early-onset lactic acidosis, severe encephalomyopathy, and a pyruvate oxidation defect. Affected individuals have neonatal-onset epilepsy, poor growth, psychomotor retardation, muscular hypotonia, lactic acidosis, and elevated glycine concentration in plasma and urine.

Related Diseases for Hyperglycinemia, Lactic Acidosis, and Seizures

Diseases related to Hyperglycinemia, Lactic Acidosis, and Seizures via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 lipoic acid synthetase deficiency 11.7

Symptoms & Phenotypes for Hyperglycinemia, Lactic Acidosis, and Seizures

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
seizures
spastic tetraplegia
myoclonus
sleep disturbances
encephalopathy, episodic
more
Head And Neck Head:
microcephaly

Metabolic Features:
lactic acidosis

Growth Other:
poor feeding
poor growth

Cardiovascular Heart:
hypertrophic cardiomyopathy (in some patients)

Respiratory:
respiratory insufficiency
apnea

Laboratory Abnormalities:
increased serum lactate
decreased activity of the pyruvate dehydrogenase (pdh) complex
increased urinary and serum glycine
increased urinary glutaric acid
decreased activity of the glycine cleavage enzyme system

Muscle Soft Tissue:
hypotonia
enlarged mitochondria
biopsy shows defects in pyruvate oxidation
decreased lipoic acid

Skeletal:
contractures


Clinical features from OMIM:

614462

Human phenotypes related to Hyperglycinemia, Lactic Acidosis, and Seizures:

32 (show all 20)
# Description HPO Frequency HPO Source Accession
1 microcephaly 32 HP:0000252
2 seizures 32 HP:0001250
3 motor delay 32 HP:0001270
4 generalized hypotonia 32 HP:0001290
5 encephalopathy 32 HP:0001298
6 myoclonus 32 HP:0001336
7 flexion contracture 32 HP:0001371
8 growth delay 32 HP:0001510
9 hypertrophic cardiomyopathy 32 HP:0001639
10 cerebral atrophy 32 occasional (7.5%) HP:0002059
11 respiratory insufficiency 32 HP:0002093
12 apnea 32 HP:0002104
13 increased serum lactate 32 HP:0002151
14 sleep disturbance 32 HP:0002360
15 leukodystrophy 32 occasional (7.5%) HP:0002415
16 spastic tetraplegia 32 HP:0002510
17 lactic acidosis 32 HP:0003128
18 severe global developmental delay 32 HP:0011344
19 feeding difficulties 32 HP:0011968
20 profound global developmental delay 32 HP:0012736

UMLS symptoms related to Hyperglycinemia, Lactic Acidosis, and Seizures:


apnea, myoclonus, seizures, sleep disturbances

Drugs & Therapeutics for Hyperglycinemia, Lactic Acidosis, and Seizures

Search Clinical Trials , NIH Clinical Center for Hyperglycinemia, Lactic Acidosis, and Seizures

Genetic Tests for Hyperglycinemia, Lactic Acidosis, and Seizures

Genetic tests related to Hyperglycinemia, Lactic Acidosis, and Seizures:

# Genetic test Affiliating Genes
1 Pyruvate Dehydrogenase Lipoic Acid Synthetase Deficiency 29 LIAS

Anatomical Context for Hyperglycinemia, Lactic Acidosis, and Seizures

Publications for Hyperglycinemia, Lactic Acidosis, and Seizures

Articles related to Hyperglycinemia, Lactic Acidosis, and Seizures:

# Title Authors Year
1
Lipoic acid synthetase deficiency causes neonatal-onset epilepsy, defective mitochondrial energy metabolism, and glycine elevation. ( 22152680 )
2011

Variations for Hyperglycinemia, Lactic Acidosis, and Seizures

UniProtKB/Swiss-Prot genetic disease variations for Hyperglycinemia, Lactic Acidosis, and Seizures:

75
# Symbol AA change Variation ID SNP ID
1 LIAS p.Arg249His VAR_067839 rs144133667

ClinVar genetic disease variations for Hyperglycinemia, Lactic Acidosis, and Seizures:

6
(show top 50) (show all 60)
# Gene Variation Type Significance SNP ID Assembly Location
1 LIAS NM_006859.3(LIAS): c.746G> A (p.Arg249His) single nucleotide variant Pathogenic rs144133667 GRCh37 Chromosome 4, 39471647: 39471647
2 LIAS NM_006859.3(LIAS): c.746G> A (p.Arg249His) single nucleotide variant Pathogenic rs144133667 GRCh38 Chromosome 4, 39470027: 39470027
3 LIAS NM_006859.3(LIAS): c.31A> T (p.Thr11Ser) single nucleotide variant Likely benign rs147516123 GRCh37 Chromosome 4, 39460768: 39460768
4 LIAS NM_006859.3(LIAS): c.31A> T (p.Thr11Ser) single nucleotide variant Likely benign rs147516123 GRCh38 Chromosome 4, 39459148: 39459148
5 LIAS NM_006859.3(LIAS): c.122A> G (p.Asn41Ser) single nucleotide variant Uncertain significance rs761295906 GRCh37 Chromosome 4, 39462486: 39462486
6 LIAS NM_006859.3(LIAS): c.122A> G (p.Asn41Ser) single nucleotide variant Uncertain significance rs761295906 GRCh38 Chromosome 4, 39460866: 39460866
7 LIAS NM_006859.3(LIAS): c.393+8C> A single nucleotide variant Benign rs201574806 GRCh37 Chromosome 4, 39465233: 39465233
8 LIAS NM_006859.3(LIAS): c.393+8C> A single nucleotide variant Benign rs201574806 GRCh38 Chromosome 4, 39463613: 39463613
9 LIAS NM_006859.3(LIAS): c.849C> T (p.Gly283=) single nucleotide variant Conflicting interpretations of pathogenicity rs146030265 GRCh37 Chromosome 4, 39471750: 39471750
10 LIAS NM_006859.3(LIAS): c.849C> T (p.Gly283=) single nucleotide variant Conflicting interpretations of pathogenicity rs146030265 GRCh38 Chromosome 4, 39470130: 39470130
11 LIAS NM_006859.3(LIAS): c.944G> A (p.Arg315His) single nucleotide variant Uncertain significance rs145535775 GRCh37 Chromosome 4, 39472916: 39472916
12 LIAS NM_006859.3(LIAS): c.944G> A (p.Arg315His) single nucleotide variant Uncertain significance rs145535775 GRCh38 Chromosome 4, 39471296: 39471296
13 LIAS NM_006859.3(LIAS): c.475_477delGAGinsAAA (p.Glu159Lys) indel Pathogenic rs869320760 GRCh37 Chromosome 4, 39466747: 39466749
14 LIAS NM_006859.3(LIAS): c.475_477delGAGinsAAA (p.Glu159Lys) indel Pathogenic rs869320760 GRCh38 Chromosome 4, 39465127: 39465129
15 LIAS NM_006859.3(LIAS): c.645T> A (p.Asp215Glu) single nucleotide variant Pathogenic rs869312808 GRCh38 Chromosome 4, 39467554: 39467554
16 LIAS NM_006859.3(LIAS): c.645T> A (p.Asp215Glu) single nucleotide variant Pathogenic rs869312808 GRCh37 Chromosome 4, 39469174: 39469174
17 LIAS NM_006859.3(LIAS): c.57A> C (p.Arg19Ser) single nucleotide variant Benign rs140921822 GRCh38 Chromosome 4, 39460801: 39460801
18 LIAS NM_006859.3(LIAS): c.57A> C (p.Arg19Ser) single nucleotide variant Benign rs140921822 GRCh37 Chromosome 4, 39462421: 39462421
19 LIAS NM_006859.3(LIAS): c.393+4G> A single nucleotide variant Conflicting interpretations of pathogenicity rs368453789 GRCh37 Chromosome 4, 39465229: 39465229
20 LIAS NM_006859.3(LIAS): c.393+4G> A single nucleotide variant Conflicting interpretations of pathogenicity rs368453789 GRCh38 Chromosome 4, 39463609: 39463609
21 LIAS NM_006859.3(LIAS): c.60T> C (p.Tyr20=) single nucleotide variant Likely benign rs201996792 GRCh38 Chromosome 4, 39460804: 39460804
22 LIAS NM_006859.3(LIAS): c.60T> C (p.Tyr20=) single nucleotide variant Likely benign rs201996792 GRCh37 Chromosome 4, 39462424: 39462424
23 LIAS NM_006859.3(LIAS): c.114C> A (p.Leu38=) single nucleotide variant Likely benign rs750439302 GRCh37 Chromosome 4, 39462478: 39462478
24 LIAS NM_006859.3(LIAS): c.114C> A (p.Leu38=) single nucleotide variant Likely benign rs750439302 GRCh38 Chromosome 4, 39460858: 39460858
25 LIAS NM_006859.3(LIAS): c.726G> A (p.Pro242=) single nucleotide variant Benign rs371053949 GRCh37 Chromosome 4, 39469255: 39469255
26 LIAS NM_006859.3(LIAS): c.726G> A (p.Pro242=) single nucleotide variant Benign rs371053949 GRCh38 Chromosome 4, 39467635: 39467635
27 LIAS NM_006859.3(LIAS): c.120G> T (p.Gln40His) single nucleotide variant Uncertain significance rs1041843537 GRCh38 Chromosome 4, 39460864: 39460864
28 LIAS NM_006859.3(LIAS): c.120G> T (p.Gln40His) single nucleotide variant Uncertain significance rs1041843537 GRCh37 Chromosome 4, 39462484: 39462484
29 LIAS NM_006859.3(LIAS): c.737+9G> A single nucleotide variant Likely benign rs750744754 GRCh38 Chromosome 4, 39467655: 39467655
30 LIAS NM_006859.3(LIAS): c.737+9G> A single nucleotide variant Likely benign rs750744754 GRCh37 Chromosome 4, 39469275: 39469275
31 LIAS NM_006859.3(LIAS): c.7C> T (p.Leu3=) single nucleotide variant Likely benign GRCh38 Chromosome 4, 39459124: 39459124
32 LIAS NM_006859.3(LIAS): c.7C> T (p.Leu3=) single nucleotide variant Likely benign GRCh37 Chromosome 4, 39460744: 39460744
33 LIAS NM_006859.3(LIAS): c.218G> C (p.Arg73Thr) single nucleotide variant Uncertain significance GRCh38 Chromosome 4, 39460962: 39460962
34 LIAS NM_006859.3(LIAS): c.218G> C (p.Arg73Thr) single nucleotide variant Uncertain significance GRCh37 Chromosome 4, 39462582: 39462582
35 LIAS NC_000004.12: g.(?_39459098)_(39477135_?)dup duplication Uncertain significance GRCh38 Chromosome 4, 39459098: 39477135
36 LIAS NC_000004.12: g.(?_39459098)_(39477135_?)dup duplication Uncertain significance GRCh37 Chromosome 4, 39460718: 39478755
37 LIAS NM_006859.3(LIAS): c.529C> T (p.Leu177=) single nucleotide variant Likely benign rs750168413 GRCh38 Chromosome 4, 39465181: 39465181
38 LIAS NM_006859.3(LIAS): c.529C> T (p.Leu177=) single nucleotide variant Likely benign rs750168413 GRCh37 Chromosome 4, 39466801: 39466801
39 LIAS NM_006859.3(LIAS): c.110A> T (p.Glu37Val) single nucleotide variant Uncertain significance rs763606110 GRCh37 Chromosome 4, 39462474: 39462474
40 LIAS NM_006859.3(LIAS): c.110A> T (p.Glu37Val) single nucleotide variant Uncertain significance rs763606110 GRCh38 Chromosome 4, 39460854: 39460854
41 LIAS NM_006859.3(LIAS): c.363delA (p.Glu122Asnfs) deletion Pathogenic GRCh37 Chromosome 4, 39465195: 39465195
42 LIAS NM_006859.3(LIAS): c.363delA (p.Glu122Asnfs) deletion Pathogenic GRCh38 Chromosome 4, 39463575: 39463575
43 LIAS NM_006859.3(LIAS): c.129A> G (p.Pro43=) single nucleotide variant Likely benign rs377315137 GRCh37 Chromosome 4, 39462493: 39462493
44 LIAS NM_006859.3(LIAS): c.129A> G (p.Pro43=) single nucleotide variant Likely benign rs377315137 GRCh38 Chromosome 4, 39460873: 39460873
45 LIAS NM_006859.3(LIAS): c.173C> T (p.Thr58Ile) single nucleotide variant Uncertain significance rs141723499 GRCh37 Chromosome 4, 39462537: 39462537
46 LIAS NM_006859.3(LIAS): c.173C> T (p.Thr58Ile) single nucleotide variant Uncertain significance rs141723499 GRCh38 Chromosome 4, 39460917: 39460917
47 LIAS NM_006859.3(LIAS): c.473G> C (p.Ser158Thr) single nucleotide variant Uncertain significance rs751421705 GRCh37 Chromosome 4, 39466745: 39466745
48 LIAS NM_006859.3(LIAS): c.473G> C (p.Ser158Thr) single nucleotide variant Uncertain significance rs751421705 GRCh38 Chromosome 4, 39465125: 39465125
49 LIAS NM_006859.3(LIAS): c.553_561delATGCCTGAT (p.Met185_Asp187del) deletion Uncertain significance GRCh38 Chromosome 4, 39465287: 39465295
50 LIAS NM_006859.3(LIAS): c.553_561delATGCCTGAT (p.Met185_Asp187del) deletion Uncertain significance GRCh37 Chromosome 4, 39466907: 39466915

Expression for Hyperglycinemia, Lactic Acidosis, and Seizures

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Pathways for Hyperglycinemia, Lactic Acidosis, and Seizures

GO Terms for Hyperglycinemia, Lactic Acidosis, and Seizures

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