MCID: GLY014
MIFTS: 48

Glycerol Kinase Deficiency

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

Aliases & Classifications for Glycerol Kinase Deficiency

MalaCards integrated aliases for Glycerol Kinase Deficiency:

Name: Glycerol Kinase Deficiency 57 12 53 75 37 13 55 15
Hyperglycerolemia 57 76 53 59 75
Deficiency of Glycerol Kinase 29 6 73
Gk1 Deficiency 57 53 75
Gk Deficiency 57 53 75
Gkd 57 53 75
Glycerol Kinase Deficiency, Infantile Form 59
Glycerol Kinase Deficiency, Juvenile Form 59
Glycerol Kinase Deficiency, Adult Form 59
Isolated Glycerol Kinase Deficiency 59
Deficiency, Glycerol Kinase 40
Glycerol Kinase 13

Characteristics:

Orphanet epidemiological data:

59
isolated glycerol kinase deficiency
Inheritance: X-linked recessive; Age of onset: All ages;

OMIM:

57
Miscellaneous:
variable clinical phenotype
infantile form (gene deletion 'complex' with glycerol kinase deficiency and/or duchenne muscular dystrophy and/or congenital adrenal hypoplasia)
juvenile and adult forms are isolated glycerol kinase deficiency
adult form is asymptomatic

Inheritance:
x-linked recessive



Classifications:



Summaries for Glycerol Kinase Deficiency

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 408Disease definitionIsolated glycerol kinase deficiency (GKD) is a very rare X-linked disorder of glycerol metabolism characterized biochemically by elevated plasma and urine glycerol levels, and clinically by variable neurometabolic manifestations, depending on the age of onset, and varying from a life-threatening childhood metabolic crisis to an asymptomatic adult form (infantile GKD, juvenile GKD, and adult GKD (see these terms)).Visit the Orphanet disease page for more resources.

MalaCards based summary : Glycerol Kinase Deficiency, also known as hyperglycerolemia, is related to chromosome xp21 deletion syndrome and adrenal hypoplasia, congenital, and has symptoms including seizures An important gene associated with Glycerol Kinase Deficiency is GK (Glycerol Kinase), and among its related pathways/superpathways are Glycerolipid metabolism and PPAR signaling pathway. Affiliated tissues include eye, liver and skeletal muscle, and related phenotypes are intellectual disability and seizures

Disease Ontology : 12 An inherited metabolic disorder characterized_by wide range of phenotypic variability; patients can have severe metabolic and CNS abnormalities, while others possess hyperglycerolemia and glyceroluria with no other apparent phenotype. It has material basis in mutation in the GK gene on chromosome Xp21.

OMIM : 57 Francke et al. (1987) noted that there are 3 clinically distinct forms of glycerol kinase deficiency: infantile, juvenile, and adult. The infantile form is associated with severe developmental delay, and those with the adult form have no symptoms and are often detected fortuitously. The infantile form of GK deficiency, or the 'GK complex,' results from the Xp21 contiguous gene deletion syndrome (300679) with congenital adrenal hypoplasia (300200) and/or Duchenne muscular dystrophy (DMD; 310200), whereas the juvenile and adult forms have isolated GK deficiency (Walker et al., 1996). (307030)

UniProtKB/Swiss-Prot : 75 Glycerol kinase deficiency: A metabolic disorder manifesting as 3 clinically distinct forms: infantile, juvenile, and adult. The infantile form is the most severe and is associated with severe developmental delay and adrenal insufficiency. Patients with the adult form have no symptoms and are often detected fortuitously. GKD results in hyperglycerolemia, a condition characterized by the accumulation of glycerol in the blood and urine.

Wikipedia : 76 Hyperglycerolemia, also known as Glycerol kinase deficiency (GKD), is a genetic disorder where the... more...

Related Diseases for Glycerol Kinase Deficiency

Graphical network of the top 20 diseases related to Glycerol Kinase Deficiency:



Diseases related to Glycerol Kinase Deficiency

Symptoms & Phenotypes for Glycerol Kinase Deficiency

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
hypertelorism
strabismus
rounded palpebral fissures

Head And Neck Face:
frontal bossing
mild facial dysmorphism may occur
'hourglass' midface

Growth Height:
short stature

Laboratory Abnormalities:
hypoglycemia
increased urinary glycerol
increased serum glycerol
decreased glycerol kinase activity
pseudohypertriglyceridemia in adult form

Growth Other:
small for gestational age

GenitourinaryInternal GenitaliaMale:
cryptorchidism may occur

Endocrine Features:
adrenal insufficiency, congenital in 'complex' form

Head And Neck Ears:
low-set ears
wide, flattened earlobes

Neurologic Central Nervous System:
seizures
psychomotor retardation
mental retardation may occur

Skeletal:
osteoporosis

Metabolic Features:
metabolic acidosis
ketoacidosis
lethargy or loss of consciousness during illness or fasting

Head And Neck Mouth:
downturned mouth

Muscle Soft Tissue:
duchenne muscular dystrophy (dmd, ) in 'complex' form


Clinical features from OMIM:

307030

Human phenotypes related to Glycerol Kinase Deficiency:

59 32 (show all 35)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 59 32 hallmark (90%) Very frequent (99-80%) HP:0001249
2 seizures 59 32 frequent (33%) Frequent (79-30%) HP:0001250
3 muscular hypotonia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001252
4 neurological speech impairment 59 32 hallmark (90%) Very frequent (99-80%) HP:0002167
5 eeg abnormality 59 32 frequent (33%) Frequent (79-30%) HP:0002353
6 scoliosis 59 32 frequent (33%) Frequent (79-30%) HP:0002650
7 hyperlordosis 59 32 frequent (33%) Frequent (79-30%) HP:0003307
8 global developmental delay 59 32 hallmark (90%) Very frequent (99-80%) HP:0001263
9 short stature 59 32 hallmark (90%) Very frequent (99-80%) HP:0004322
10 myopathy 59 32 hallmark (90%) Very frequent (99-80%) HP:0003198
11 osteoporosis 59 32 frequent (33%) Frequent (79-30%) HP:0000939
12 elevated serum creatine phosphokinase 59 32 hallmark (90%) Very frequent (99-80%) HP:0003236
13 emg abnormality 59 32 hallmark (90%) Very frequent (99-80%) HP:0003457
14 cryptorchidism 59 32 occasional (7.5%) Frequent (79-30%) HP:0000028
15 reduced tendon reflexes 59 32 hallmark (90%) Very frequent (99-80%) HP:0001315
16 metabolic acidosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0001942
17 adrenocortical hypoplasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0008182
18 hypertelorism 32 HP:0000316
19 low-set ears 32 HP:0000369
20 frontal bossing 32 HP:0002007
21 abnormal facial shape 32 occasional (7.5%) HP:0001999
22 hypoglycemia 32 HP:0001943
23 hypertriglyceridemia 32 HP:0002155
24 strabismus 32 HP:0000486
25 pathologic fracture 32 HP:0002756
26 growth delay 32 HP:0001510
27 downturned corners of mouth 32 HP:0002714
28 coma 32 HP:0001259
29 lethargy 32 HP:0001254
30 muscular dystrophy 32 HP:0003560
31 adrenal insufficiency 32 HP:0000846
32 small for gestational age 32 HP:0001518
33 ketoacidosis 32 HP:0001993
34 episodic vomiting 32 HP:0002572
35 increased urinary glycerol 32 HP:0040301

UMLS symptoms related to Glycerol Kinase Deficiency:


seizures

GenomeRNAi Phenotypes related to Glycerol Kinase Deficiency according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Reduced mammosphere formation GR00396-S 8.92 CNR2 GK2 NR0B1 SREBF2

Drugs & Therapeutics for Glycerol Kinase Deficiency

Search Clinical Trials , NIH Clinical Center for Glycerol Kinase Deficiency

Genetic Tests for Glycerol Kinase Deficiency

Genetic tests related to Glycerol Kinase Deficiency:

# Genetic test Affiliating Genes
1 Deficiency of Glycerol Kinase 29 GK

Anatomical Context for Glycerol Kinase Deficiency

MalaCards organs/tissues related to Glycerol Kinase Deficiency:

41
Eye, Liver, Skeletal Muscle

Publications for Glycerol Kinase Deficiency

Articles related to Glycerol Kinase Deficiency:

(show top 50) (show all 62)
# Title Authors Year
1
Cholestasis and Hepatic Iron Deposition in an Infant With Complex Glycerol Kinase Deficiency. ( 28759390 )
2017
2
Complex glycerol kinase deficiency and adrenocortical insufficiency in the neonate. ( 27087023 )
2016
3
Pseudohypertriglyceridemia: two cases of probable glycerol kinase deficiency. ( 23009783 )
2012
4
Complex glycerol kinase deficiency - X-linked contiguous gene syndrome involving congenital adrenal hypoplasia, glycerol kinase deficiency, muscular Duchenne dystrophy and intellectual disability (IL1RAPL gene deletion). ( 23739620 )
2012
5
Glycerol hypersensitivity in a Drosophila model for glycerol kinase deficiency is affected by mutations in eye pigmentation genes. ( 22427807 )
2012
6
Glycerol kinase deficiency in adult hypoglycemic acidemia. ( 21542762 )
2011
7
Anesthesia for a child suffering from a deletion in the Xp21 loci resulting in Duchenne disease, glycerol kinase deficiency, and congenital adrenal hypoplasia. ( 21981102 )
2011
8
The diagnostic difficulties of complex glycerol kinase deficiency. ( 20110216 )
2010
9
Transcriptomic and network component analysis of glycerol kinase in skeletal muscle using a mouse model of glycerol kinase deficiency. ( 19121967 )
2009
10
Weighted gene co-expression network analysis identifies biomarkers in glycerol kinase deficient mice. ( 19546021 )
2009
11
Pseudo-hypertriglyceridaemia: a measurement artefact due to glycerol kinase deficiency. ( 19017842 )
2008
12
Acute liver failure in a child with Epstein-Barr virus infection and undiagnosed glycerol kinase deficiency, mimicking hemophagocytic lymphohistiocytosis. ( 18607276 )
2008
13
Two cases of isolated glycerol kinase deficiency with heterogeneous neurological symptoms. ( 17489818 )
2007
14
[Complex glycerol kinase deficiency in three children]. ( 17937854 )
2007
15
Deletion mapping in Xp21 for patients with complex glycerol kinase deficiency using SNP mapping arrays. ( 17089405 )
2007
16
Glycerol kinase deficiency alters expression of genes involved in lipid metabolism, carbohydrate metabolism, and insulin signaling. ( 17406644 )
2007
17
[Contiguous gene deletion syndrome in Xp21: the association between glycerol kinase deficiency, congenital suprarenal hypoplasia and Duchenne's muscular dystrophy]. ( 17523119 )
2007
18
A multiplex assay for the detection and mapping of complex glycerol kinase deficiency. ( 16887896 )
2006
19
Asymptomatic isolated human glycerol kinase deficiency associated with splice-site mutations and nonsense-mediated decay of mutant RNA. ( 16549535 )
2006
20
Complex glycerol kinase deficiency: an X-linked disorder associated with adrenal hypoplasia congenita. ( 15684452 )
2005
21
Gene therapy for murine glycerol kinase deficiency: importance of murine ortholog. ( 16105550 )
2005
22
Glycerol kinase deficiency presenting with hypodipsia, osmotic diuresis and severe hypernatraemia. ( 16435217 )
2005
23
Glycerol kinase deficiency: follow-up during 20 years, genetics, biochemistry and prognosis. ( 15303806 )
2004
24
IL1RAPL1 is associated with mental retardation in patients with complex glycerol kinase deficiency who have deletions extending telomeric of DAX1. ( 15300857 )
2004
25
Complex glycerol kinase deficiency leads to psychomotor and body-growth failure. ( 15009558 )
2004
26
Glycerol kinase deficiency: residual activity explained by reduced transcription and enzyme conformation. ( 15026783 )
2004
27
Clinical heterogeneity and molecular findings in five Polish patients with glycerol kinase deficiency: investigation of two splice site mutations with computerized splice junction analysis and Xp21 gene-specific mRNA analysis. ( 12855219 )
2003
28
Isolated glycerol kinase deficiency and Fanconi anemia. ( 11241478 )
2001
29
[Glycerol kinase deficiency with dystrophinopathy]. ( 11555931 )
2001
30
Hyperketonaemia in glycerol kinase deficiency. ( 11117440 )
2000
31
Duchenne muscular dystrophy and glycerol kinase deficiency: a rare contiguous gene syndrome. ( 19078586 )
2000
32
AluY insertion (IVS4-52ins316alu) in the glycerol kinase gene from an individual with benign glycerol kinase deficiency. ( 10737976 )
2000
33
Five cases of isolated glycerol kinase deficiency, including two families: failure to find genotype:phenotype correlation. ( 10851254 )
2000
34
Cloning and characterization of a putative human glycerol 3-phosphate permease gene (SLC37A1 or G3PP) on 21q22.3: mutation analysis in two candidate phenotypes, DFNB10 and a glycerol kinase deficiency. ( 11112347 )
2000
35
Late-onset atopic dermatitis in complex glycerol kinase deficiency with chromosome Xp21 region deletion: is there a pathogenic relationship? ( 10026415 )
1999
36
Clinical heterogeneity and novel mutations in the glycerol kinase gene in three families with isolated glycerol kinase deficiency. ( 9719371 )
1998
37
X-linked glycerol kinase deficiency in the mouse leads to growth retardation, altered fat metabolism, autonomous glucocorticoid secretion and neonatal death. ( 9302256 )
1997
38
Glycerol kinase deficiency and adrenal hypoplasia congenita. ( 9266403 )
1997
39
[Syndrome of contiguous gene deletions in Xp-21 (deficiency of the glycerol-kinase complex). The association of Duchenne muscular dystrophy, glycerol kinase deficiency and congenital suprarenal hypoplasia]. ( 9575126 )
1997
40
Glycerol kinase deficiency in two brothers with and without clinical manifestations. ( 9007327 )
1996
41
Mutations and phenotype in isolated glycerol kinase deficiency. ( 8651297 )
1996
42
Dysmorphic features in patients with complex glycerol kinase deficiency. ( 7752004 )
1995
43
Rapid molecular cytogenetic analysis of X-chromosomal microdeletions: fluorescence in situ hybridization (FISH) for complex glycerol kinase deficiency. ( 7573140 )
1995
44
Pseudo-pseudohypertriglyceridemia: a case of increased free glycerol without evidence for glycerol kinase deficiency. ( 7720256 )
1995
45
Complex glycerol kinase deficiency: an unusual cause of salt-wasting in males. ( 7750200 )
1995
46
Congenital adrenal hypoplasia, Duchenne muscular dystrophy, and glycerol kinase deficiency: importance of laboratory investigations in delineating a contiguous gene deletion syndrome. ( 7955386 )
1994
47
Isolated glycerol kinase deficiency in a neonate. ( 7512107 )
1994
48
Cloning of the X-linked glycerol kinase deficiency gene and its identification by sequence comparison to the Bacillus subtilis homologue. ( 8499912 )
1993
49
Screening of glycerol kinase deficiency in patients affected by Duchenne and Becker muscular dystrophy. ( 1395032 )
1992
50
A YAC contig in Xp21 containing the adrenal hypoplasia congenita and glycerol kinase deficiency genes. ( 1301166 )
1992

Variations for Glycerol Kinase Deficiency

UniProtKB/Swiss-Prot genetic disease variations for Glycerol Kinase Deficiency:

75
# Symbol AA change Variation ID SNP ID
1 GK p.Asp446Val VAR_001377 rs132630328
2 GK p.Trp509Arg VAR_010138 rs132630330
3 GK p.Asn294Asp VAR_015433 rs132630331

ClinVar genetic disease variations for Glycerol Kinase Deficiency:

6
(show all 14)
# Gene Variation Type Significance SNP ID Assembly Location
1 GK NM_001205019.1(GK): c.553-1G> C single nucleotide variant Pathogenic rs587776740 GRCh37 Chromosome X, 30714158: 30714158
2 GK NM_001205019.1(GK): c.553-1G> C single nucleotide variant Pathogenic rs587776740 GRCh38 Chromosome X, 30696041: 30696041
3 GK NG_008178.1: g.(71738_72262)_(72384_72493)del deletion Pathogenic GRCh38 Chromosome X, 30720096: 30720851
4 GK NG_008178.1: g.(71738_72262)_(72384_72493)del deletion Pathogenic GRCh37 Chromosome X, 30738213: 30738968
5 GK NM_001205019.1(GK): c.1337A> T (p.Asp446Val) single nucleotide variant Pathogenic rs132630328 GRCh37 Chromosome X, 30738838: 30738838
6 GK NM_001205019.1(GK): c.1337A> T (p.Asp446Val) single nucleotide variant Pathogenic rs132630328 GRCh38 Chromosome X, 30720721: 30720721
7 GK NC_000023.11: g.(30700906_30707555)_(30728743_?)del deletion Pathogenic GRCh38 Chromosome X, 30700906: 30728743
8 GK NM_001205019.1(GK): c.1255C> T (p.Arg419Ter) single nucleotide variant Pathogenic rs132630329 GRCh37 Chromosome X, 30738756: 30738756
9 GK NM_001205019.1(GK): c.1255C> T (p.Arg419Ter) single nucleotide variant Pathogenic rs132630329 GRCh38 Chromosome X, 30720639: 30720639
10 GK NM_001205019.1(GK): c.1525T> C (p.Trp509Arg) single nucleotide variant Pathogenic rs132630330 GRCh37 Chromosome X, 30742241: 30742241
11 GK NM_001205019.1(GK): c.1525T> C (p.Trp509Arg) single nucleotide variant Pathogenic rs132630330 GRCh38 Chromosome X, 30724124: 30724124
12 GK NM_001128127.2(GK): c.42765-52ins316 insertion Pathogenic
13 GK NM_001205019.1(GK): c.880A> G (p.Asn294Asp) single nucleotide variant Pathogenic rs132630331 GRCh37 Chromosome X, 30725701: 30725701
14 GK NM_001205019.1(GK): c.880A> G (p.Asn294Asp) single nucleotide variant Pathogenic rs132630331 GRCh38 Chromosome X, 30707584: 30707584

Expression for Glycerol Kinase Deficiency

Search GEO for disease gene expression data for Glycerol Kinase Deficiency.

Pathways for Glycerol Kinase Deficiency

Pathways related to Glycerol Kinase Deficiency according to KEGG:

37
# Name Kegg Source Accession
1 Glycerolipid metabolism hsa00561
2 PPAR signaling pathway hsa03320

GO Terms for Glycerol Kinase Deficiency

Cellular components related to Glycerol Kinase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 membrane GO:0016020 9.5 CNR2 DMD GK GK2 IL1RAPL1 NR0B1
2 mitochondrial outer membrane GO:0005741 8.8 DMD GK GK2

Biological processes related to Glycerol Kinase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 triglyceride metabolic process GO:0006641 9.32 GK GK2
2 glycerol metabolic process GO:0006071 9.26 GK GK2
3 glycerol-3-phosphate metabolic process GO:0006072 9.16 GK GK2
4 glycerol catabolic process GO:0019563 8.96 GK GK2
5 glycerol-3-phosphate biosynthetic process GO:0046167 8.62 GK GK2

Molecular functions related to Glycerol Kinase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 phosphotransferase activity, alcohol group as acceptor GO:0016773 8.96 GK GK2
2 glycerol kinase activity GO:0004370 8.62 GK GK2

Sources for Glycerol Kinase Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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