CDSP
MCID: CRN239
MIFTS: 62

Carnitine Deficiency, Systemic Primary (CDSP)

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

Aliases & Classifications for Carnitine Deficiency, Systemic Primary

MalaCards integrated aliases for Carnitine Deficiency, Systemic Primary:

Name: Carnitine Deficiency, Systemic Primary 57 13 39
Systemic Primary Carnitine Deficiency 25 20 58 72 36
Renal Carnitine Transport Defect 12 43 29 6 70
Carnitine Uptake Defect 57 12 25 20 43
Carnitine Transporter Deficiency 12 73 20 43
Systemic Carnitine Deficiency 57 73 43 44
Cdsp 57 25 58 72
Primary Carnitine Deficiency 12 20 43
Carnitine Uptake Deficiency 20 43 58
Cud 57 43 58
Carnitine Deficiency, Systemic, Due to Defect in Renal Reabsorption of Carnitine 57 20
Deficiency of Plasma-Membrane Carnitine Transporter 12 58
Systemic Primary Carnitine Deficiency Disease 12 15
Carnitine Deficiency, Primary 57 54
Carnitine Transporter, Plasma-Membrane, Deficiency of 57
Carnitine Plasma-Membrane Transporter Deficiency 20
Systemic Carnitine Deficiency; Scd 57
Carnitine Uptake Defect; Cud 57
Carnitine Transporter Defect 58
Carnitine Transport Defect 25
Spcd 58
Scd 57

Characteristics:

Orphanet epidemiological data:

58
systemic primary carnitine deficiency
Inheritance: Autosomal recessive; Prevalence: 1-9/100000 (Europe),1-9/100000 (United States),1-9/100000 (Japan),1-9/1000000 (Australia),6-9/10000 (Faroe Islands),>1/1000 (Faroe Islands); Age of onset: Infancy,Neonatal; Age of death: normal life expectancy;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
two main presentations
onset in infancy of acute hypoglycemic episodes
onset in childhood (1 to 7 years) of progressive cardiomyopathy and muscle weakness
carnitine supplementation can prevent further episodes and declines in cardiac function


HPO:

31
carnitine deficiency, systemic primary:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Carnitine Deficiency, Systemic Primary

MedlinePlus Genetics : 43 Primary carnitine deficiency is a condition that prevents the body from using certain fats for energy, particularly during periods without food (fasting). Carnitine, a natural substance acquired mostly through the diet, is used by cells to process fats and produce energy.Signs and symptoms of primary carnitine deficiency typically appear during infancy or early childhood and can include severe brain dysfunction (encephalopathy), a weakened and enlarged heart (cardiomyopathy), confusion, vomiting, muscle weakness, and low blood sugar (hypoglycemia). The severity of this condition varies among affected individuals. Some people with primary carnitine deficiency are asymptomatic, which means they do not have any signs or symptoms of the condition. All individuals with this disorder are at risk for heart failure, liver problems, coma, and sudden death.Problems related to primary carnitine deficiency can be triggered by periods of fasting or by illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.

MalaCards based summary : Carnitine Deficiency, Systemic Primary, also known as systemic primary carnitine deficiency, is related to abdominal obesity-metabolic syndrome 1 and reye syndrome, and has symptoms including muscle weakness An important gene associated with Carnitine Deficiency, Systemic Primary is SLC22A5 (Solute Carrier Family 22 Member 5), and among its related pathways/superpathways are Metabolism and Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha). The drugs Quinidine and Dextromethorphan have been mentioned in the context of this disorder. Affiliated tissues include heart, liver and skeletal muscle, and related phenotypes are hepatomegaly and vomiting

Disease Ontology : 12 An amino acid metabolic disorder that involves defective proteins called carnitine transporters, which bring carnitine into cells and prevent its escape from the body preventing the body cannot utilize fats for energy.

GARD : 20 Primary carnitine deficiency is a genetic condition that prevents the body from using certain fats for energy, particularly during periods without food (fasting). The nature and severity of signs and symptoms may vary, but they most often appear during infancy or early childhood and can include severe brain dysfunction ( encephalopathy ), cardiomyopathy, confusion, vomiting, muscle weakness, and hypoglycemia. Some individuals may only have fatigability in adulthood, or no symptoms at all. This condition is caused by mutations in the SLC22A5 gene and is inherited in an autosomal recessive manner. Treatment and prevention of symptoms typically includes oral L-carnitine supplementation.

OMIM® : 57 Primary systemic carnitine deficiency is due to a defect in the high-affinity carnitine transporter expressed in muscle, heart, kidney, lymphoblasts, and fibroblasts. This results in impaired fatty acid oxidation in skeletal and heart muscle. In addition, renal wasting of carnitine results in low serum levels and diminished hepatic uptake of carnitine by passive diffusion, which impairs ketogenesis (Lamhonwah et al., 2002). If diagnosed early, all clinical manifestations of the disorder can be completely reversed by supplementation of carnitine. However, if left untreated, patients will develop lethal heart failure (summary by Shibbani et al., 2014). See also myopathic carnitine deficiency (212160), which is restricted to skeletal muscle. (212140) (Updated 20-May-2021)

KEGG : 36 Systemic primary carnitine deficiency is a rare autosomal recessive disorder characterized by cardiomyopathy, muscle weakness, hypoglycemic hypoketotic coma, and hyperammonemia. Carnitine plays essential roles in the transportation of long-chain fatty acids into the mitochondria for beta-oxidation. This disease is caused by mutations in SLC22A5 that encodes the high-affinity sodium-dependent carnitine transporter, organic cation transporter 2 (OCTN2). The hallmark of systemic primary carnitine deficiency is low concentrations of carnitine in plasma, with accumulation of lipid deposits and renal leakage of carnitine. The clinical symptoms are alleviated dramatically by oral administration of L-carnitine. However, if untreated, patients are precipitated into a crisis with cardiac arrest or Reye-like syndrome that includes acute encephalopathy and fatty degenerative liver failure.

UniProtKB/Swiss-Prot : 72 Systemic primary carnitine deficiency: Autosomal recessive disorder of fatty acid oxidation caused by defective carnitine transport. Present early in life with hypoketotic hypoglycemia and acute metabolic decompensation, or later in life with skeletal myopathy or cardiomyopathy.

Wikipedia : 73 Systemic primary carnitine deficiency (SPCD) is an inborn error of fatty acid transport caused by a... more...

GeneReviews: NBK84551

Related Diseases for Carnitine Deficiency, Systemic Primary

Diseases related to Carnitine Deficiency, Systemic Primary via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 207)
# Related Disease Score Top Affiliating Genes
1 abdominal obesity-metabolic syndrome 1 31.6 HADHA ETFDH ACADM
2 reye syndrome 30.6 SLC22A5 ETFDH CPT2 ACADM
3 muscular lipidosis 30.5 ETFDH ACADS
4 carbonic anhydrase va deficiency, hyperammonemia due to 30.5 SLC25A20 SLC25A13
5 atrial standstill 1 30.4 SLC25A20 SLC22A5 HADHA ACADVL
6 encephalopathy, progressive, early-onset, with episodic rhabdomyolysis 30.1 CPT2 ACADVL
7 multiple carboxylase deficiency 30.0 HADHA HADH ACADM
8 acyl-coa dehydrogenase deficiency 29.9 ETFDH ETFA ACADVL ACADM
9 myopathy 29.8 SLC22A5 HADHA ETFDH ETFB CPT2 ACADVL
10 hypoglycemia 29.7 SLC25A20 SLC22A5 HADHB HADHA HADH CPT2
11 organic acidemia 29.5 GCDH ACADS ACADM
12 sickle cell disease 11.7
13 schnyder corneal dystrophy 11.5
14 ehlers-danlos syndrome, spondylodysplastic type, 3 11.2
15 sickle cell anemia 11.2
16 qt interval, variation in 11.1
17 type 2 diabetes mellitus 11.1
18 cardiac conduction defect 11.1
19 homocystinuria 11.0
20 diabetes mellitus 11.0
21 body mass index quantitative trait locus 11 11.0
22 dysostosis 11.0
23 hemoglobinopathy 11.0
24 subacute cerebellar degeneration 10.9
25 spondylocostal dysostosis 3, autosomal recessive 10.9
26 fetal akinesia deformation sequence 1 10.9
27 fanconi anemia, complementation group d2 10.9
28 fanconi anemia, complementation group a 10.9
29 fetal akinesia deformation sequence 4 10.9
30 non-alcoholic fatty liver disease 10.6
31 visceral steatosis 10.5
32 subjective cognitive decline 10.3
33 autosomal recessive disease 10.3
34 congestive heart failure 10.3
35 cardiac arrhythmia 10.2
36 myoglobinuria, recurrent 10.2 CPT2 ACADVL
37 inflammatory bowel disease 5 10.2 SLC22A5 SLC22A4
38 progressive bulbar palsy 10.2 ETFDH ETFB
39 syncope 10.2
40 cardiac arrest 10.1
41 heart disease 10.1
42 acute chest syndrome 10.1
43 chronic pain 10.1
44 isovaleric acidemia 10.1 HADHA ACADVL ACADS
45 multiple acyl-coa dehydrogenase deficiency, severe neonatal type 10.1 ETFDH ETFB ETFA
46 hemosiderosis 10.1
47 dementia 10.1
48 rare hereditary hemochromatosis 10.1
49 multiple acyl-coa dehydrogenase deficiency, mild type 10.1 ETFDH ETFB ETFA
50 riboflavin deficiency 10.1 ETFDH ETFA ACADS

Graphical network of the top 20 diseases related to Carnitine Deficiency, Systemic Primary:



Diseases related to Carnitine Deficiency, Systemic Primary

Symptoms & Phenotypes for Carnitine Deficiency, Systemic Primary

Human phenotypes related to Carnitine Deficiency, Systemic Primary:

58 31 (show all 30)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hepatomegaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0002240
2 vomiting 58 31 hallmark (90%) Very frequent (99-80%) HP:0002013
3 elevated hepatic transaminase 58 31 hallmark (90%) Very frequent (99-80%) HP:0002910
4 clumsiness 58 31 hallmark (90%) Very frequent (99-80%) HP:0002312
5 confusion 58 31 hallmark (90%) Very frequent (99-80%) HP:0001289
6 neck muscle weakness 58 31 hallmark (90%) Very frequent (99-80%) HP:0000467
7 acute encephalopathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0006846
8 bilateral tonic-clonic seizure with focal onset 31 hallmark (90%) HP:0007334
9 muscle weakness 58 31 Very frequent (99-80%) HP:0001324
10 failure to thrive 31 HP:0001508
11 myopathy 31 HP:0003198
12 cardiomegaly 31 HP:0001640
13 hypoglycemia 31 HP:0001943
14 congestive heart failure 31 HP:0001635
15 hepatic steatosis 31 HP:0001397
16 hypertrophic cardiomyopathy 31 HP:0001639
17 hyperammonemia 31 HP:0001987
18 lethargy 31 HP:0001254
19 encephalopathy 31 HP:0001298
20 coma 31 HP:0001259
21 recurrent hypoglycemia 31 HP:0001988
22 generalized hypotonia 31 HP:0001290
23 endocardial fibroelastosis 31 HP:0001706
24 excessive daytime somnolence 31 HP:0001262
25 decreased plasma carnitine 31 HP:0003234
26 generalized tonic-clonic seizures with focal onset 58 Very frequent (99-80%)
27 hypotonia 31 HP:0001252
28 impaired gluconeogenesis 31 HP:0005959
29 reduced muscle carnitine level 31 HP:0030362
30 decreased carnitine level in liver 31 HP:0045061

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Growth Other:
failure to thrive

Abdomen Liver:
hepatomegaly
steatosis

Laboratory Abnormalities:
hyperammonemia
abnormal liver enzymes
increased urinary carnitine
decreased carnitine in serum, muscle, heart, and liver
impaired carnitine uptake in muscle, heart, kidney, fibroblasts, and lymphocytes
more
Metabolic Features:
hypoketotic hypoglycemic episodes, acute

Muscle Soft Tissue:
muscle weakness
hypotonia
muscle biopsy shows lipid deposition

Cardiovascular Heart:
cardiomegaly
congestive heart failure
hypertrophic cardiomyopathy
fatty infiltration of heart muscle

Neurologic Central Nervous System:
lethargy associated with hypoglycemia
encephalopathy associated with hypoglycemia
coma associated with hypoglycemia
reye syndrome
delay in gross motor development due to weakness

Clinical features from OMIM®:

212140 (Updated 20-May-2021)

UMLS symptoms related to Carnitine Deficiency, Systemic Primary:


muscle weakness

GenomeRNAi Phenotypes related to Carnitine Deficiency, Systemic Primary according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00221-A-2 9.6 CPT2
2 Decreased viability GR00221-A-4 9.6 CPT2
3 Decreased viability GR00249-S 9.6 ACADM ETFA HADH SLC22A5
4 Decreased viability GR00386-A-1 9.6 ACADM ACADS ETFB HADHA HADHB SLC22A2
5 Decreased viability GR00402-S-2 9.6 ACADM ACADS ACADVL CPT2 ETFB SLC22A5
6 Decreased hepcidin::fluc mRNA expression GR00253-A 9.35 ACADS ACADVL ETFDH GCDH SLC25A20

MGI Mouse Phenotypes related to Carnitine Deficiency, Systemic Primary:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 10.13 ABHD5 ACADM ACADS ACADVL CPT2 DECR1
2 liver/biliary system MP:0005370 9.85 ABHD5 ACADM ACADS ACADVL DECR1 HADHA
3 mortality/aging MP:0010768 9.73 ABHD5 ACADM ACADS ACADVL CPT2 ETFDH
4 renal/urinary system MP:0005367 9.23 ACADS GCDH HADH HADHA SLC22A2 SLC22A5

Drugs & Therapeutics for Carnitine Deficiency, Systemic Primary

Drugs for Carnitine Deficiency, Systemic Primary (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 19)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Quinidine Approved, Investigational Phase 2 56-54-2 441074
2
Dextromethorphan Approved Phase 2 125-71-3 5360696 5362449
3
Lithium carbonate Approved Phase 2 554-13-2
4
Simvastatin Approved Phase 2 79902-63-9 54454
5
Valproic acid Approved, Investigational Phase 2 99-66-1 3121
6
Isradipine Approved, Investigational Phase 2 75695-93-1 3784
7 Quinidine gluconate Phase 2
8 Anticholesteremic Agents Phase 2
9 Antimetabolites Phase 2
10 Hydroxymethylglutaryl-CoA Reductase Inhibitors Phase 2
11 Hypolipidemic Agents Phase 2
12 Lipid Regulating Agents Phase 2
13 Vasodilator Agents Phase 2
14 Hormones Phase 2
15 Antihypertensive Agents Phase 2
16 calcium channel blockers Phase 2
17 Calcium, Dietary Phase 2
18
Calcium Nutraceutical Phase 2 7440-70-2 271
19 carnitine

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Sequential Parallel Comparison Design (SPCD) Study to Assess the Efficacy, Safety and Tolerability of AVP-786 (Deuterated [d6]-Dextromethorphan Hydrobromide [d6-DM]/Quinidine Sulfate [Q]) as an Adjunctive Treatment for Patients With Residual Schizophrenia Completed NCT02477670 Phase 2 AVP-786;Placebo
2 Simvastatin Augmentation of Lithium Treatment in Bipolar Depression Terminated NCT01665950 Phase 2 Simvastatin;Placebo
3 Adjunctive Isradipine for the Treatment of Bipolar Depression Terminated NCT01784666 Phase 2 Isradipine;Placebo
4 Fat and Carbohydrate Metabolism During Exercise, With and Without L-carnitine Supplementation in Patients With Carnitine Transporter Deficiency Completed NCT02226419
5 Influence of OCTN2 Variants on Carnitine Status and Plasma Triglycerides Completed NCT00187733

Search NIH Clinical Center for Carnitine Deficiency, Systemic Primary

Cochrane evidence based reviews: systemic carnitine deficiency

Genetic Tests for Carnitine Deficiency, Systemic Primary

Genetic tests related to Carnitine Deficiency, Systemic Primary:

# Genetic test Affiliating Genes
1 Renal Carnitine Transport Defect 29 SLC22A5

Anatomical Context for Carnitine Deficiency, Systemic Primary

MalaCards organs/tissues related to Carnitine Deficiency, Systemic Primary:

40
Heart, Liver, Skeletal Muscle, Bone, Kidney, Small Intestine, Spinal Cord

Publications for Carnitine Deficiency, Systemic Primary

Articles related to Carnitine Deficiency, Systemic Primary:

(show top 50) (show all 137)
# Title Authors PMID Year
1
Maternal systemic primary carnitine deficiency uncovered by newborn screening: clinical, biochemical, and molecular aspects. 25 54 61 6 57
20027113 2010
2
Phenotype and genotype variation in primary carnitine deficiency. 57 54 25 6
11715001 2001
3
Genetic epidemiology of the carnitine transporter OCTN2 gene in a Japanese population and phenotypic characterization in Japanese pedigrees with primary systemic carnitine deficiency. 25 6 57 54
10545605 1999
4
Expanded newborn screening identifies maternal primary carnitine deficiency. 25 57 6
17126586 2007
5
Pharmacological rescue of carnitine transport in primary carnitine deficiency. 57 6 54
16652335 2006
6
Primary carnitine deficiency: novel mutations and insights into the cardiac phenotype. 57 6
23379544 2014
7
Molecular spectrum of SLC22A5 (OCTN2) gene mutations detected in 143 subjects evaluated for systemic carnitine deficiency. 6 25 61
20574985 2010
8
Exclusive cardiac dysfunction in familial primary carnitine deficiency cases: a genotype-phenotype correlation. 57 6
17594400 2007
9
OCTN2 mutation (R254X) found in Saudi Arabian kindred: recurrent mutation or ancient founder mutation? 57 6
15303004 2004
10
Novel OCTN2 mutations: no genotype-phenotype correlations: early carnitine therapy prevents cardiomyopathy. 57 6
12210323 2002
11
Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter. 57 6
9916797 1999
12
Carnitine uptake defect: frameshift mutations in the human plasmalemmal carnitine transporter gene. 57 6
9826541 1998
13
Evidence for linkage of human primary systemic carnitine deficiency with D5S436: a novel gene locus on chromosome 5q. 57 6
9634512 1998
14
Dilated cardiomyopathy caused by plasma membrane carnitine transport defect. 6 57
9700603 1998
15
Impaired skin fibroblast carnitine uptake in primary systemic carnitine deficiency manifested by childhood carnitine-responsive cardiomyopathy. 57 6
2235122 1990
16
Successful carnitine treatment in two siblings having lipid storage myopathy with hypertrophic cardiomyopathy. 6 57
3974805 1985
17
Carnitine levels in 26,462 individuals from the nationwide screening program for primary carnitine deficiency in the Faroe Islands. 25 6
23653224 2014
18
Primary Carnitine Deficiency Presents Atypically with Long QT Syndrome: A Case Report. 25 6
23430858 2012
19
Genotype-phenotype correlation in primary carnitine deficiency. 6 25
21922592 2012
20
Diagnoses of newborns and mothers with carnitine uptake defects through newborn screening. 25 6
20074989 2010
21
Cardiomyopathy and carnitine deficiency. 25 6
18337137 2008
22
Disorders of carnitine transport and the carnitine cycle. 25 6
16602102 2006
23
Silent and symptomatic primary carnitine deficiency within the same family due to identical mutations in the organic cation/carnitine transporter OCTN2. 25 6
14605509 2003
24
Mutations of OCTN2, an organic cation/carnitine transporter, lead to deficient cellular carnitine uptake in primary carnitine deficiency. 6 54 61
10072434 1999
25
Primary carnitine deficiency in a 57-year-old patient with recurrent exertional rhabdomyolysis. 6 61
29895548 2018
26
Biochemical characteristics of newborns with carnitine transporter defect identified by newborn screening in California. 61 6
28711408 2017
27
Primary Carnitine Deficiency - A Rare Treatable Cause of Cardiomyopathy and Massive Hepatomegaly. 6 61
27581592 2017
28
Analysis of genetic mutations in Chinese patients with systemic primary carnitine deficiency. 6 61
25132046 2014
29
SLC22A5 mutations in a patient with systemic primary carnitine deficiency: the first Korean case confirmed by biochemical and molecular investigation. 61 6
23090741 2012
30
Deficiency of the carnitine transporter (OCTN2) with partial N-acetylglutamate synthase (NAGS) deficiency. 54 6
17703373 2007
31
Functional genetic diversity in the high-affinity carnitine transporter OCTN2 (SLC22A5). 6 54
16931768 2006
32
A founder mutation (R254X) of SLC22A5 (OCTN2) in Chinese primary carnitine deficiency patients. 6 54
12204000 2002
33
Identification of two novel mutations in OCTN2 from two Saudi patients with systemic carnitine deficiency. 54 6
12408185 2002
34
Mutations in novel organic cation transporter (OCTN2), an organic cation/carnitine transporter, with differential effects on the organic cation transport function and the carnitine transport function. 6 54
10559218 1999
35
Carnitine transporter OCTN2 mutations in systemic primary carnitine deficiency: a novel Arg169Gln mutation and a recurrent Arg282ter mutation associated with an unconventional splicing abnormality. 61 6
10425211 1999
36
Mutations in the organic cation/carnitine transporter OCTN2 in primary carnitine deficiency. 6 54
10051646 1999
37
Carnitine uptake defect due to a 5'UTR mutation in a pedigree with false positives and false negatives on Newborn screening. 6
31864849 2020
38
A mutation creating an upstream translation initiation codon in SLC22A5 5'UTR is a frequent cause of primary carnitine deficiency. 6
31187905 2019
39
Molecular investigation in Chinese patients with primary carnitine deficiency. 6
31364285 2019
40
Expanded newborn screening for inherited metabolic disorders and genetic characteristics in a southern Chinese population. 6
30904546 2019
41
Application of Next-Generation Sequencing Following Tandem Mass Spectrometry to Expand Newborn Screening for Inborn Errors of Metabolism: A Multicenter Study. 6
30838026 2019
42
Interpretation of Genomic Sequencing Results in Healthy and Ill Newborns: Results from the BabySeq Project. 6
30609409 2019
43
Biochemical, Molecular, and Clinical Characterization of Patients With Primary Carnitine Deficiency via Large-Scale Newborn Screening in Xuzhou Area. 6
30863740 2019
44
Genomic sequencing identifies secondary findings in a cohort of parent study participants. 6
29790872 2018
45
Recessive mutations in NDUFA2 cause mitochondrial leukoencephalopathy. 6
28857146 2018
46
ClinVar: improving access to variant interpretations and supporting evidence. 6
29165669 2018
47
Functional and molecular studies in primary carnitine deficiency. 6
28841266 2017
48
[Genetic diagnosis of 10 neonates with primary carnitine deficiency]. 6
29132460 2017
49
Clinical features and genotyping of patients with primary carnitine deficiency identified by newborn screening. 6
28753539 2017
50
Carnitine transport and fatty acid oxidation. 6
26828774 2016

Variations for Carnitine Deficiency, Systemic Primary

ClinVar genetic disease variations for Carnitine Deficiency, Systemic Primary:

6 (show top 50) (show all 463)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SLC22A5 SLC22A5, 113-BP DEL Deletion Pathogenic 6409 GRCh37:
GRCh38:
2 SLC22A5 SLC22A5, 1-BP INS, 226C Insertion Pathogenic 6410 GRCh37:
GRCh38:
3 SLC22A5 SLC22A5, IVS8AS, G-A, -1 SNV Pathogenic 6412 GRCh37:
GRCh38:
4 SLC22A5 SLC22A5, 1394-BP DEL Deletion Pathogenic 6413 GRCh37:
GRCh38:
5 SLC22A5 NM_003060.3:c.654_825del Deletion Pathogenic 6415 GRCh37:
GRCh38:
6 SLC22A5 NM_003060.4(SLC22A5):c.1051T>C (p.Trp351Arg) SNV Pathogenic 6423 rs68018207 GRCh37: 5:131724712-131724712
GRCh38: 5:132389020-132389020
7 SLC22A5 NM_003060.4(SLC22A5):c.83G>T (p.Ser28Ile) SNV Pathogenic 25354 rs72552724 GRCh37: 5:131705747-131705747
GRCh38: 5:132370055-132370055
8 SLC22A5 NM_003060.4(SLC22A5):c.844del (p.Arg282fs) Deletion Pathogenic 25399 rs386134209 GRCh37: 5:131722731-131722731
GRCh38: 5:132387039-132387039
9 SLC22A5 NM_003060.4(SLC22A5):c.1188T>G (p.Tyr396Ter) SNV Pathogenic 375238 rs1057519051 GRCh37: 5:131726517-131726517
GRCh38: 5:132390825-132390825
10 SLC22A5 NM_003060.4(SLC22A5):c.1172G>A (p.Trp391Ter) SNV Pathogenic 460392 rs1554088165 GRCh37: 5:131726501-131726501
GRCh38: 5:132390809-132390809
11 SLC22A5 NM_003060.4(SLC22A5):c.1462C>T (p.Arg488Cys) SNV Pathogenic 460399 rs377216516 GRCh37: 5:131729379-131729379
GRCh38: 5:132393687-132393687
12 SLC22A5 NM_003060.4(SLC22A5):c.1411C>T (p.Arg471Cys) SNV Pathogenic 460398 rs749282641 GRCh37: 5:131728268-131728268
GRCh38: 5:132392576-132392576
13 SLC22A5 NM_003060.4(SLC22A5):c.818T>C (p.Leu273Pro) SNV Pathogenic 460417 rs760320629 GRCh37: 5:131721185-131721185
GRCh38: 5:132385493-132385493
14 SLC22A5 NM_003060.4(SLC22A5):c.755del (p.Phe252fs) Deletion Pathogenic 460413 rs1554087491 GRCh37: 5:131721121-131721121
GRCh38: 5:132385429-132385429
15 SLC22A5 NM_003060.4(SLC22A5):c.881del (p.Glu294fs) Deletion Pathogenic 460418 rs1554087719 GRCh37: 5:131722773-131722773
GRCh38: 5:132387081-132387081
16 SLC22A5 NM_003060.4(SLC22A5):c.361C>T (p.Gln121Ter) SNV Pathogenic 522874 rs1554086010 GRCh37: 5:131706025-131706025
GRCh38: 5:132370333-132370333
17 SLC22A5 NM_003060.4(SLC22A5):c.797C>T (p.Pro266Leu) SNV Pathogenic 846688 GRCh37: 5:131721164-131721164
GRCh38: 5:132385472-132385472
18 SLC22A5 NC_000005.10:g.(?_132368084)_(132370375_?)del Deletion Pathogenic 833197 GRCh37: 5:131703776-131706067
GRCh38:
19 SLC22A5 NM_003060.4(SLC22A5):c.825-52G>A SNV Pathogenic 842614 GRCh37: 5:131722665-131722665
GRCh38: 5:132386973-132386973
20 SLC22A5 NM_003060.4(SLC22A5):c.1158del (p.Tyr387fs) Deletion Pathogenic 645158 rs1580892402 GRCh37: 5:131726487-131726487
GRCh38: 5:132390795-132390795
21 SLC22A5 NM_003060.4(SLC22A5):c.688T>C (p.Phe230Leu) SNV Pathogenic 460412 rs756650860 GRCh37: 5:131721055-131721055
GRCh38: 5:132385363-132385363
22 SLC22A5 NM_003060.4(SLC22A5):c.1006C>T (p.Arg336Ter) SNV Pathogenic 971074 GRCh37: 5:131724667-131724667
GRCh38: 5:132388975-132388975
23 SLC22A5 NM_003060.4(SLC22A5):c.506G>C (p.Arg169Pro) SNV Pathogenic 945707 GRCh37: 5:131719847-131719847
GRCh38: 5:132384155-132384155
24 SLC22A5 NM_003060.4(SLC22A5):c.825G>A (p.Trp275Ter) SNV Pathogenic 25397 rs386134207 GRCh37: 5:131722717-131722717
GRCh38: 5:132387025-132387025
25 SLC22A5 NM_003060.4(SLC22A5):c.1304del (p.Gly435fs) Deletion Pathogenic 6418 rs386134217 GRCh37: 5:131728159-131728159
GRCh38: 5:132392467-132392467
26 SLC22A5 NM_003060.4(SLC22A5):c.653_654insTATGGCCATCAGGTTGGAG (p.Thr219fs) Insertion Pathogenic 6414 rs1554087461 GRCh37: 5:131721019-131721020
GRCh38: 5:132385327-132385328
27 SLC22A5 NM_003060.4(SLC22A5):c.1365dup (p.Thr456fs) Duplication Pathogenic 236194 rs878853248 GRCh37: 5:131728219-131728220
GRCh38: 5:132392527-132392528
28 SLC22A5 NM_003060.4(SLC22A5):c.845dup (p.Trp283fs) Duplication Pathogenic 659511 rs1580888136 GRCh37: 5:131722736-131722737
GRCh38: 5:132387044-132387045
29 SLC22A5 NM_003060.4(SLC22A5):c.597dup (p.Phe200fs) Duplication Pathogenic 938625 GRCh37: 5:131719937-131719938
GRCh38: 5:132384245-132384246
30 SLC22A5 NM_003060.4(SLC22A5):c.212_222dup (p.Arg75fs) Duplication Pathogenic 949341 GRCh37: 5:131705871-131705872
GRCh38: 5:132370179-132370180
31 SLC22A5 NM_003060.4(SLC22A5):c.1060dup (p.Ile354fs) Duplication Pathogenic 959993 GRCh37: 5:131726388-131726389
GRCh38: 5:132390696-132390697
32 overlap with 12 genes NC_000005.9:g.(?_130497712)_(131729974_?)del Deletion Pathogenic 830550 GRCh37: 5:130497712-131729974
GRCh38:
33 overlap with 4 genes NC_000005.9:g.(?_131436897)_(131729974_?)del Deletion Pathogenic 832924 GRCh37: 5:131436897-131729974
GRCh38:
34 SLC22A5 NC_000005.10:g.(?_132384127)_(132392635_?)del Deletion Pathogenic 649071 GRCh37: 5:131719819-131728327
GRCh38: 5:132384127-132392635
35 SLC22A5 NM_003060.4(SLC22A5):c.137C>T (p.Pro46Leu) SNV Pathogenic 25357 rs377767445 GRCh37: 5:131705801-131705801
GRCh38: 5:132370109-132370109
36 SLC22A5 NM_003060.4(SLC22A5):c.283C>G (p.Leu95Val) SNV Pathogenic 25369 rs386134191 GRCh37: 5:131705947-131705947
GRCh38: 5:132370255-132370255
37 SLC22A5 NM_003060.4(SLC22A5):c.1196G>A (p.Arg399Gln) SNV Pathogenic 6424 rs121908891 GRCh37: 5:131726525-131726525
GRCh38: 5:132390833-132390833
38 SLC22A5 NM_003060.4(SLC22A5):c.652+1G>A SNV Pathogenic 25381 rs386134200 GRCh37: 5:131719994-131719994
GRCh38: 5:132384302-132384302
39 SLC22A5 NM_003060.4(SLC22A5):c.632A>G (p.Tyr211Cys) SNV Pathogenic 6420 rs121908888 GRCh37: 5:131719973-131719973
GRCh38: 5:132384281-132384281
40 SLC22A5 NM_003060.4(SLC22A5):c.1324_1325delinsAT (p.Ala442Ile) Indel Pathogenic 6428 rs267607053 GRCh37: 5:131728181-131728182
GRCh38: 5:132392489-132392490
41 SLC22A5 NM_003060.4(SLC22A5):c.1175_1177TGC[2] (p.Leu394del) Microsatellite Pathogenic 25410 rs386134215 GRCh37: 5:131726502-131726504
GRCh38: 5:132390810-132390812
42 SLC22A5 NM_003060.4(SLC22A5):c.1252C>T (p.Gln418Ter) SNV Pathogenic 373229 rs1057518297 GRCh37: 5:131726581-131726581
GRCh38: 5:132390889-132390889
43 SLC22A5 NM_003060.4(SLC22A5):c.395G>A (p.Trp132Ter) SNV Pathogenic 279949 rs886041277 GRCh37: 5:131714071-131714071
GRCh38: 5:132378379-132378379
44 SLC22A5 NM_003060.4(SLC22A5):c.235del (p.His79fs) Deletion Pathogenic 25359 rs377767447 GRCh37: 5:131705896-131705896
GRCh38: 5:132370204-132370204
45 SLC22A5 NM_003060.4(SLC22A5):c.254_264dup (p.Ile89fs) Duplication Pathogenic 38790 rs377767449 GRCh37: 5:131705914-131705915
GRCh38: 5:132370222-132370223
46 SLC22A5 NM_003060.4(SLC22A5):c.1546_1547dup (p.Leu517fs) Duplication Pathogenic 1032868 GRCh37: 5:131729460-131729461
GRCh38: 5:132393768-132393769
47 SLC22A5 NM_003060.4(SLC22A5):c.844C>T (p.Arg282Ter) SNV Pathogenic 6416 rs121908886 GRCh37: 5:131722736-131722736
GRCh38: 5:132387044-132387044
48 SLC22A5 NM_003060.4(SLC22A5):c.506G>A (p.Arg169Gln) SNV Pathogenic 6421 rs121908889 GRCh37: 5:131719847-131719847
GRCh38: 5:132384155-132384155
49 SLC22A5 NM_003060.4(SLC22A5):c.760C>T (p.Arg254Ter) SNV Pathogenic 6426 rs121908893 GRCh37: 5:131721127-131721127
GRCh38: 5:132385435-132385435
50 SLC22A5 NM_003060.4(SLC22A5):c.51C>G (p.Phe17Leu) SNV Pathogenic 25350 rs11568520 GRCh37: 5:131705715-131705715
GRCh38: 5:132370023-132370023

UniProtKB/Swiss-Prot genetic disease variations for Carnitine Deficiency, Systemic Primary:

72 (show top 50) (show all 73)
# Symbol AA change Variation ID SNP ID
1 SLC22A5 p.Arg169Gln VAR_009252 rs121908889
2 SLC22A5 p.Tyr211Cys VAR_009253 rs121908888
3 SLC22A5 p.Trp283Arg VAR_009254 rs72552729
4 SLC22A5 p.Val446Phe VAR_009255 rs72552733
5 SLC22A5 p.Glu452Lys VAR_009256 rs72552734
6 SLC22A5 p.Pro478Leu VAR_009257 rs72552735
7 SLC22A5 p.Phe17Leu VAR_020347 rs11568520
8 SLC22A5 p.Trp283Cys VAR_022565 rs386134211
9 SLC22A5 p.Ser467Cys VAR_022566 rs60376624
10 SLC22A5 p.Gly15Trp VAR_064110 rs267607052
11 SLC22A5 p.Arg19Pro VAR_064111 rs72552723
12 SLC22A5 p.Asn32Ser VAR_064112 rs72552725
13 SLC22A5 p.Pro46Ser VAR_064113 rs202088921
14 SLC22A5 p.Thr66Pro VAR_064114
15 SLC22A5 p.Arg75Pro VAR_064115 rs757711838
16 SLC22A5 p.Arg83Leu VAR_064116 rs72552726
17 SLC22A5 p.Gly96Ala VAR_064117 rs377767450
18 SLC22A5 p.Asp122Tyr VAR_064118 rs201082652
19 SLC22A5 p.Val123Gly VAR_064119 rs748605096
20 SLC22A5 p.Pro143Leu VAR_064121 rs117858418
21 SLC22A5 p.Arg169Trp VAR_064122 rs121908890
22 SLC22A5 p.Met177Val VAR_064123 rs145068530
23 SLC22A5 p.Leu186Pro VAR_064124 rs386134197
24 SLC22A5 p.Arg227His VAR_064126 rs185551386
25 SLC22A5 p.Phe230Leu VAR_064127 rs756650860
26 SLC22A5 p.Thr232Met VAR_064128 rs114269482
27 SLC22A5 p.Gly234Arg VAR_064129 rs145725852
28 SLC22A5 p.Ala240Thr VAR_064130
29 SLC22A5 p.Gly242Val VAR_064131 rs72552728
30 SLC22A5 p.Arg257Trp VAR_064132 rs386134203
31 SLC22A5 p.Thr264Arg VAR_064133 rs201262157
32 SLC22A5 p.Arg282Gln VAR_064134 rs386134210
33 SLC22A5 p.Ala301Asp VAR_064135 rs72552730
34 SLC22A5 p.Trp351Arg VAR_064137 rs68018207
35 SLC22A5 p.Ser355Leu VAR_064138 rs138563439
36 SLC22A5 p.Tyr358Asn VAR_064139 rs61731073
37 SLC22A5 p.Ser362Leu VAR_064140 rs886042092
38 SLC22A5 p.Pro398Leu VAR_064141 rs144547521
39 SLC22A5 p.Arg399Gln VAR_064142 rs121908891
40 SLC22A5 p.Arg399Trp VAR_064143 rs267607054
41 SLC22A5 p.Thr440Met VAR_064144 rs72552732
42 SLC22A5 p.Ala442Ile VAR_064145 rs267607053
43 SLC22A5 p.Phe443Val VAR_064146
44 SLC22A5 p.Tyr447Cys VAR_064147 rs386134218
45 SLC22A5 p.Pro455Arg VAR_064148 rs140816634
46 SLC22A5 p.Thr468Arg VAR_064149 rs386134221
47 SLC22A5 p.Arg471Cys VAR_064150 rs749282641
48 SLC22A5 p.Arg488Cys VAR_064151 rs377216516
49 SLC22A5 p.Leu507Ser VAR_064152 rs115719854
50 SLC22A5 p.Ser26Asn VAR_066843 rs772578415

Expression for Carnitine Deficiency, Systemic Primary

Search GEO for disease gene expression data for Carnitine Deficiency, Systemic Primary.

Pathways for Carnitine Deficiency, Systemic Primary

Pathways related to Carnitine Deficiency, Systemic Primary according to GeneCards Suite gene sharing:

(show all 17)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.74 SLC25A20 SLC25A13 SLC22A2 HADHB HADHA HADH
2
Show member pathways
12.79 SLC25A20 HADHB HADHA HADH DECR1 CPT2
3
Show member pathways
12.31 HADHB HADHA HADH GCDH CPT2 ACADVL
4 11.95 HADHB HADHA ACADM
5
Show member pathways
11.87 HADHB HADHA HADH ACADS ACADM
6
Show member pathways
11.69 HADHB HADHA HADH
7
Show member pathways
11.65 HADHA HADH GCDH
8 11.45 HADHA HADH GCDH
9
Show member pathways
11.32 HADHB HADHA HADH DECR1 ACADVL ACADS
10 11.28 HADH ACADVL ACADM
11
Show member pathways
11.19 HADHA HADH ACADS
12
Show member pathways
11.05 SLC25A20 HADHB HADHA HADH GCDH DECR1
13 10.97 CPT2 ACADM
14 10.89 HADH DECR1
15
Show member pathways
10.84 HADHB HADHA
16
Show member pathways
10.62 HADHB HADHA HADH ACADM
17 10.54 SLC25A20 CPT2

GO Terms for Carnitine Deficiency, Systemic Primary

Cellular components related to Carnitine Deficiency, Systemic Primary according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial inner membrane GO:0005743 9.76 SLC25A20 SLC25A13 HADHB HADHA ETFDH CPT2
2 mitochondrial membrane GO:0031966 9.62 ETFDH ACADVL ACADM ACAD9
3 mitochondrial matrix GO:0005759 9.61 HADH GCDH ETFDH ETFB ETFA DECR1
4 mitochondrion GO:0005739 9.55 SLC25A20 SLC25A13 SLC22A4 HADHB HADHA HADH
5 mitochondrial nucleoid GO:0042645 9.43 HADHB HADHA ACADVL

Biological processes related to Carnitine Deficiency, Systemic Primary according to GeneCards Suite gene sharing:

(show all 19)
# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 10 HADHA HADH GCDH ETFDH ETFB ETFA
2 lipid metabolic process GO:0006629 9.97 HADHB HADHA HADH DECR1 CPT2 ACADVL
3 fatty acid metabolic process GO:0006631 9.81 HADHB HADHA HADH DECR1 CPT2 ACADVL
4 positive regulation of cold-induced thermogenesis GO:0120162 9.74 HADH DECR1 CPT2
5 electron transport chain GO:0022900 9.73 ETFDH ETFB ETFA
6 respiratory electron transport chain GO:0022904 9.61 ETFDH ETFB ETFA
7 xenobiotic transport GO:0042908 9.58 SLC22A4 SLC22A2
8 amino acid import across plasma membrane GO:0089718 9.58 SLC22A4 SLC22A2
9 carnitine metabolic process GO:0009437 9.58 SLC22A4 CPT2 ACADM
10 carnitine shuttle GO:0006853 9.55 SLC25A20 CPT2
11 organic cation transport GO:0015695 9.54 SLC22A4 SLC22A2
12 carnitine transmembrane transport GO:1902603 9.54 SLC25A20 SLC22A5 SLC22A4
13 cardiolipin acyl-chain remodeling GO:0035965 9.52 HADHB HADHA
14 body fluid secretion GO:0007589 9.51 SLC22A4 SLC22A2
15 fatty acid beta-oxidation using acyl-CoA dehydrogenase GO:0033539 9.5 GCDH ETFDH ETFB ETFA ACADVL ACADS
16 medium-chain fatty acid metabolic process GO:0051791 9.49 ACADM ACAD9
17 carnitine transport GO:0015879 9.48 SLC22A5 SLC22A4
18 quaternary ammonium group transport GO:0015697 9.46 SLC22A5 SLC22A4
19 fatty acid beta-oxidation GO:0006635 9.23 HADHB HADHA HADH DECR1 CPT2 ACADVL

Molecular functions related to Carnitine Deficiency, Systemic Primary according to GeneCards Suite gene sharing:

(show all 16)
# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.85 HADHA HADH GCDH ETFDH ETFA DECR1
2 transmembrane transporter activity GO:0022857 9.83 SLC25A13 SLC22A5 SLC22A4 SLC22A2
3 electron transfer activity GO:0009055 9.72 ETFDH ETFB ETFA
4 oxidoreductase activity, acting on the CH-CH group of donors GO:0016627 9.65 GCDH ACADVL ACADS ACADM ACAD9
5 fatty-acyl-CoA binding GO:0000062 9.62 HADHA GCDH ACADVL ACAD9
6 xenobiotic transmembrane transporter activity GO:0042910 9.56 SLC22A5 SLC22A2
7 enoyl-CoA hydratase activity GO:0004300 9.54 HADHB HADHA
8 3-hydroxyacyl-CoA dehydrogenase activity GO:0003857 9.54 HADHB HADHA HADH
9 acetyl-CoA C-acyltransferase activity GO:0003988 9.51 HADHB HADHA
10 quaternary ammonium group transmembrane transporter activity GO:0015651 9.49 SLC22A5 SLC22A4
11 long-chain-acyl-CoA dehydrogenase activity GO:0004466 9.48 ACADVL ACAD9
12 medium-chain-acyl-CoA dehydrogenase activity GO:0070991 9.46 ACADM ACAD9
13 very-long-chain-acyl-CoA dehydrogenase activity GO:0017099 9.43 ACADVL ACAD9
14 carnitine transmembrane transporter activity GO:0015226 9.4 SLC22A5 SLC22A4
15 acyl-CoA dehydrogenase activity GO:0003995 9.35 GCDH ACADVL ACADS ACADM ACAD9
16 flavin adenine dinucleotide binding GO:0050660 9.17 GCDH ETFDH ETFA ACADVL ACADS ACADM

Sources for Carnitine Deficiency, Systemic Primary

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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