carnitine palmitoyl transferase II deficiency, severe infantile form

Summary

carnitine palmitoyl transferase II deficiency, severe infantile form (MONDO:0010914) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 269
• Phenotypes (HPO): 29

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		30	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

29 HPO clinical features (Orphanet curated; top 29 by frequency):

HPO ID	Term	Frequency
HP:0012380	Reduced carnitine O-palmitoyltransferase activity	Very frequent (80-99%)
HP:0001324	Muscle weakness	Frequent (30-79%)
HP:0002315	Headache	Frequent (30-79%)
HP:0002574	Episodic abdominal pain	Frequent (30-79%)
HP:0002913	Myoglobinuria	Frequent (30-79%)
HP:0003198	Myopathy	Frequent (30-79%)
HP:0003236	Elevated circulating creatine kinase concentration	Frequent (30-79%)
HP:0003326	Myalgia	Frequent (30-79%)
HP:0003449	Cold-induced muscle cramps	Frequent (30-79%)
HP:0003546	Exercise intolerance	Frequent (30-79%)
HP:0003710	Exercise-induced muscle cramps	Frequent (30-79%)
HP:0003738	Exercise-induced myalgia	Frequent (30-79%)
HP:0008315	Decreased plasma free carnitine	Frequent (30-79%)
HP:0011936	Decreased plasma total carnitine	Frequent (30-79%)
HP:0011964	Intermittent painful muscle spasms	Frequent (30-79%)
HP:0040320	Red-brown urine	Frequent (30-79%)
HP:0045045	Elevated plasma acylcarnitine levels	Frequent (30-79%)
HP:0002910	Elevated circulating hepatic transaminase concentration	Occasional (5-29%)
HP:0003201	Rhabdomyolysis	Occasional (5-29%)
HP:0006929	Hypoglycemic encephalopathy	Occasional (5-29%)
HP:0011675	Arrhythmia	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001305	Dandy-Walker malformation	Occasional (5-29%)
HP:0001397	Hepatic steatosis	Occasional (5-29%)
HP:0001399	Hepatic failure	Occasional (5-29%)
HP:0001638	Cardiomyopathy	Occasional (5-29%)
HP:0001714	Ventricular hypertrophy	Occasional (5-29%)
HP:0001985	Hypoketotic hypoglycemia	Occasional (5-29%)
HP:0002240	Hepatomegaly	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	carnitine palmitoyl transferase II deficiency, severe infantile form
Mondo ID	MONDO:0010914
MeSH	C563462
OMIM	600649
Orphanet	228305
UMLS	C1833511
MedGen	322211
GARD	0017150
Is cancer (heuristic)	no

Also known as: Carnitine palmitoyl transferase deficiency type 2, hepatocardiomuscular form · Carnitine palmitoyl transferase deficiency type 2, severe infantile form · Carnitine palmitoyl transferase II deficiency, hepatocardiomuscular form · carnitine palmitoyl transferase II deficiency, severe infantile form · CPT II deficiency, infantile · CPT2, hepatocardiomuscular form · CPT2, severe infantile form · CPTII, hepatocardiomuscular form · CPTII, severe infantile form

Data availability: 269 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn disorder of energy metabolism › disorder of fatty acid and ketone body metabolism › disorder of carnitine cycle and carnitine transport › carnitine palmitoyl transferase deficiency › carnitine palmitoyltransferase II deficiency › carnitine palmitoyl transferase II deficiency, severe infantile form

Related subtypes (2): carnitine palmitoyl transferase II deficiency, myopathic form, carnitine palmitoyl transferase II deficiency, neonatal form

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

269 retrieved; paginated sample, class counts are floors:

105 uncertain significance, 43 pathogenic/likely pathogenic, 40 conflicting classifications of pathogenicity, 34 likely pathogenic, 19 likely benign, 13 pathogenic, 9 benign/likely benign, 5 benign, 1 conflicting classifications of pathogenicity; other

ClinVar	Variant (HGVS)	Gene	Classification	Review
1067729	NM_000098.3(CPT2):c.1436A>G (p.Tyr479Cys)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073763	NM_000098.3(CPT2):c.28_29insAGCAAG (p.Trp10Ter)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076646	NM_000098.3(CPT2):c.1660C>T (p.Arg554Ter)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
130889	NM_000098.3(CPT2):c.452G>A (p.Arg151Gln)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1322159	NM_000098.3(CPT2):c.202C>T (p.Gln68Ter)	CPT2	Pathogenic	criteria provided, multiple submitters, no conflicts
1358726	NM_000098.3(CPT2):c.451C>T (p.Arg151Trp)	CPT2	Pathogenic	criteria provided, multiple submitters, no conflicts
1451403	NM_000098.3(CPT2):c.1339C>T (p.Gln447Ter)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
166953	NM_000098.3(CPT2):c.886C>T (p.Arg296Ter)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1697214	NM_000098.3(CPT2):c.1711C>A (p.Pro571Thr)	CPT2	Pathogenic	criteria provided, multiple submitters, no conflicts
188753	NM_000098.3(CPT2):c.1369A>T (p.Lys457Ter)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
188991	NM_000098.3(CPT2):c.1348A>T (p.Arg450Ter)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
189042	NM_000098.3(CPT2):c.38del (p.Gly13fs)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
203659	NM_000098.3(CPT2):c.370C>T (p.Arg124Ter)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
203663	NM_000098.3(CPT2):c.1511C>T (p.Pro504Leu)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2048995	NM_000098.3(CPT2):c.1806del (p.Phe602fs)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371697	NM_000098.3(CPT2):c.110_111dup (p.Ser38fs)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371705	NM_000098.3(CPT2):c.1774_1775del (p.Leu592fs)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371712	NM_000098.3(CPT2):c.1545_1548del (p.Phe516fs)	CPT2	Pathogenic	criteria provided, multiple submitters, no conflicts
371729	NM_000098.3(CPT2):c.1345C>T (p.Gln449Ter)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371730	NM_000098.3(CPT2):c.75del (p.Ser26fs)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371750	NM_000098.3(CPT2):c.1414C>T (p.Gln472Ter)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371754	NM_000098.3(CPT2):c.1359_1362del (p.Lys453fs)	CPT2	Pathogenic	criteria provided, single submitter
371762	NM_000098.3(CPT2):c.1046dup (p.Asn349fs)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371775	NM_000098.3(CPT2):c.1345delinsTA (p.Gln449Ter)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
372351	NM_000098.3(CPT2):c.852del (p.Glu285fs)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3731553	NM_000098.3(CPT2):c.1437del (p.Gln478_Tyr479insTer)	CPT2	Pathogenic	criteria provided, single submitter
429340	NM_000098.3(CPT2):c.1324dup (p.Thr442fs)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
495549	NM_000098.3(CPT2):c.98del (p.Gln33fs)	CPT2	Pathogenic	criteria provided, multiple submitters, no conflicts
529859	NM_000098.3(CPT2):c.725_726del (p.His242fs)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
550000	NM_000098.3(CPT2):c.1505T>C (p.Ile502Thr)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CPT2	Definitive	Autosomal recessive	carnitine palmitoyltransferase II deficiency	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CPT2	Orphanet:228302	Carnitine palmitoyl transferase II deficiency, myopathic form
CPT2	Orphanet:228305	Carnitine palmitoyl transferase II deficiency, severe infantile form
CPT2	Orphanet:228308	Carnitine palmitoyl transferase II deficiency, neonatal form
CPT2	Orphanet:263524	Acute necrotizing encephalopathy of childhood

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CPT2	HGNC:2330	ENSG00000157184	P23786	Carnitine O-palmitoyltransferase 2, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CPT2	Carnitine O-palmitoyltransferase 2, mitochondrial	Involved in the intramitochondrial synthesis of acylcarnitines from accumulated acyl-CoA metabolites.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CPT2	Enzyme (other)	yes	2.3.1.21	Carn_acyl_trans, CAT-like_dom_sf, Cho/carn_acyl_trans_1_2

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
jejunal mucosa	1
mucosa of transverse colon	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CPT2	254	ubiquitous	marker	mucosa of transverse colon, jejunal mucosa, right lobe of liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CPT2	2,303

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CPT2	P23786	94.52

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Carnitine shuttle	1	761.3×	0.003	CPT2
PPARA activates gene expression	1	94.4×	0.011	CPT2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
carnitine shuttle	1	4213.0×	0.001	CPT2
carnitine metabolic process	1	2407.4×	0.001	CPT2
long-chain fatty acid metabolic process	1	624.1×	0.003	CPT2
fatty acid beta-oxidation	1	374.5×	0.004	CPT2
positive regulation of cold-induced thermogenesis	1	163.6×	0.007	CPT2
in utero embryonic development	1	72.0×	0.014	CPT2

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
CPT2	PERHEXILINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CPT2	2	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PERHEXILINE	4	CPT2
TEGLICAR	2	CPT2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CPT2	12	Binding:12

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CPT2	2.3.1.21	carnitine O-palmitoyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

2 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
PERHEXILINE	4	CPT2
TEGLICAR	2	CPT2

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CPT2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.