Carnitine palmitoyltransferase (CPT) deficiencies

name: Carnitine Palmitoyltransferase Deficiencies
display_name: Carnitine palmitoyltransferase (CPT) deficiencies
creation_date: "2026-08-28T00:00:00Z"
description: >-
  The carnitine palmitoyltransferase deficiencies are the two inherited
  defects of the carnitine shuttle's transferase steps: CPT1A deficiency,
  which blocks formation of long-chain acylcarnitines at the outer
  mitochondrial membrane, and CPT II deficiency, which blocks their
  reconversion to acyl-CoAs at the inner membrane. Both cut off mitochondrial
  long-chain fatty acid beta-oxidation and therefore fail the same
  physiological stress test - fasting, intercurrent illness, or prolonged
  exercise, when tissues must switch to fat as fuel - but they sit on
  opposite sides of the shuttle and leave opposite acylcarnitine signatures.
grouping_basis:
- SHARED_MECHANISM
- SHARED_GENE_FAMILY
grouping_rationale: >-
  Grouped on the shared mechanism (loss of a carnitine palmitoyltransferase
  step of the carnitine shuttle, cutting off long-chain fatty acid
  beta-oxidation) and on the paralogous gene family that names the group.
  The members are deliberately kept as separate Disease entries because the
  two blocks are biochemically and clinically distinct: CPT1A deficiency
  presents as hypoketotic hypoglycemic hepatic encephalopathy of infancy
  with elevated free carnitine and low long-chain acylcarnitines, and has no
  myopathic form; CPT II deficiency accumulates long-chain acylcarnitines
  and spans three forms, including the common adult myopathic form with
  exercise-induced rhabdomyolysis - a presentation CPT1A deficiency does not
  produce. The newborn-screening flags run in opposite directions (high C0
  with low C16/C18 species versus elevated C16/C18:1/C18:2 acylcarnitines), so
  merging the two entries would blur exactly the biochemistry that
  distinguishes them at diagnosis.

  Boundary notes: the neuronal paralog CPT1C is excluded - its variants
  cause a hereditary spastic paraplegia (curated separately as
  CPT1C-Related Hereditary Spastic Paraplegia) with no fatty acid oxidation
  failure phenotype, so gene-family kinship alone does not admit it.
  Carnitine-acylcarnitine translocase (SLC25A20) deficiency shares the
  shuttle and much of the clinical picture but is not a carnitine
  palmitoyltransferase deficiency; it belongs beside this grouping in any
  future carnitine-shuttle or long-chain FAO disorder grouping, not inside
  it.
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0700284
      label: carnitine palmitoyl transferase deficiency
    mapping_predicate: skos:exactMatch
    mapping_source: MONDO
    mapping_justification: >-
      The grouping concept corresponds exactly to the MONDO carnitine
      palmitoyl transferase deficiency class, whose descendants are the two
      members and the clinical forms of CPT II deficiency. CPT1C-related
      disease is not a descendant of this class, matching its exclusion
      here.
membership_criteria:
- description: >-
    Every member is caused by deficiency of a carnitine palmitoyltransferase
    of the mitochondrial carnitine shuttle (CPT1A or CPT2), impairing the
    shuttle and long-chain fatty acid beta-oxidation.
  criteria_semantics: NECESSARY
  logic:
    operator: AND
    operands:
    - operator: OR
      description: A carnitine palmitoyltransferase gene is the causal locus.
      operands:
      - criterion_predicate: HAS_GENE
        description: Deficiency of liver-type CPT1 (CPT1A).
        gene:
          preferred_term: CPT1A
          term:
            id: hgnc:2328
            label: CPT1A
      - criterion_predicate: HAS_GENE
        description: Deficiency of CPT II (CPT2).
        gene:
          preferred_term: CPT2
          term:
            id: hgnc:2330
            label: CPT2
    - criterion_predicate: HAS_BIOLOGICAL_PROCESS
      description: The carnitine shuttle is impaired.
      biological_processes:
      - preferred_term: Carnitine shuttle
        term:
          id: GO:0006853
          label: carnitine shuttle
        modifier: DECREASED
members:
- member: Carnitine Palmitoyltransferase 1A Deficiency
  member_type: DISEASE
  display_name: CPT1A deficiency (outer-membrane block)
  differentiating_mechanisms:
  - description: >-
      The block is at the outer mitochondrial membrane, before acylcarnitine
      formation: long-chain acyl-CoAs cannot be converted to acylcarnitines,
      so free carnitine is high and long-chain acylcarnitine species are low
      - the inverse of the CPT II signature. The phenotype is hepatic
      (fasting-provoked hypoketotic hypoglycemia and hepatic
      encephalopathy), with a distinctive arctic founder allele (P479L);
      there is no
      rhabdomyolysis-dominant adult form.
    gene:
      preferred_term: CPT1A
      term:
        id: hgnc:2328
        label: CPT1A
- member: Carnitine Palmitoyltransferase II Deficiency
  member_type: DISEASE
  display_name: CPT II deficiency (inner-membrane block)
  differentiating_mechanisms:
  - description: >-
      The block is at the inner mitochondrial membrane, after acylcarnitine
      import: long-chain acylcarnitines accumulate (elevated C16, C18:1,
      and C18:2 species, high (C16+C18:1)/C2 ratio) and are themselves
      membrane-toxic. The clinical spectrum spans lethal neonatal and
      severe infantile hepatocardiomuscular forms through the common adult
      myopathic form with exercise-, fasting-, or illness-triggered
      rhabdomyolysis and myoglobinuria - the presentation that most sharply
      separates it from CPT1A deficiency.
    gene:
      preferred_term: CPT2
      term:
        id: hgnc:2330
        label: CPT2
notes: >-
  Created from the stub-queue lump/split review: the seeded stub for
  MONDO:0700284 (carnitine palmitoyl transferase deficiency) resolved as
  entry_type GROUPING because both constituent diseases are already curated
  as separate entries and the label names their union - two paralogous
  transferase deficiencies on opposite sides of one shuttle, with opposite
  acylcarnitine signatures. Both members annotate GO:0006853 (carnitine
  shuttle), so the biological-process leaf is machine-checkable.