# Doença do metabolismo do piruvato

> Página oficial: https://raras.org/doenca/doenca-do-metabolismo-do-piruvato
> Fonte: Raras.org — Banco de Dados de Doenças Raras em Português (CC BY-NC-SA 4.0)
> Última atualização: 2026-05-07

## Identificadores

- **ORPHA**: 254746 — https://www.orpha.net/en/disease/detail/254746
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

Uma doença metabólica hereditária que ocorre quando há um problema no processamento do piruvato.

## Epidemiologia e herança


## Sinais e sintomas (484 fenótipos HPO)

- **Defeito do septo ventricular** — HPO: HP:0001629
- **Função ventricular cardíaca anormal** — HPO: HP:0030872
- **Hiperisoleucinemia** — HPO: HP:0010913
- **Concentração diminuída de carnitina circulante** — HPO: HP:0003234
- **Cardiomiopatia** — HPO: HP:0001638
- **Hipercoagulabilidade** — HPO: HP:0100724
- **Aumento da concentração urinária de alfa-cetoglutarato** — HPO: HP:0012402
- **Encefalopatia hepática** — HPO: HP:0002480
- **Anisocitose** — HPO: HP:0011273
- **Dispneia** — HPO: HP:0002094
- **Fissura palpebral ascendente** — HPO: HP:0000582
- **Insuficiência hepática** — HPO: HP:0001399
- **Taquipneia** — HPO: HP:0002789
- **Acuidade visual reduzida** — HPO: HP:0007663
- **Níveis plasmáticos elevados de aminoácidos de cadeia ramificada** — HPO: HP:0008344
- **Saturação elevada da transferrina** — HPO: HP:0012463
- **Anemia hemolítica congênita** — HPO: HP:0004804
- **Aumento do ferro sérico** — HPO: HP:0003452
- **Aumento da concentração circulante de ferritina** — HPO: HP:0003281
- **Face estreita** — HPO: HP:0000275
- **Anormalidade da fisiologia do sistema imunológico** — HPO: HP:0010978
- **Paralisia diafragmática** — HPO: HP:0006597
- **Glomerulopatia** — HPO: HP:0100820
- **Aplasia/Hipoplasia do pâncreas** — HPO: HP:0100800
- **Ducto deferente ausente** — HPO: HP:0012873
- **Cistadenoma papilar do epidídimo** — HPO: HP:0009715
- **Carcinoma de células renais** — HPO: HP:0005584
- **Estenose pilórica** — HPO: HP:0002021
- **Esteatose hepática** — HPO: HP:0001397
- **Artrite** — HPO: HP:0001369
- **Displasia renal multicística** — HPO: HP:0000003
- **Prognatismo mandibular** — HPO: HP:0000303
- **Rim em ferradura** — HPO: HP:0000085
- **Anormalidade da fisiologia do pâncreas endócrino** — HPO: HP:0012093
- **Defeitos osteolíticos da falange média do 4º dedo do pé** — HPO: HP:0100453
- **Paralisia cerebral** — HPO: HP:0100021
- **Lipomas múltiplos** — HPO: HP:0001012
- **Morfologia eritrocitária anormal** — HPO: HP:0001877
- **Dificuldades alimentares na infância** — HPO: HP:0008872
- **Aplasia/Hipoplasia do corpo caloso** — HPO: HP:0007370
- _...e mais 444 sintomas. Ver https://raras.org/doenca/doenca-do-metabolismo-do-piruvato._

## Genes associados (37)

- **PDX1** — Pancreas/duodenum homeobox protein 1 [Disease-causing germline mutation(s) in]
  - Função: Activates insulin, somatostatin, glucokinase, islet amyloid polypeptide and glucose transporter type 2 gene transcription. Particularly involved in glucose-dependent regulation of insulin gene transcr
- **STAT3** — Signal transducer and activator of transcription 3 [Candidate gene tested in]
  - Função: Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:10688651, PubMed:12359225, PubMed:12873986, PubMed:15194
- **LONP1** — Lon protease homolog, mitochondrial [Candidate gene tested in]
  - Função: ATP-dependent serine protease that mediates the selective degradation of misfolded, unassembled or oxidatively damaged polypeptides as well as certain short-lived regulatory proteins in the mitochondr
- **APPL1** — DCC-interacting protein 13-alpha [Candidate gene tested in]
  - Função: Multifunctional adapter protein that binds to various membrane receptors, nuclear factors and signaling proteins to regulate many processes, such as cell proliferation, immune response, endosomal traf
- **NARS2** — Asparaginyl-tRNA synthetase [Candidate gene tested in]
  - Função: Mitochondrial aminoacyl-tRNA synthetase that catalyzes the specific attachment of the asparagine amino acid (aa) to the homologous transfer RNA (tRNA), further participating in protein synthesis (PubM
- **PDP1** — Polyisoprenoid diphosphate/phosphate phosphohydrolase PLPP6 [Disease-causing germline mutation(s) in]
  - Função: Magnesium-independent polyisoprenoid diphosphatase that catalyzes the sequential dephosphorylation of presqualene, farnesyl, geranyl and geranylgeranyl diphosphates (PubMed:16464866, PubMed:19220020,
- **DLAT** — Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial [Disease-causing germline mutation(s) in]
  - Função: The pyruvate dehydrogenase (PDH) complex, catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links cytoplasmic glycolysis and the mitochondrial tricarboxylic acid (TCA)
- **ALDOA** — Fructose-bisphosphate aldolase A [Disease-causing germline mutation(s) in]
  - Função: Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis (PubMed:14766013). In addition, may also
- **ABCC8** — ATP-binding cassette sub-family C member 8 [Disease-causing germline mutation(s) in]
  - Função: Regulator subunit of pancreatic ATP-sensitive potassium channel (KATP), playing a major role in the regulation of insulin release. In pancreatic cells, it forms KATP channels with KCNJ11; KCNJ11 forms
- **HK1** — Hexokinase-1 [Disease-causing germline mutation(s) in]
  - Função: Catalyzes the phosphorylation of various hexoses, such as D-glucose, D-glucosamine, D-fructose, D-mannose and 2-deoxy-D-glucose, to hexose 6-phosphate (D-glucose 6-phosphate, D-glucosamine 6-phosphate
- **GPI** — Glucose-6-phosphate isomerase [Disease-causing germline mutation(s) in]
  - Função: Isomerase that catalyzes the conversion of alpha-D-glucose-6-phosphate to beta-D-fructose-6-phosphate, the second step in glycolysis, and the reverse reaction in gluconeogenesis, within the cytoplasm
- **PFKM** — ATP-dependent 6-phosphofructokinase, muscle type [Disease-causing germline mutation(s) in]
  - Função: Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis
- **PDHB** — Pyruvate dehydrogenase E1 component subunit beta, mitochondrial [Disease-causing germline mutation(s) in]
  - Função: Together with PDHA1 forms the heterotetrameric E1 subunit of the pyruvate dehydrogenase (PDH) complex (PubMed:17474719, PubMed:19081061). The PDH complex catalyzes the overall conversion of pyruvate t
- **PGK1** — Phosphoglycerate kinase 1 [Disease-causing germline mutation(s) in]
  - Função: Catalyzes one of the two ATP producing reactions in the glycolytic pathway via the reversible conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate (PubMed:30323285, PubMed:7391028). Both L- and
- **HNF1B** — Hepatocyte nuclear factor 1-beta [Disease-causing germline mutation(s) in]
  - Função: Transcription factor that binds to the inverted palindrome 5'-GTTAATNATTAAC-3' (PubMed:17924661, PubMed:7900999). Binds to the FPC element in the cAMP regulatory unit of the PLAU gene (By similarity).

## Ensaios clínicos ativos (5)

- **NCT04378075** [TERMINATED]: A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy — https://clinicaltrials.gov/study/NCT04378075
- **NCT01780168** [RECRUITING]: The NIH MINI Study: Metabolism, Infection, and Immunity in Inborn Errors of Metabolism — https://clinicaltrials.gov/study/NCT01780168
- **NCT05175105** [ACTIVE_NOT_RECRUITING]: A Study to Evaluate the Efficacy and Safety of Mitapivat in Pediatric Participants With Pyruvate Kinase Deficiency (PKD) Who Are Not Regularly Transfused, Followed by a 5-Year Extension Period — https://clinicaltrials.gov/study/NCT05175105
- **NCT05144256** [ACTIVE_NOT_RECRUITING]: A Study to Evaluate the Efficacy and Safety of Mitapivat in Pediatric Participants With Pyruvate Kinase Deficiency (PKD) Who Are Regularly Transfused, Followed by a 5-Year Extension Period — https://clinicaltrials.gov/study/NCT05144256
- **NCT07436182** [NOT_YET_RECRUITING]: Mitochondrial Redox Modulation in Newly Diagnosed Type 2 Diabetes: A Randomized Controlled Trial Comparing Imeglimin vs. Metformin Monotherapy — https://clinicaltrials.gov/study/NCT07436182

## Centros de referência no Brasil (21)

- Hospital Universitário Prof. Edgard Santos (HUPES) (Salvador/BA)
- Hospital de Apoio de Brasília (HAB) (Brasília/DF)
- Hospital Estadual Infantil e Maternidade Alzir Bernardino Alves (HIABA) (Vila Velha/ES)
- Hospital das Clínicas da UFG (Goiânia/GO)
- Hospital das Clínicas da UFMG (Belo Horizonte/MG)
- NUPAD / Faculdade de Medicina UFMG (Belo Horizonte/MG)
- Hospital Universitário João de Barros Barreto (Belém/PA)
- Hospital de Clínicas da Universidade Federal de Pernambuco (Recife/PE)
- Instituto de Medicina Integral Prof. Fernando Figueira (IMIP) (Recife/PE)
- Hospital de Clínicas da UFPR (Curitiba/PR)
- Hospital Universitário Pedro Ernesto (HUPE-UERJ) (Rio de Janeiro/RJ)
- Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira (IFF/Fiocruz) (Rio de Janeiro/RJ)
- Hospital Universitário Onofre Lopes (HUOL) (Natal/RN)
- Hospital São Lucas da PUCRS (Porto Alegre/RS)
- Hospital de Clínicas de Porto Alegre (HCPA) (Porto Alegre/RS)
- Hospital Universitário da UFSC (HU-UFSC) (Florianópolis/SC)
- Hospital das Clínicas da FMUSP (São Paulo/SP)
- Hospital de Clínicas da UNICAMP (Campinas/SP)
- Hospital de Clínicas de Ribeirão Preto (HCRP-USP) (Ribeirão Preto/SP)
- Instituto da Criança e do Adolescente (ICr-HCFMUSP) (São Paulo/SP)

## Doenças relacionadas (por similaridade fenotípica)

- [Síndrome MODY](https://raras.org/doenca/sindrome-mody) — ORPHA:552 — 98 sintomas em comum
- [Deficiência de complexo III isolada](https://raras.org/doenca/deficiencia-de-complexo-iii-isolada) — ORPHA:1460 — 91 sintomas em comum
- [Doença do metabolismo de aminoácidos de cadeia ramificada](https://raras.org/doenca/doenca-do-metabolismo-de-aminoacidos-de-cadeia-ramificada) — ORPHA:79197 — 87 sintomas em comum
- [Diabetes mellitus neonatal](https://raras.org/doenca/224) — ORPHA:224 — 84 sintomas em comum
- [Anemia sideroblástica](https://raras.org/doenca/anemia-sideroblastica) — ORPHA:1047 — 79 sintomas em comum
- [Neuro-hepatopatia de Navajo](https://raras.org/doenca/neuro-hepatopatia-de-navajo) — ORPHA:255229 — 78 sintomas em comum
- [Deficiência de piruvato desidrogenase E1-alfa](https://raras.org/doenca/deficiencia-de-piruvato-desidrogenase-e1-alfa) — ORPHA:79243 — 77 sintomas em comum
- [Anemia sideroblástica genética](https://raras.org/doenca/anemia-sideroblastica-genetica) — ORPHA:98362 — 76 sintomas em comum
- [Ataxia espástica](https://raras.org/doenca/ataxia-espastica) — ORPHA:316226 — 76 sintomas em comum
- [Doença do metabolismo da tiamina](https://raras.org/doenca/doenca-do-metabolismo-da-tiamina) — ORPHA:298644 — 75 sintomas em comum

## Importante

O Raras **não diagnostica e não prescreve**. Esta página é educativa e informativa.
Pacientes devem consultar profissionais de saúde qualificados para decisões clínicas.

---

**Citação sugerida**: Raras.org — Doença do metabolismo do piruvato. Disponível em: https://raras.org/doenca/doenca-do-metabolismo-do-piruvato
**Formato HTML**: https://raras.org/doenca/doenca-do-metabolismo-do-piruvato
**Formato RDF/Turtle**: https://raras.org/api/rdf?orpha=254746