# Alteração da glicólise

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

## Identificadores

- **ORPHA**: 308459 — https://www.orpha.net/en/disease/detail/308459
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

Doença rara que afeta o metabolismo da glicose, causando atraso de crescimento, ptose, nefropatia e coma hipoglicêmico. Pode apresentar atividade reduzida da 6-fosfofrutoquinase muscular e nível reduzido de peptídeo C.

## Epidemiologia e herança


## Sinais e sintomas (323 fenótipos HPO)

- **Atraso de crescimento** — HPO: HP:0001510
- **Orelhas espessadas** — HPO: HP:0009894
- **Ptose** — HPO: HP:0000508
- **Epicanto** — HPO: HP:0000286
- **Anormalidade regional da pele** — HPO: HP:0011356
- **Nefropatia** — HPO: HP:0000112
- **Nível reduzido de peptídeo C** — HPO: HP:0030795
- **Atividade reduzida da 6-fosfofrutoquinase muscular** — HPO: HP:6000359
- **Artrite** — HPO: HP:0001369
- **Coma hipoglicêmico** — HPO: HP:0001325
- **Cegueira** — HPO: HP:0000618
- **Rigidez muscular induzida por exercício** — HPO: HP:0008967
- **Oligodramnia** — HPO: HP:0001562
- **Hipoplasia renal** — HPO: HP:0000089
- **Hiporreflexia** — HPO: HP:0001265
- **Intolerância ao calor** — HPO: HP:0002046
- **Positividade do anticorpo anti-ácido glutâmico descarboxilase** — HPO: HP:0025329
- **Colelitíase** — HPO: HP:0001081
- **Hipoinsulinemia** — HPO: HP:0040216
- **Crise tônico-clônica bilateral com início focal** — HPO: HP:0007334
- **Apraxia** — HPO: HP:0002186
- **Lesão renal aguda** — HPO: HP:0001919
- **Velocidade de condução nervosa diminuída** — HPO: HP:0000762
- **Positividade de autoanticorpos** — HPO: HP:0030057
- **Glomerulopatia** — HPO: HP:0100820
- **Paralisia diafragmática** — HPO: HP:0006597
- **Prurido** — HPO: HP:0000989
- **Atraso global leve do desenvolvimento** — HPO: HP:0011342
- **Fraqueza muscular progressiva** — HPO: HP:0003323
- **Fraqueza muscular distal do membro inferior** — HPO: HP:0009053
- **Hiperbilirrubinemia** — HPO: HP:0002904
- **Nível de glicosefosfato isomerase diminuído** — HPO: HP:0003568
- **Desconforto respiratório** — HPO: HP:0002098
- **Erupção papular eritematosa generalizada intermitente** — HPO: HP:0007432
- **Amiotrofia do membro inferior** — HPO: HP:0007210
- **Polidipsia** — HPO: HP:0001959
- **Regeneração axonal** — HPO: HP:0003450
- **Anormalidade da mão** — HPO: HP:0001155
- **Desidratação** — HPO: HP:0001944
- **Anormalidade do sistema genital** — HPO: HP:0000078
- _...e mais 283 sintomas. Ver https://raras.org/doenca/alteracao-da-glicolise._

## Genes associados (28)

- **GCK** — Mitogen-activated protein kinase kinase kinase kinase 2 [Disease-causing germline mutation(s) in]
  - Função: Serine/threonine-protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Acts as a MAPK kinase kinase kinase (MAP4K) and is an upstream activator of the stre
- **LDHA** — L-lactate dehydrogenase A chain [Disease-causing germline mutation(s) in]
  - Função: Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+)
- **HNF4A** — Hepatocyte nuclear factor 4-alpha [Disease-causing germline mutation(s) in]
  - Função: Transcriptional regulator which controls the expression of hepatic genes during the transition of endodermal cells to hepatic progenitor cells, facilitating the recruitment of RNA pol II to the promot
- **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
- **HNF1A** — Hepatocyte nuclear factor 1-alpha [Disease-causing germline mutation(s) in]
  - Função: Transcriptional activator that regulates the tissue specific expression of multiple genes, especially in pancreatic islet cells and in liver (By similarity). Binds to the inverted palindrome 5'-GTTAAT
- **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
- **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
- **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
- **LDHB** — L-lactate dehydrogenase B chain [Disease-causing germline mutation(s) in]
  - Função: Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+)
- **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
- **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
- **KCNJ11** — ATP-sensitive inward rectifier potassium channel 11 [Disease-causing germline mutation(s) in]
  - Função: Inward rectifier potassium channel that forms the pore of ATP-sensitive potassium channels (KATP), regulating potassium permeability as a function of cytoplasmic ATP and ADP concentrations in many dif
- **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).
- **PKLR** — Pyruvate kinase PKLR [Disease-causing germline mutation(s) in]
  - Função: Pyruvate kinase that catalyzes the conversion of phosphoenolpyruvate to pyruvate with the synthesis of ATP, and which plays a key role in glycolysis
- **PGAM2** — Phosphoglycerate mutase 2 [Disease-causing germline mutation(s) in]
  - Função: Catalyzes the interconversion of 3- and 2-phosphoglycerate with 2,3-bisphosphoglycerate as the primer of the reaction. Can also catalyze the interconversion of (2R)-2,3-bisphosphoglycerate and (2R)-3-

## Medicamentos em desenvolvimento (1)

- MITAPIVAT — Fase Phase 3 (Pyruvate kinase isozymes R/L activator)
- Fonte: https://platform.opentargets.org/disease/MONDO_0017688

## Ensaios clínicos ativos (5)

- **NCT03641105** [UNKNOWN]: Investigation of the Contents and Prognostic Values of Glucose Metabolism Molecules in Patients With Lung Adenocarcinoma — https://clinicaltrials.gov/study/NCT03641105
- **NCT02856880** [COMPLETED]: A Study to Investigate the Antimicrobial Activity of 2 Test Toothpastes — https://clinicaltrials.gov/study/NCT02856880
- **NCT01935531** [COMPLETED]: Effects of Topical Diclofenac on Tumor Metabolism — https://clinicaltrials.gov/study/NCT01935531
- **NCT01852838** [UNKNOWN]: The Contribution of Induced Glycolysis to the Exhaled Volatile Organic Compounds' (VOCs) Signature in Lung Cancer — https://clinicaltrials.gov/study/NCT01852838
- **NCT01052766** [TERMINATED]: Breathing Synchronized PET/CT Scans for the Detection of Malignant Lung & Liver Lesions and Assessment of Tumor Glycolysis — https://clinicaltrials.gov/study/NCT01052766

## Doenças relacionadas (por similaridade fenotípica)

- [Síndrome MODY](https://raras.org/doenca/sindrome-mody) — ORPHA:552 — 98 sintomas em comum
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- [Neuro-hepatopatia de Navajo](https://raras.org/doenca/neuro-hepatopatia-de-navajo) — ORPHA:255229 — 63 sintomas em comum
- [Diabetes mellitus neonatal permanente isolado](https://raras.org/doenca/diabetes-mellitus-neonatal-permanente-isolado) — ORPHA:99885 — 62 sintomas em comum
- [Deficiência de complexo III isolada](https://raras.org/doenca/deficiencia-de-complexo-iii-isolada) — ORPHA:1460 — 61 sintomas em comum
- [Alteração do metabolismo e excreção de bilirrubina](https://raras.org/doenca/alteracao-do-metabolismo-e-excrecao-de-bilirrubina) — ORPHA:309816 — 58 sintomas em comum
- [Doença túbulo-intersticial renal autossômica dominante HNF1B-relacionada](https://raras.org/doenca/doenca-tubulo-intersticial-renal-autossomica-dominante-hnf1b-relacionada) — ORPHA:93111 — 57 sintomas em comum
- [Anemia sideroblástica](https://raras.org/doenca/anemia-sideroblastica) — ORPHA:1047 — 56 sintomas em comum
- [Doença de Charcot-Marie-Tooth tipo 4](https://raras.org/doenca/doenca-de-charcot-marie-tooth-tipo-4) — ORPHA:64749 — 56 sintomas em comum
- [Anemia sideroblástica genética](https://raras.org/doenca/anemia-sideroblastica-genetica) — ORPHA:98362 — 53 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.

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**Citação sugerida**: Raras.org — Alteração da glicólise. Disponível em: https://raras.org/doenca/alteracao-da-glicolise
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