HAO1-related glycolate oxidase deficiency is a very rare autosomal recessive inborn error of glyoxylate-precursor metabolism caused by biallelic HAO1 variants. HAO1 encodes hepatic glycolate oxidase, a hydroxyacid oxidase that oxidizes glycolate to glyoxylate. Loss of glycolate oxidase activity causes isolated hyperglycolic aciduria and is generally described as essentially benign; one reported patient had persistent hyperoxaluria of unknown etiology, so hyperoxaluria is modeled as an observed but not yet definitive downstream consequence of HAO1 loss.
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name: HAO1-Related Glycolate Oxidase Deficiency
creation_date: "2026-07-06T06:09:44Z"
description: >-
HAO1-related glycolate oxidase deficiency is a very rare autosomal recessive
inborn error of glyoxylate-precursor metabolism caused by biallelic HAO1
variants. HAO1 encodes hepatic glycolate oxidase, a hydroxyacid oxidase that
oxidizes glycolate to glyoxylate. Loss of glycolate oxidase activity causes
isolated hyperglycolic aciduria and is generally described as essentially
benign; one reported patient had persistent hyperoxaluria of unknown etiology,
so hyperoxaluria is modeled as an observed but not yet definitive downstream
consequence of HAO1 loss.
category: Metabolic Disorder
parents:
- Inborn Error of Metabolism
- Disorder of Glyoxylate and Oxalate Metabolism
synonyms:
- HAO1 deficiency
- Hydroxyacid oxidase 1 deficiency
- Glycolate oxidase deficiency
- Isolated glycolic aciduria
classifications:
icimd_category:
- classification_value: glyoxylate_and_oxalate
notes: >-
ICIMD category 13.1, disorders of glyoxylate and oxalate metabolism.
HAO1/glycolate oxidase acts upstream of glyoxylate and oxalate production.
pathophysiology:
- name: HAO1 Glycolate Oxidase Deficiency
description: >-
Biallelic HAO1 variants impair hepatic glycolate oxidase activity, reducing
oxidation of glycolate to glyoxylate.
role: trigger
genes:
- preferred_term: HAO1
term:
id: hgnc:4809
label: HAO1
molecular_functions:
- preferred_term: glycolate oxidase activity
term:
id: GO:0003973
label: (S)-2-hydroxy-acid oxidase activity
modifier: DECREASED
cellular_components:
- preferred_term: peroxisome
term:
id: GO:0005777
label: peroxisome
biological_processes:
- preferred_term: glyoxylate metabolic process
term:
id: GO:0046487
label: glyoxylate metabolic process
modifier: DECREASED
cell_types:
- preferred_term: hepatocyte
term:
id: CL:0000182
label: hepatocyte
evidence:
- reference: PMID:24996905
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Direct DNA sequencing of glycolate oxidase gene (HAO1) revealed a homozygous c.814-1G>C mutation"
explanation: Supports biallelic HAO1 variation as the genetic lesion in isolated glycolic aciduria.
- reference: PMID:28752386
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Further analysis of the liver biopsy demonstrated absent GO enzyme activity, confirming GO deficiency in this case."
explanation: Directly supports absent glycolate oxidase activity in a human patient.
downstream:
- target: Isolated Hyperglycolic Aciduria
causal_link_type: DIRECT
description: Glycolate oxidase deficiency causes increased urinary glycolate.
evidence:
- reference: PMID:24996905
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "defective splice variant of glycolate oxidase as the cause of isolated asymptomatic glycolic aciduria."
explanation: Directly links defective glycolate oxidase to isolated glycolic aciduria.
- name: Isolated Hyperglycolic Aciduria
description: >-
Glycolate accumulates in urine when HAO1/glycolate oxidase activity is lost.
The initially described affected siblings had markedly elevated glycolic
acid with normal oxalate, citrate, and glycerate, supporting a primarily
biochemical phenotype.
role: central_effector
chemical_entities:
- preferred_term: glycolate
term:
id: CHEBI:29805
label: glycolate
modifier: INCREASED
- preferred_term: glyoxylate
term:
id: CHEBI:36655
label: glyoxylate
modifier: DECREASED
evidence:
- reference: PMID:24996905
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The proband showed markedly increased urinary glycolic acid excretion with normal excretion of oxalate, citrate and glycerate."
explanation: Supports the biochemical phenotype and absence of hyperoxaluria in the index family.
downstream:
- target: Usually Benign Biochemical Disorder
causal_link_type: DIRECT
description: Published human cases describe glycolate oxidase deficiency as essentially benign.
- name: Usually Benign Biochemical Disorder
description: >-
Published cases frame glycolate oxidase deficiency as rare and essentially
benign. Persistent hyperoxaluria has been reported once, but that report
explicitly treated the hyperoxaluria as unexplained rather than a proven
direct consequence of HAO1 loss.
role: consequence
evidence:
- reference: PMID:28752386
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Deficiency of GO is a very rare disorder with only two previously published cases. It is considered to be an essentially benign inborn error of metabolism."
explanation: Supports the benign-biochemical interpretation of HAO1 deficiency.
- reference: PMID:28752386
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: "The present case is unique in that GO deficiency is associated with persistent hyperoxaluria."
explanation: >-
Supports an observed association with persistent hyperoxaluria in one
patient, but the same abstract says the patient also had hyperoxaluria of
unknown etiology, so the causal edge remains cautious.
phenotypes:
- category: Biochemical
name: Hyperglycolic aciduria
description: Markedly increased urinary glycolic acid/glycolate excretion.
evidence:
- reference: PMID:24996905
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The proband showed markedly increased urinary glycolic acid excretion with normal excretion of oxalate, citrate and glycerate."
explanation: Supports hyperglycolic aciduria as the defining biochemical phenotype.
- category: Biochemical
name: Persistent hyperoxaluria in one reported case
description: >-
Persistent hyperoxaluria was reported in one HAO1-deficient patient, but the
etiology was not established and should not be generalized across the
disorder.
phenotype_term:
preferred_term: Hyperoxaluria
term:
id: HP:0003159
label: Hyperoxaluria
evidence:
- reference: PMID:28752386
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: "The present case is unique in that GO deficiency is associated with persistent hyperoxaluria."
explanation: Supports a single-case association, not a definitive or recurrent disease feature.
discussions:
- discussion_id: gap_hao1_hyperoxaluria_causality
prompt: >-
Is persistent hyperoxaluria ever a direct consequence of HAO1/glycolate
oxidase deficiency, or was the reported hyperoxaluria due to another
unresolved cause?
kind: KNOWLEDGE_GAP
status: OPEN
attaches_to:
- pathophysiology#Usually Benign Biochemical Disorder
rationale: >-
The best human source describes glycolate oxidase deficiency as essentially
benign and says the unique patient had hyperoxaluria of unknown etiology.
More cases or functional human data are needed before wiring HAO1 deficiency
into the calcium oxalate nephrolithiasis pathograph.
notes: >-
Package seed 13.1.03.01; OMIM:605023. No exact MONDO disease term was found
in the local MONDO adapter for HAO1-related glycolate oxidase deficiency, so
the entry is named from the gene/enzyme defect and evidence-backed phenotype.