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inborn disorder of pyridoxine metabolism - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

inborn disorder of pyridoxine metabolism

MONDO:0019237

Also known as:inborn error of pyridoxine metabolic processinborn pyridoxine metabolic process disorderrare inborn error of pyridoxine metabolic process

Overview

An inherited metabolic disease that is has its basis in the disruption of pyridoxine metabolic process.

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

No HPO annotations are available for this condition.

GeneReviews

Clinical Guidance

As of 2022, approximately 90 individuals have been identified with pyridox(am)ine 5'-phosphate oxidase (PNPO) deficiency based on the identification of biallelic pathogenic variants in PNPO. The following description of the phenotypic features of PNPO deficiency is based on these reports [, , , , , , , , , , , , , , , , ]. includes a review of all publications up to 2015. also includes a review of all publications up to 2021; some affected individuals included in subsequent follow-up reports may have been counted more than once. Note that the clinical presentations of PNPO deficiency, ALDH7A1 deficiency, and PLPHP deficiency (also referred to as PLPBP or PROSC deficiency) are indistinguishable . The spectrum of the PNPO deficiency phenotype ranges from classic (i.e.

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

Diagnostic Criteria

No consensus clinical diagnostic criteria for pyridox(am)ine 5'-phosphate oxidase (PNPO) deficiency have been published.

Suggestive Findings

PNPO deficiency should be suspected in individuals with the following suggestive clinical phenotypes, positive response to a standardized vitamin B6 trial, supportive laboratory findings, and family history.

Clinical Findings

Classic PNPO deficiency (defined as neonatal onset) in premature infants and neonates

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for inborn disorder of pyridoxine metabolism. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

No clinical practice guidelines for pyridox(am)ine 5'-phosphate oxidase (PNPO) deficiency have been published; however, these are currently being formulated by an international PNPO consortium [Author, personal observation].

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with PNPO deficiency, the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Prognosis

Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.

GeneReviews

Surveillance Guidelines

Table 4. Recommended Surveillance for Individuals with PNPO Deficiency

System/Concern

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

No clinical trials have been registered for inborn disorder of pyridoxine metabolism.

18 publications have been identified in PubMed for inborn disorder of pyridoxine metabolism. Research spans Case Report / Case Series (28%), Basic Science / Preclinical (22%), and Diagnostic / Biomarker (17%).

Research Type	Count	% of Total
Patient case studies	5	28%

Data assembled from 4 of 12 sources · Last updated Sep 19, 2026, 11:57 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

Orphanet

European rare disease database

Orphanet:79192

GARD

Genetic and Rare Diseases Info Center

GARD:18966

Questions for Your Care Team

→Are there specialists or centers of excellence for this condition in my area?
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GeneReviews

Differential Diagnosis

PNPO deficiency must be distinguished from ALDH7A1 deficiency and PLPHP deficiency (also referred to as PLPBP deficiency), as well as other disorders associated with pyridoxine (PN)- and pyridoxal 5'-phosphate (PLP)-responsive seizures . Table 3. Selected Disorders of Interest in the Differential Diagnosis of PNPO Deficiency

Gene	Disorder	Laboratory Features	Response to PN/PLP	Clinical Features
ALDH7A1	Pyridoxine-dependent epilepsy – ALDH7A1 (PDE-ALDH7A1)2	-AASA levels irrespective of treatment w/PN or PLP. May also have levels of pipecolic acid. Low PLP levels in plasma CSF prior to vitamin B6 supplementation.	Szs in affected children respond to supraphysiologic doses of PN (or PLP).	While most newborns have szs soon after birth, some have late onset (i.e., age 2 mos, or as late as adolescence). DD/ID is common, w/more favorable outcome observed in those with late-onset szs.
PLPBP	PLPBP (PLPHP) deficiency2	Secondary biochemical abnormalities suggesting abnormal vitamin B6 metabolism may be present, as may lactic acidosis.	Szs in affected children respond to supraphysiologic doses of PN (or PLP).	Majority have sz onset w/in 1st wk of life; some children present as late as 6 mos.3 Acquired microcephaly, structural brain abnormalities, DD/ID are variable. Pyridoxine (vitamin B6)-responsive seizures4
PGAP3	Hyperphosphatasia w/ID syndrome 42 (OMIM 615716)	serum ALP	Szs may respond to PN.	DD/ID, structural brain anomalies, dysmorphic facies, szs
ALDH4A1	Hyperprolinaemia type II2 (OMIM 239510)	Markedly plasma proline levels as well as P5C in urine	Szs may respond to ASM to PN.	Szs usually manifest beyond neonatal period, may occur w/febrile infections, may respond to common ASM. Persons may have ID or normal intellectual ability.
ALPL	Infantile hypophosphatasia5	Using appropriate pediatric normative reference values, this disorder is suspected w/low serum ALP enzyme activity.	Vitamin B6-responsive seizures may occur.	Clinical signs may be recognized between birth age 6 mos resemble rickets. Prior to availability of enzyme replacement therapy, ~50% succumbed to respiratory failure caused by undermineralization of ribs. Intractable szs may precede biochemical or radiographic manifestations of rickets.
CACNA1A	Developmental epileptic encephalopathy 426 (OMIM 617106)	No assoc biochemical abnormalities	A female w/CACNA1A-related absence epilepsy ataxia responded dramatically to PN.7	—
KCNQ2	KCNQ2-related disorders6	No assoc biochemical abnormalities.	Some w/neonatal epilepsy are vitamin B6 responsive.8	May present w/benign familial neonatal epilepsy or severe neonatal epileptic encephalopathy.

Source: GeneReviews — "PNPO Deficiency"

Kisho

inborn disorder of pyridoxine metabolism

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Evaluations Following Initial Diagnosis

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications

inborn disorder of pyridoxine metabolism

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Evaluations Following Initial Diagnosis

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

Orphanet

GARD

Subtypes

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications