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

Rare Disease

inborn disorder of pyrimidine metabolism

MONDO:0019238

Also known as:inborn error of pyrimidine nucleobase metabolic processinborn pyrimidine nucleobase metabolic process disorderpyrimidine metabolic disorder

Overview

ANPM

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

To date, approximately 107 individuals with molecularly confirmed TK2-related mtDNA maintenance defect have been reported [, , , , , , , , , , , ]. The clinical presentation of TK2-related mtDNA maintenance defect is variable; as understanding of the disorder increases, the phenotype continues to broaden. Table 2. Clinical Manifestations of TK2-Related Mitochondrial DNA Maintenance Defect

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

TK2-related mitochondrial DNA (mtDNA) maintenance defect comprises a phenotypic continuum ranging from severe to mild. Three main subtypes of presentation have been described:

Infantile-onset myopathy with neurologic involvement and rapid progression to early death
Juvenile/childhood onset with generalized proximal weakness and survival to adolescence or adulthood
Late-/adult-onset myopathy with facial and limb weakness and mtDNA deletions

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 pyrimidine metabolism. The disease remains an area of unmet medical need.

Gene therapy approaches for inborn disorder of pyrimidine metabolism have been reported in the published literature.

GeneReviews

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs of an individual diagnosed with TK2-related mitochondrial DNA maintenance defect, myopathic form, the following evaluations are recommended, if not completed as part of the diagnostic evaluation. Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with TK2-Related mtDNA Maintenance Defect

Prognosis

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

GeneReviews

Surveillance Guidelines

No disease-specific clinical guidelines are available; treating physicians should consider the evaluations included in . Table 6. Recommended Surveillance for Individuals with TK2-Related mtDNA Maintenance Defect

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 pyrimidine metabolism.

181 publications have been identified in PubMed for inborn disorder of pyrimidine metabolism. Research spans Basic Science / Preclinical (44%), Review / Meta-Analysis (17%), and Clinical Trial Publication (16%).

Research Type	Count	% of Total
Laboratory research	79	44%

Data assembled from 4 of 12 sources · Last updated Sep 20, 2026, 5:38 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

Orphanet

European rare disease database

Orphanet:79193

GARD

Genetic and Rare Diseases Info Center

GARD:18967

Questions for Your Care Team

→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

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Age of Onset	Prevalence	Manifestation	Frequency
Age 2 years(infantile onset)	61/89 (69%)	Hypotonia	55/57 (96%) Elevated serum CK
Cognitive impairment	4/43 (9%) Age 2-18 years(juvenile/childhood onset)	14/89 (16%)	Muscle weakness
Respiratory failure	7/12 (58%) Age 18 years(adult onset)	14/89 (16%)	Dysphagia

System/Concern	Evaluation	Comment
Growth/feeding	Assessment of chewing swallowing ability	Consider referral to OT / feeding therapist /or gastroenterologist.
Ears	Audiology eval	To assess for sensorineural hearing loss
Pulmonary	Pulmonary function eval	Consider referral to pulmonologist.
Neurologic	Neurologic exam	Consider referral to neurologist. EEG
Other	Consultation w/clinical geneticist /or genetic counselor	OT = occupational therapist; PT = physical therapist Treatment of Manifestations Treatment is primarily supportive; management should involve a multidisciplinary team. Table 5.
Treatment of Manifestations in Individuals with TK2-Related mtDNA Maintenance Defect Manifestation/Concern	Treatment	Considerations/Other
Feeding difficulties	Placement of nasogastric or gastrostomy tube	If risk of aspiration is high
Hearing loss	Standard treatment	See Hereditary Hearing Loss and Deafness Overview.
Decreased pulmonary function	Chest physiotherapy1	Consider referral to pulmonologist.
Respiratory failure	Ventilator assistance may be considered.	—
Pulmonary infection	Standard treatment	To prevent deterioration in pulmonary function capacity Muscle weakness/
Restricted mobility	Physical therapy	Consider referral to physical medicine rehabilitation specialist. Wheelchair may be necessary as disease progresses.
Seizures	Standard treatment per neurologist	Education regarding common seizure presentations is appropriate2. 1. Chest physiotherapy may improve pulmonary function and reduce the risk of pulmonary infection.

Kisho

inborn disorder of pyrimidine metabolism

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

Suggestive Findings

Differential Diagnosis

Clinical Trials

Recent Publications

inborn disorder of pyrimidine metabolism

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

Orphanet

GARD

Subtypes

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Suggestive Findings

Differential Diagnosis

Clinical Trials

Recent Publications