ORPHA:254875

TK2-related mitochondrial DNA maintenance defect, myopathic form

Synonyms: TK2 deficiency · Thymidine kinase 2 deficiency · TK2d

Type: Disease
Group: Disorder
Inheritance: Autosomal recessive
Age of onset: Infancy, Neonatal
Status: active

A rare mitochondrial DNA depletion syndrome characterized by muscle weakness, and progressive, generalized hypotonia due to depletion of mtDNA in skeletal muscles. Clinical progression ranges from rapid and early fatal course due to respiratory failure, to slowly progressive myopathy over the course of childhood or even early adulthood.

Names in Orphadata languages

12 of 12 languages

Lang	Name	Synonyms
en	TK2-related mitochondrial DNA maintenance defect, myopathic form	TK2 deficiency · Thymidine kinase 2 deficiency · TK2d
fr	Défaut de maintenance de l'ADN mitochondrial associé à TK2, forme myopathique	Déficit en TK2 · TK2d · Déficit en thymidine kinase 2
de	TK2-assoziiertes mitochondriales DNA-Depletionssyndrom, myopathische Form	Thymidinkinase-2-Defizienz · TK2-Mangel
es	Defectos de mantenimiento del ADN mitocondrial asociados al gen TK2, forma miopática	Deficiencia de timidina quinasa 2 · TK2d · Deficiencia de TK2
it	Difetto del mantenimento del DNA mitocondriale correlato a TK2, forma miopatica	Deficit di TK2 · Deficit di timidina chinasi 2 · TK2d
nl	TK2-gerelateerd mitochondriaal DNA-handhavingsdefect, myopathische vorm	TK2d · TK2-deficiëntie · Deficiëntie van thymidinekinase 2
pt	Síndrome de depleção do ADN mitocondrial, forma miopática	Síndrome de depleção do ADNmt, forma miopática
pl	Zespół deplecji mitochondrialnego DNA, postać miopatyczna	Zespół deplecji mtDNA, postać miopatyczna
cs	Syndrom deplece mitochondriální DNA, myopatická forma	Syndrom deplece mtDNA, myopatická forma
uk	Синдром виснаження мітохондріальної ДНК, міопатична форма	Синдром виснаження мтДНК, міопатична форма
zh	肌病型线粒体DNA缺失综合征	线粒体DNA缺失综合征肌病型
tr	Mitokondriyal DNA tükenme sendromu, miyopatik form	mtDNA tükenme sendromu, miyopatik form

Definition in:

Cross-references

qualifier = Orphanet mapping relation

Source	Code	Qualifier	ICD relation	Validation
OMIM	609560	E		validated
ICD-10	G71.3	NTBT	attributed	validated
ICD-11	5C53.20	NTBT	index	validated
MONDO	0012301	E		validated
MeSH	C563698	E		validated
UMLS	C3501891	E		validated

E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.

Classification

Preferential parent (Orphanet linearisation):

ORPHA:68367Rare inborn error of metabolism

Parents in the classifications (4):

ORPHA:79193Disorder of pyrimidine metabolism
rare inborn errors of metabolism; rare genetic diseases
ORPHA:35698Mitochondrial DNA depletion syndrome
rare inborn errors of metabolism; rare genetic diseases
ORPHA:206966Mitochondrial myopathy
rare genetic diseases; rare neurological diseases
ORPHA:68385Neurometabolic disease
rare genetic diseases; rare neurological diseases

Children (3):

Genes

0 direct · 3 via subtypes

Orphanet records no gene directly on this code.

Recorded by Orphanet on subtypes of this disorder:

Gene	Subtype	Association	Status	HGNC	Ensembl	OMIM	Locus	Name	Source of validation
TK2	ORPHA:730740Infantile-onset TK2-related mitochondrial DNA maintenance defect, myopathic form	Disease-causing germline mutation(s) in	Assessed	HGNC:11831	ENSG00000166548	188250	16q21	thymidine kinase 2	23230576[PMID]
TK2	ORPHA:730743Childhood-onset TK2-related mitochondrial DNA maintenance defect, myopathic form	Disease-causing germline mutation(s) in	Assessed	HGNC:11831	ENSG00000166548	188250	16q21	thymidine kinase 2	23230576[PMID]
TK2	ORPHA:730746Late-onset TK2-related mitochondrial DNA maintenance defect, myopathic form	Disease-causing germline mutation(s) in	Assessed	HGNC:11831	ENSG00000166548	188250	16q21	thymidine kinase 2	23230576[PMID]

Prevalence and incidence

2 records

Type	Class	Value	Area	Qualification	Validation	Source
Cases/families		45 cases	Worldwide	Case(s)	Validated	23230576[PMID]
Point prevalence	<1 / 1 000 000	—	Worldwide	Class only	Validated	ORPHANET_23230576[PMID]

Value is Orphadata's ValMoy: the mean estimate per 100 000 for prevalence and incidence, the number of cases or families for case reports.

HPO phenotypes

39 annotations · validated 2024-07-09

HPO	Term (as annotated by Orphanet)	Diagnostic
Obligate (100%)
HP:0003198	Myopathy
Very frequent (99-80%)
HP:0001290	Generalized hypotonia
HP:0002333	Motor deterioration
HP:0001324	Muscle weakness
HP:0002093	Respiratory insufficiency
Frequent (79-30%)
HP:0012432	Chronic fatigue
HP:0002376	Developmental regression
HP:0003698	Difficulty standing
HP:0002460	Distal muscle weakness
HP:0003546	Exercise intolerance
HP:0001531	Failure to thrive in infancy
HP:0008872	Feeding difficulties in infancy
HP:0001288	Gait disturbance
HP:0003324	Generalized muscle weakness
HP:0002197	Generalized-onset seizure
HP:0001265	Hyporeflexia
HP:0001252	Hypotonia
HP:0007105	Infantile encephalopathy
HP:0001270	Motor delay
HP:0009073	Progressive proximal muscle weakness
HP:0006532	Recurrent pneumonia
HP:0002098	Respiratory distress
HP:0002878	Respiratory failure
HP:0002747	Respiratory insufficiency due to muscle weakness
HP:0003202	Skeletal muscle atrophy
Occasional (29-5%)
HP:0001488	Bilateral ptosis
HP:0001283	Bulbar palsy
HP:0100543	Cognitive impairment
HP:0001260	Dysarthria
HP:0002015	Dysphagia
HP:0008610	Infantile sensorineural hearing impairment
HP:0003326	Myalgia
HP:0000597	Ophthalmoparesis
HP:0000590	Progressive external ophthalmoplegia
HP:0008625	Severe sensorineural hearing impairment
HP:0005946	Ventilator dependence with inability to wean
HP:0030319	Weakness of facial musculature
Very rare (<4-1%)
HP:0002650	Scoliosis
HP:0007269	Spinal muscular atrophy

Run the differential on the 5 obligate / very frequent terms

Annotation source: 23230576[PMID]_29735374[PMID]_23932787[PMID]_23968935[PMID]

Sources for this card

Orphanet page: orpha.net/en/disease/detail/254875
This record as JSON: /data/d/254875.json