BabyScreen+ newborn screening

Gene: TK2

Green List (high evidence)

three phenotypes with divergent survival:
(1) infantile-onset myopathy (~43%) with severe mitochondrial DNA (mtDNA) depletion, frequent neurological involvement and rapid progression to early mortality (median post-onset survival (POS) 1.00, CI 0.58 to 2.33 years); other organ system involvements have been reported, including an encephalomyopathic presentation with hypotonia, weakness, epilepsy, and microcephaly
(2) childhood-onset myopathy (~40%) with mtDNA depletion, moderate-to-severe progression of generalised weakness and median POS at least 13 years
(3) late-onset myopathy (~17%) with mild limb weakness at onset and slow progression to respiratory insufficiency with median POS of 23 years. Ophthalmoparesis and facial weakness are frequent in adults

Can be treated with deoxycytidine (dC) and deoxythymidine (dT) - should be possible to obtain these for compassionate use (PMID: 31125140)

Created: 23 Dec 2022, 6:02 a.m. | Last Modified: 23 Dec 2022, 6:02 a.m.

Panel Version: 0.1645

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
myopathy; ophthalmoparesis

Publications

• PMID: 29602790
• PMID: 31125140
• PMID: 23385875

I don't know

Strong gene disease association
Progressive weakness
Variable age of onset (infant and childhood onset types both <5 but can also be older onset)
Treatment: In Rx website: deoxycytidine (dC) and deoxythymidine (dT) - single clinical trial? availability in Australia?

Created: 19 Dec 2022, 4 a.m. | Last Modified: 19 Dec 2022, 4 a.m.

Panel Version: 0.1530

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mitochondrial DNA depletion syndrome 2 (myopathic type) MIM#609560

Publications

• PMID: 23230576, PMID: 29602790, PMID: 31125140