BabyScreen+ newborn screening

Gene: TPK1

Green List (high evidence)

Strong gene disease association
Variable age of onset but always under 5years

Thiamine metabolism dysfunction syndrome-5 (THMD5) is an autosomal recessive metabolic disorder due to an inborn error of thiamine metabolism. The phenotype is highly variable, but in general, affected individuals have onset in early childhood of acute encephalopathic episodes associated with increased serum and CSF lactate. These episodes result in progressive neurologic dysfunction manifest as gait disturbances, ataxia, dystonia, and spasticity, which in some cases may result in loss of ability to walk. Cognitive function is usually preserved, although mildly delayed development has been reported. These episodes are usually associated with infection and metabolic decompensation. Some patients may have recovery of some neurologic deficits (Mayr et al., 2011).

Biotin and thiamine therapy - newer evidence (2021) suggests early thiamine therapy may prevent any neurologic deficits.
Sources: Expert list

Created: 16 Mar 2023, 3:54 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Thiamine metabolism dysfunction syndrome 5 (episodic encephalopathy type) MIM#614458

Publications

• PMID: 33086386, 32679198, 22152682, PMID: 33231275