Also known as: Encephalopathy, episodic, due to thiamine pyrophosphokinase deficiency
OMIM#614458 https://omim.org/entry/614458
1. The Disease:
Thiamine metabolism dysfunction syndrome-5 (THMD5) is an autosomal recessive metabolic disorder due to an inborn error of thiamine metabolism.
2. The symptoms:
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. Lack of early signs or symptoms does not exclude the diagnosis.
3. Actions to take in case of early diagnosis:
Biochemical correlation is recommended with high lactate in serum and CSF.
Brain MRI can show T2-hyperintense lesions basal ganglia.
THMD5 is a lifelong disease requiring lifetime management and regular follow-up with a Paediatric Neurology Center Management is provided by multidisciplinary team.
Oral thiamine supplementation stabilized and even improved to some extent after therapy. However, the one patient showed no clear improvement after 2 years of treatment with thiamine.
Genetic counselling is highly recommended for family planning and evaluation of at-risk family members such as siblings.
4. For more information:
Biblio : Eckenweiler M, Mayr JA, Grünert S, Abicht A, Korinthenberg R. Thiamine Treatment and Favorable Outcome in an Infant with Biallelic TPK1 Variants. Neuropediatrics. 2021;52(2):123-125. doi:10.1055/s-0040-1715631