Main clinical features of the biallelic condition (POLD3 deficiency)
• Immune: Profound T-cell deficiency presenting as SCID (T cell lymphopenia) or Omenn syndrome (erythroderma, eosinophilia, oligoclonal T cells) with recurrent/severe infections early in life.
• Neurodevelopmental: Developmental delay and progressive neurological features reported.
• Hearing: Congenital sensorineural hearing impairment has been documented.
• Other: Growth and other organ involvement may occur but are not yet well defined due to small case numbers.
• Onset: Early infancy in the reported cases.
• Laboratory/imaging:
On immunophenotyping: low absolute lymphocyte numbers with severe depletion of CD3+ T cells (in a case), reduced levels of naïve T cells and a restricted TCR Vβ repertoire (in Omenn presentation),; low memory B cells have been reported in a case. There is inconsistency in data related to NK cell numbers.
Imaging and histology depend on complications (e.g., infections, transplant sequelae).
Main clinical features of the dominant form (monoallelic POLD3 variant):
• Adult‐onset (typically age ~40–50 yrs) bilateral progressive sensorineural hearing impairment.
• Vestibular dysfunction (balance/vestibular weakness) in some carriers.
• Onset and progression: The dominant form is progressive, post‐lingual, adult‐onset; (in contrast to the recessive form that is early onset).
Other clinical issues: Given the DNA replication/repair role of POLD3, there may be cancer predisposition in carriers (However, this is not yet fully characterized).
POLD3