Hoyerral Hreidersson syndrome
Question:
11/6/2017
A 6 month-old with normal newborn screen who presented to our hospital at 2 months of age with Pseudomonal otitis media. Birth history significant for IUGR (3lb 12 oz at birth) and FTT, kept in Newborn nursery for 3 weeks due to slow weight gain, discharged at 5 lbs. She had normal skin with no rash at birth but while in nursery developed severe diaper rash, treated with Keflex. Rash rapidly spread to become generalized without improvement on antibiotics. Rash described as erythroderma-like, scaly with plaques.
She was initially breastfed but started on formula at 2 weeks due to poor weight gain. Multiple formula changes due to rash without improvement. Eventually on elemental with no significant improvement. Pediatrician saw in clinic due to worsening rash and labs drawn which significant for eosinophilia (about 5,000). Skin biopsy showed spongiotic dermatitis with eosinophils. W/u for eosinophils negative for parasitic infections, negative for HIV, end organ damage, B12, tryptase. She was found to have undetectable immunoglobulins (interestingly IgG as well). No source of GI or GU loss. Mom’s Igs checked and were normal. She had normal T-cells in number and normal mitogen proliferation. B-cells were very low but detectable. At 6 months, CBC and Immunoglobulins repeated which revealed persistent eosinophilia (7,000-11480) but improvement in IgG (still low at 48), IgM (14) and IgA (Nml to elevated at 114).
No significant family history other than asthma and eczema in multiple members. No recurrent infections. Genetics consulted and requested STAT5b mutation as well as possible SPINK5 (Netherton Syndrome) and DOCK-8 disorders considered. She has not yet received any childhood vaccinations so titers cannot be assessed.
Would you recommend bone marrow biopsy in evaluation of her eosinophilia? Would you consider oral corticosteroids to control her Eosinophilia (though may paradoxically further immune-suppress)? Would you consider IVIG infusion? (Holding as long as she has no further infections as we do not wish to further suppress endogenous production of Ig). Any other work up suggestions and conditions to include in differential?
Answer:
We have asked, Kate Sullivan, MD PhD, one of our PIDD experts for her opinion and here is the response.
"This sounds very much like the severe form of dyskeratosus congenital although there are a few other possibilities.
In DKC, or you will sometimes have this phenotype called Hoyerral Hreidersson syndrome, the NK cells will be low and there will a small cerebellum.
I would put leaky SCID, which you have clearly thought about on the list in spite of the normal T cell numbers. In the Ommens-ish types the T cells can expand look normal.
Both settings are tough."
Here is a link the HH for your review https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526362/pdf/nihms688108.pdf
I hope this has been helpful.
Andrew Murphy, MD FAAAAI