[CIS PIDD] [cis-pidd] HLH risk and lysinuric protein intolerance

[CIS-PIDD]

I have been consulted on a 17 y/o M with a new diagnosis of lysinuric
protein intolerance (defect in SLC7A6).  This is a new diagnosis this
hospitalization

He has had failure to thrive his entire life.  He has had issues
with seizures and psychiatric disease.  He has self limited protein and
dairy because of how he felt after.  Due to his nutritional status, a
feeding tube was placed and feeds were started.  1 day later he had altered
mental status and vomiting that improved with holding feedings and worsened
again when restarted.  His serum ammonia was >180 on admission and this
lead to our biochemical geneticist making the diagnosis of LPI.  He also
has a CT scan that is suggestive of pulmonary alveolar proteinosis (bronch
and biopsies pending).

Right now his ferritin is slightly elevated at 1392 and LDH elevated at
311.  Because of the reports of more chronic HLH, further workup is pending

These patients have been described to have a propensity for HLH (in some
reports more of a chronic HLH).  From the literature I cannot elucidate a
clear known mechanism.  But they have trouble with y+L amino acid
transporter that helps mediate arginine efflux in macrophages.  So they
accumulate intracellular arginine (and decreased arginine in the
extracullular micro-environment) that leads to dysregulated NO production.
And this may lead to some of the immune phenotype.

The question from our biochemical geneticist is they want to start a high
citrulline diet.  However there is a theoretical concern (not yet
documented a problem) if you give too much citrulline that you will trap
intracellular arginine in macrophages and potentiate HLH (if the proposed
mechanism there is correct).

Does anyone have further thoughts or experience with this theoretical risk?

-- 

Nicholas Hartog, MD

Allergy and Clinical Immunology

Assistant Professor--Michigan State University College of Human Medicine

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