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A 6-month-old develops a sharply demarcated, eroded, eczematous rash around the mouth, anus, and on the hands and feet, with sparse hair, in the weeks following weaning from breastmilk. Stools have become loose. Serum zinc is low.
AR; biallelic loss-of-function variants in SLC39A4 encoding the intestinal zinc transporter ZIP4. Loss of ZIP4 → impaired enteric zinc uptake → systemic zinc deficiency.
- Classic triad: acral/periorificial dermatitis, diarrhea, alopecia (the "three Ds")
- Onset is typically masked while breastfeeding (human milk contains a zinc-binding ligand that is absorbed independently of ZIP4) and unmasks around weaning
- Failure to thrive, irritability, recurrent infections, impaired wound healing
- Low serum zinc and low alkaline phosphatase (a zinc-dependent enzyme)
- Low serum zinc and low ALP support the diagnosis; molecular confirmation by SLC39A4 sequencing
- Rule out acquired zinc deficiency (TPN without zinc supplementation, severe malabsorption, restrictive diets)
- Lifelong oral zinc supplementation (typically zinc sulfate or gluconate, ~1-3 mg/kg/day elemental zinc)
- Dramatic clinical response within days; rash and diarrhea resolve, hair regrows
- Periodic monitoring of serum zinc and copper (excess zinc can induce copper deficiency)
- A periorificial/acral rash that started at weaning is the prototypical setup; if zinc therapy reverses the picture in days, the diagnosis is essentially confirmed.
- The "breastmilk masks the disease" pattern is a classic teaching point: formula-fed infants present earlier.
- Acquired zinc deficiency (premature infants on unfortified breast milk, long-term TPN without zinc, anorexia nervosa, gastric bypass) gives an indistinguishable rash. Suspect the inherited form when the picture recurs after stopping supplementation.
"3 Ds of zinc": Dermatitis (acral + periorificial), Diarrhea, Decreased hair (alopecia).
"Weaned and rash-ridden": Symptoms unmask on weaning because breastmilk supplies zinc independently of ZIP4.