ZnT2deficient

ZnT2deficient refers to a state in which the zinc transporter ZnT2 (encoded by SLC30A2) has reduced or absent function. ZnT2 is a member of the ZnT family that moves zinc into intracellular secretory compartments, particularly in mammary epithelial cells, where zinc is packaged into milk. In humans, ZnT2 activity in the mammary gland is a key contributor to the zinc content of breast milk and thus to the zinc supply received by exclusively breastfed infants.

Causes of ZnT2 deficiency are mainly genetic. Loss-of-function or deleterious variants in SLC30A2 can impair ZnT2 activity, leading to reduced zinc concentrations in milk. Experimental models have used ZnT2 knockout or knockdown to study the consequences of deficiency. While some cases are familial, the penetrance and clinical presentation can vary, and not all carriers develop overt symptoms.

Clinical implications in infants arise when breastfeeding occurs with low-milk zinc. Infants may present with neonatal zinc deficiency features such as growth faltering, dermatitis, alopecia, diarrhea, and immune dysfunction if zinc intake is not compensated by formula or supplementation. In many cases, zinc supplementation for the infant and/or alternative feeding strategies improve outcomes. In affected mothers, addressing zinc nutrition is important, and dairy or breast milk manipulation may be considered in consultation with clinicians.

Diagnosis involves measuring zinc concentration in breast milk and confirming SLC30A2 variants through genetic testing. Research uses ZnT2-deficient animal models to understand the role of ZnT2 in lactation and systemic zinc homeostasis. See also zinc transporters (SLC30 family) and neonatal zinc deficiency.