A. Etiology

1. Autosomal recessive inheritance
2. Progressive deficiency resulting from inability to absorb sufficient zinc from the diet
3. Long term TPN without zinc supplementation mimics this syndrome

B. Epidemiology

1. Rare condition
2. In breast fed infants presents 2 weeks after weaning
3. In bottle fed infants presents at 4-10 weeks of age

C. Pathogenesis

1. Manifestations reflect zinc's important role in various metabolic pathways
2. Zinc is incorporated into many metalloenzymes
3. Zinc Dependent Pathways: copper, protein, essential fatty acids, and prostaglandins

D. Symptoms

1. Dermatologic
   1. Rash around orifices of the body (oral, anal and perineal areas) and on extremities
   2. Bullous, eczematous, scaly rash with crusting
   3. Reddish discoloration of the hair with diffuse alopecia
2. Gastrointestinal
   1. Chronic diarrhea
   2. Stomatitis and glossitis
3. Ophthalmologic
   1. Photophobia
   2. Conjunctivitis or blepharitis
   3. Corneal dystrophy
4. Development
   1. Mental retardation
   2. Failure to thrive
   3. Short stature
   4. Delayed puberty
5. Immune: impaired lymphocyte function and impaired free radical scavenging

E. Diagnosis

1. Low plasma zinc level
2. Low serum alkaline phosphatase activity
3. Skin biopsy shows parakerotosis and upper epidermal pallor
4. Intestinal mucosal biopsy showing Paneth cell inclusions

F. Treatment

1. Oral zinc replacement (1-2 mg elemental zinc/kg/day)
2. Maximum dose 150 mg per day
3. Super physiologic doses overcome impaired absorption

References

1. Neldner KH and Hambridge KM. 1975. NEJM. 292:897