Many factors contribute to this decreased synthesis of IGF-1 including under-nutrition, insufficient blood transfusion with significant periods of anemia, inadequate iron chelation with iron overload in the pituitary gland (GH, LH, FSH, TSH deficiencies), liver (systemic IGF-1 deficiency) and the co-occurrence of other endocrine disorders, such as hypothyroidism and diabetes mellitus. Here, PLOD1 is linked to anemia (phenotype).