Causes of Premature Graying of Hair
Primary Classification
Premature graying of hair should be divided into genetic/hereditary causes, nutritional deficiencies, autoimmune conditions, and rare syndromic associations. 1, 2, 3
I. Genetic and Hereditary Causes
Telomeropathy-Related Graying
- Pathogenic variants in telomere genes (TERT, TERC, PARN, RTEL1) cause premature graying through abnormal telomere shortening that directly affects hair pigmentation. 2
- These patients may develop pulmonary fibrosis, liver dysfunction, bone marrow abnormalities, and myelodysplastic syndromes alongside the graying. 2
- Refer patients with premature graying plus pulmonary symptoms or cytopenias for genetic evaluation of telomere-related disorders. 2
Familial/Idiopathic Genetic Graying
- Family history is commonly present, indicating major genetic susceptibility even without identified pathogenic variants. 4, 3
- Graying before age 20 in Caucasians, age 25 in Asians, or age 30 in Africans defines premature graying. 5, 3
II. Nutritional Deficiencies
Micronutrient Deficits
- Vitamin D deficiency (<20 ng/mL) shows strong association with hair loss and may contribute to premature graying. 1
- Zinc deficiency impairs hair follicle function, with lower serum zinc levels in affected patients. 1
- Folate deficiency may contribute to hair graying and should be assessed. 1
- Iron deficiency has been documented as a reversible cause of premature graying in case reports. 6
Testing Approach
- Check serum ferritin, vitamin D (target >20 ng/mL), zinc, and folate levels in patients presenting with premature graying. 1, 2
- Supplement identified deficiencies according to standard replacement protocols. 2
III. Autoimmune and Inflammatory Conditions
Autoimmune Associations
- Alopecia areata, an autoimmune T-lymphocyte-mediated condition, associates with premature graying and other autoimmune diseases including thyroid disease, lupus, and vitiligo. 1
- Approximately 20% of alopecia areata patients have family history of autoimmune conditions. 1
Thyroid Dysfunction
- Check TSH levels to rule out thyroid disease, which can cause both hair loss and premature graying. 1
- If TSH is elevated with low free T4, test thyroid peroxidase (TPO) antibodies. 1
IV. Oxidative Stress and Environmental Factors
Extrinsic Factors
- Air pollution, ultraviolet radiation, and smoking generate reactive oxygen species (ROS) that damage melanocytes. 5
- These factors work through direct or indirect mechanisms to impair melanogenesis. 5
Mechanism
- Oxidative stress disrupts the melanogenesis pathway, which depends on tyrosinase enzyme activity in melanosomes. 5
V. Rare Syndromic Causes
Genetic Syndromes with Pigmentary Changes
- Chediak-Higashi Syndrome and Griscelli Syndrome type 2 present with premature graying, oculocutaneous albinism, immunodeficiency, and neurological abnormalities. 2
- Noonan syndrome-like with loose anagen hair (NSLAH) features darkly pigmented skin, ectodermal anomalies, and NS features. 7
Premature Aging Syndromes
- Various progeroid syndromes associate with premature graying as part of accelerated aging phenotypes. 3, 8
VI. Systemic Disease Associations
Metabolic and Endocrine
- Screen for polycystic ovary syndrome (PCOS) in women with premature graying plus signs of androgen excess (acne, hirsutism, irregular periods). 1
- Consider testing prolactin if hyperprolactinemia is suspected. 1
- Perform oral glucose tolerance test if diabetes or insulin resistance is suspected. 1
Atopic Conditions
- Atopy has been associated with premature graying, though the mechanism remains unclear. 3
Common Pitfalls to Avoid
- Do not order excessive laboratory tests when family history and age of onset clearly indicate genetic/familial graying. 1
- Do not miss telomeropathy in patients with premature graying plus respiratory symptoms, cytopenias, or liver dysfunction—these require genetic referral. 2
- Do not overlook nutritional deficiencies as reversible causes—always check vitamin D, zinc, folate, and ferritin. 1, 6
- Do not forget to assess thyroid function, as hypothyroidism is a common treatable cause. 1, 8