What are the causes of premature greying of hair before age 30 in women or 35 in men?

Causes of Premature Grey Hair

Premature grey hair results from a combination of genetic predisposition, telomere-related disorders, oxidative stress, nutritional deficiencies, and autoimmune conditions, with telomeropathies being the most clinically significant cause requiring systematic evaluation.

Genetic and Telomere-Related Causes

Pathogenic variants in telomere maintenance genes represent the most important systemic cause of premature greying, particularly when occurring in the teens or twenties. 1

• Telomere gene mutations (TERT, TERC, RTEL1, PARN, DKC1, NAF1, ZCCHC8, NOP10, TINF2) cause premature greying as part of a broader telomeropathy syndrome 1
• These patients develop greying in their teens or twenties alongside pulmonary fibrosis, bone marrow dysfunction (aplastic anemia, myelodysplastic syndrome, acute myeloid leukemia), liver cirrhosis, and increased cancer risk 1
• When premature greying occurs with family history of pulmonary fibrosis, bone marrow failure, or liver disease, telomere gene testing is indicated 1
• TERT is the most commonly affected gene (10-20% of familial cases), followed by RTEL1, PARN, and TERC (2-5% each) 1

Nutritional Deficiencies

• Vitamin D deficiency shows strong association with hair disorders, with 70% of alopecia patients having levels <20 ng/mL versus 25% of controls 2, 3
• Iron deficiency (ferritin <60 ng/mL) is the most common nutritional deficiency worldwide affecting hair health 2, 4
• Zinc deficiency impairs hair follicle function, with serum zinc levels tending to be lower in patients with hair disorders 2, 3
• Folate deficiency may contribute to premature greying 2

Oxidative Stress and Environmental Factors

• Reactive oxygen species (ROS) generation from smoking, ultraviolet radiation, air pollution, and psychological stress accelerates melanocyte dysfunction 5, 6
• Smoking has been consistently associated with earlier onset of greying 5, 7
• Oxidative stress disrupts melanogenesis by damaging melanocytes and depleting antioxidant defenses in hair follicles 6, 7

Autoimmune and Endocrine Associations

• Approximately 22% of patients with hair disorders have coexisting autoimmune disease and 42% have autoantibodies 3
• Thyroid disease (both hypothyroidism and hyperthyroidism) is associated with premature greying 3, 8
• Vitiligo and alopecia areata frequently coexist with premature greying due to shared autoimmune mechanisms targeting melanocytes 2, 3

Genetic Predisposition (Non-Telomere)

• Familial inheritance accounts for a significant proportion of cases, with genetic variants affecting melanogenesis pathways 9, 5
• Age thresholds defining "premature" vary by ethnicity: before age 20 in Caucasians, 25 in Asians, and 30 in Africans 9, 6

Clinical Evaluation Algorithm

When evaluating premature greying, systematically assess for telomeropathy features first, then nutritional and autoimmune causes:

1. Obtain detailed family history across three generations focusing on pulmonary fibrosis, bone marrow failure, liver cirrhosis, early cancers, and premature greying 1

2. Screen for extrapulmonary telomeropathy manifestations: chronic anemia, macrocytosis, thrombocytopenia, liver dysfunction, and unexplained dyspnea 1

3. Order targeted laboratory testing:

   • TSH and free T4 to exclude thyroid disease 2, 4
   • Serum ferritin (target ≥60 ng/mL for optimal hair health) 2, 4
   • Vitamin D level (deficiency <20 ng/mL) 2, 3
   • Serum zinc and folate 2, 3
   • Complete blood count to screen for bone marrow dysfunction 1

4. Consider telomere length testing and genetic evaluation when greying occurs before age 25 with family history of pulmonary fibrosis, bone marrow failure, or liver disease 1

Common Pitfalls to Avoid

• Failing to recognize telomeropathy: Premature greying in teens/twenties with family history of "idiopathic" pulmonary fibrosis or unexplained cytopenias warrants telomere evaluation 1
• Overlooking nutritional deficiencies as modifiable risk factors, particularly vitamin D and iron 2, 3
• Missing thyroid disease, which commonly causes hair changes including premature greying 2, 4, 8
• Dismissing the psychological impact: premature greying significantly affects self-esteem and quality of life, warranting supportive counseling 9, 7

Treatment Considerations

• No evidence-based treatments effectively reverse established premature greying 6, 7
• Correcting nutritional deficiencies (vitamin D, iron, zinc) may slow progression but will not restore pigment 2, 3
• Hair colorants remain the primary cosmetic solution, though they carry risks of allergic reactions and scalp inflammation 6
• Patients with telomeropathy require multidisciplinary management including pulmonology, hematology, and hepatology referrals 1