Menkes Syndrome (Kinky Hair Disease)

Menkes syndrome is a rare X-linked recessive disorder of copper metabolism, characterized by progressive neurodegeneration, connective tissue abnormalities, and distinctive "kinky" hair.

Key Points:

• Incidence: 1 in 100,000 live births
• Primarily affects male infants
• Caused by mutations in ATP7A gene
• Results in copper deficiency
• Usually fatal by age 3 years without treatment

Clinical Manifestations

Early Signs (2-3 months):

• Characteristic pale, sparse, kinky hair (pili torti)
• Feeding difficulties
• Failure to thrive
• Hypotonia
• Temperature instability

Progressive Features:

• Neurological Manifestations:
  • Seizures (often intractable)
  • Developmental regression
  • Hypotonia progressing to spasticity
  • Cerebral and cerebellar degeneration
• Connective Tissue Problems:
  • Skin laxity
  • Joint hypermobility
  • Hernias
  • Arterial tortuosity
• Growth:
  • Poor weight gain
  • Growth retardation
  • Skeletal changes

Diagnostic Approach

Laboratory Studies:

• Serum copper: Markedly decreased
• Serum ceruloplasmin: Very low
• Plasma catecholamine ratios: Elevated
• Genetic testing: ATP7A gene mutations

Imaging Studies:

• MRI findings:
  • Cerebral atrophy
  • White matter abnormalities
  • Tortuous blood vessels
• Radiographs:
  • Osteoporosis
  • Metaphyseal spurs
  • Wormian bones in skull

Other Diagnostic Tests:

• Hair microscopy: Pili torti
• Skin biopsy: Abnormal collagen and elastin
• Placental copper levels (if available)

Treatment and Management

Copper Replacement:

• Copper histidine therapy:
  • Early initiation crucial (before 1 month)
  • Dosing: 250-1000 μg/kg/day subcutaneous
  • Lifelong treatment required

Supportive Care:

• Neurological support:
  • Anticonvulsant medications
  • Physical therapy
  • Occupational therapy
• Nutritional support:
  • Gastrostomy tube if needed
  • Dietary modifications
• Respiratory care:
  • Monitoring for infections
  • Chest physiotherapy

Monitoring:

• Regular copper and ceruloplasmin levels
• Growth parameters
• Developmental assessments
• Neurological examinations

Genetic Aspects

Inheritance Pattern:

• X-linked recessive
• ATP7A gene located on Xq21.1
• Primarily affects males
• Females are carriers

Molecular Genetics:

• Gene function:
  • Codes for copper-transporting ATPase
  • Essential for copper absorption and transport
  • Critical for enzyme function
• Mutations:
  • Over 300 different mutations identified
  • Most lead to complete loss of protein function

Genetic Counseling:

• 25% risk for male offspring of carrier mothers
• Prenatal testing available
• Importance of family screening