FBXL4

Clinical Characteristics

The clinical features of this disease, per organ system, include:

Central Nervous System

  • Encephalopathy
  • Hypotonia
  • Cerebral atrophy
  • Thin corpus callosum
  • Delayed myelination
  • Leukodystrophy
  • White matter abnormalities
  • Brainstem and basal ganglia lesions (some patients)
  • Seizures (some patients)
  • Ataxia (some patients)
  • Dystonia, choreoathetosis (some patients)
  • Swallowing dysfunction
  • Stroke-like episodes

Head and Neck

  • Microcephaly (some patients)
  • Plagiocephaly (some patients)
  • Opthalmological and hearing defects (uncommon), including:
    • Strabismus
    • Cataracts
    • Nystagmus
    • Optic atrophy
    • Reduced vision
    • Sensorineural hearing impairment
  • Dysmorphic facial features (some patients), including:
    • Epicanthus
    • Downslanting palpebral fissures
    • Upslanting palpebral fissures
    • Saddle nose
    • Dolichocephaly
    • Elongated face
    • Everted lower lip
    • Thick eyebrows

Skeletal

  • Scoliosis (some patients)
  • Small feet (some patients)

Cardiovascular (uncommon)

  • Hypertrophic cardio myopathy
  • Arrythmia
  • Pulmonary hypertension
  • Congenital heart disease

Gastrointestinal

  • Gastroesophageal reflux
  • Dysphagia
  • Gastrointestinal dysmotility

Genitourinary

  • Renal tubular acidosis (some patients)
  • Hypospadias

Immune system

  • Recurrent infections (some patients)
  • Neutropenia (some patients)

Other(s)/Abnormal lab findings

  • Increased serum alanine
  • Increased serum ammonia
  • Increased serum lactate
  • Mitochondrial respiratory chain defects (in muscles and fibroblasts)
  • Depletion of mitochondrial DNA
  • Abnormal liver enzymes
  • Lactic Acidosis
  • Global developmental delay
  • Failure to thrive
  • Low birth weight

The onset is usually at birth or early infancy.