Babies with GA1 are born healthy and may only present with unspecific signs like macrocephaly at birth. Macrocephaly is one of the earliest signs of GA1 so newborns with an enlarged head circumference should be evaluated for GA1. Especially during the age of 3 months until 3 years, most affected babies develop an acute encephalopathic crisis which is triggered by catabolic conditions such as febrile infections, febrile reactions to vaccinations or surgery. These crises result in striatal injury and a complex, mostly dystonic, irreversible and severe movement disorder which is associated with high morbidity and mortality. These babies can experience several symptoms resembling those of cerebral palsy, such as frequently assuming odd positions due to disordered muscle tone (dystonia), involuntary and ceaseless slow, sinuous, writhing (athetotic) or jerky (choreic) movements of the trunk and limbs. Controlling the movement of hands, arms, feet, legs, head, and neck may become very hard and muscle spasms may occur. Repeated stress on the body (such as infection and Fever) can cause symptoms to worsen, but in some children, brain damage will occur without a triggering Fever. Mild to moderate intellectual disabilities may also accompany these symptoms, but some studies have shown that the intellectual ability of a person with GA1, even if untreated, is not or only mildly affected.
In recent years, also other neurologic disease manifestations have been reported such as chronic kidney disease.
For 80-90% of people with GA1, motor symptom development is preventable, but this requires early diagnosis by newborn screening and treatment from birth on. Treatment consists of a low lysine diet and oral carnitine supplementation as well as intermittent emergency treatment during episodes that are likely to induce catabolism. If treatment is delayed or inadequate, motor symptoms begin to manifest acutely or insidiously during infancy or early childhood (before the age of 6) and are often highly variable. A minority of GA1 patients is diagnosed lately in adolescence or even adult age, following the diagnostic work-up of unspecific neurologic symptoms.
If GA1 is not treated, most patients experience an “acute encephalopathic crisis” following preceding trigger symptoms such as:
Possible irreversible neurologic symptoms of an acute encephalopathic crisis are
- Dyskinesia-disorder of involuntary muscle movements
- Dystonia – fixed abnormal postures due to abnormally increased muscle tone
- Orofacial dyskinesia
- Choreoathetosis—irregular migrating contractions, twisting, writhing
- Abnormality of eye movement- nystagmus (involuntary shaking of the eyes)
- Cognitive impairment (highly variable and not seen in many patients)
- Developmental regression
- Opisthotonus- full body spasms
Other possible symptoms noted:
- Intracranial hemorrhage- bleeding in brain
- Neurological speech impairment
- Dilation of the lateral ventricles of brain