It thus appears reasonable to add sufficient doses of ascorbic acid to the treatment protocol during stresses and other challenges to growth in order to stimulate collagen synthesis and thus prevent lysine breakdown. Tryptophan anabolic pathway enhancement
The conversion of tryptophan to serotonin and other metabolites depends on vitamin B6. If tryptophan catabolism has any impact on brain glutaric acid and other catabolite levels, vitamin B6 levels should be routinely assayed and normalized in the course of the treatment of GA1. Management of intercurrent illnesses
Stress caused by infection, fever or other demands on the body may lead to worsening of the signs and symptoms, with only partial recovery. Prognosis
A 2006 study of 279 patients found that of those with symptoms (185, 66%), 95% had suffered an encephalopathic crises, usually with following brain damage. Of the participants in the study, 49 children died and the median age of death was 6.6 years. A Kaplan–Meier analysis of the data estimated that about 50% of symptomatic people would die by the age of 25. More recent studies provide an updated prognosis whereby individuals affected can, through proper dietary management and carnitine supplementation, manage the disease with a much improved prognosis. Newborn screening has allowed affected patients to avoid crises and live full lives without any injury to the brain. It is essential that patients with the disease be diagnosed at or before birth and that all variables be strictly managed in order to maintain quality of life.
When suspected and in the absence of confirmed diagnosis (through genetic sequencing), it is critical that the individual maintain a diet restrictive of all proteins and that blood sugars be monitored rigorously. The WHO now considers this disease entirely manageable. Epidemiology
GA1 can be described as a metabolic disorder, a neurometabolic disease, a cerebral palsy or a basal ganglia disorder (it may also be misdiagnosed as shaken baby syndrome). Depending on the paradigm adopted, GA1 will mostly be managed with precursor restriction or with neurorehabilitation. So-called "orphan diseases", such as GA1, can be adopted into wider groups of diseases (such as carnitine deficiency diseases, cerebral palsies of diverse origins, basal ganglia disorders, and others); Morton at al. (2003b) emphasize that acute striatal necrosis is a distinctive pathologic feature of at least 20 other disorders of very different etiologies, including, HIV encephalopathy–AIDS dementia complex, pneumococcal meningitis, hypoadrenal crisis, methylmalonic acidemia, propionic acidemia, middle cerebral artery occlusion, hypertensive vasculopathy, acute Mycoplasma pneumoniae infection, 3-nitropropionic acid intoxication, late-onset familial dystonia, cerebrovascular abrupt and severe neonatal asphyxia ("selective neuronal necrosis"). In a cohort of 279 patients who had been reported to have GA1, 185 were symptomatic (two-thirds); being symptomatic was seen as an indication of low treatment efficacy. Screening of those known to be at high risk, neonatal population screening and a diagnosis of macrocephaly are the ways to identify bearers of the GCDH mutation who are not frankly symptomatic.