Differential diagnosis

The first step in the differential diagnosis of AGS is to rule out congenital infections belonging to the TORCH spectrum, after which it is necessary to consider other conditions in which basal ganglia calcification is associated with early-onset encephalopathy.
It is worth pointing out that some cases described in the literature as independent clinical entities seem to fit the picture of the early-onset neonatal forms of AGS, for example, many of the cases designated MICS (microcephaly-intracranial calcification syndrome) or “pseudo-TORCH syndrome”, and also the cases referred to as familial systemic lupus erythematosus.
The main forms to be taken into consideration in the differential diagnosis of AGS are Cockayne syndrome, mitochondrial encephalopathies, haemophagocytic lymphohistiocytosis, a particular form of neonatal lupus erythematosus, metabolic encephalopathies with basal ganglia calcification such as parathormone metabolism disorders, biotinidase deficiency, 3-hydroxyisobutyric aciduria, and other unusual syndromes, such as Hoyeraal-Hreidarsson syndrome, cerebroretinal microangiopathy with calcifications and cysts (CRMCC), and band-like calcification with simplified gyration and polymicrogyria (BLC-PMG). Furthermore, in some leukodystrophies (e.g. in Alexander disease, 4H syndrome and the other Pol III-related leukodystrophies, megalencephalic leukoencephalopathy with subcortical cysts, RNAseT2-deficient leukoencephalopathy), the MRI features of impaired frontotemporal white matter and the formation of cysts can initially mimic the abnormalities present in cases of AGS, but ultimately it is the other aspects of the patient's history, the clinical and neuroimaging findings, and the evolution of the case that will indicate the correct diagnosis.