Background: Canavan disease (CD) is a hereditary neurodegenerative leukodystrophy characterized by the spongiform degeneration of cerebral white matter. It is defined by mutations in the ASPA gene that encodes aspartoacylase (ASPA), the enzyme responsible for hydrolyzing N-acetylaspartic acid (NAA) into acetate and aspartate. Increased NAA and subsequent acetate deficit associated with this condition result in progressive neurological manifestations, including macrocephaly, visuocognitive impairment, and psychomotor retardation. While macrocephaly is a hallmark of the disease, microcephaly is extremely rare in these patients. In this report, we presented a case of CD who was referred to us with global developmental delay and hypotonia, noting that despite the typical macrocephalic phenotype, early head growth may be normal or even reduced in some patients.
Case Report: An 8.5-month-old girl, born to consanguineous parents, was referred to us due to developmental delay. While her birth head circumference was 35 cm (50^th percentile), her circumference at the physical examination was 42 cm (3^rd-5^th percentile), indicating secondary microcephaly. Clinical examination revealed global developmental delay characterized by significant hypotonia and the failure to achieve expected motor and social milestones, including head control, rolling, sitting, and ambulation. Furthermore, the patient exhibited impaired phonation as well as an inability to fixate or follow visual stimuli. Deep tendon reflexes were hyperactive. 
Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) demonstrated diffuse white matter with U-fiber involvements. MRS showed an NAA peak, and notably, high levels of NAA were found in the urine analysis. High-performance liquid chromatography (HPLC) of amino acids yielded normal results. Based on these clinical and neuroimaging findings, a diagnosis was established.
Conclusion: Although CD is rare, microcephaly can be one of the presentations of this disease, in contrast to the diagnostic criteria of the disease that include macrocephaly. A decline in head growth trajectory should raise suspicion for CD even in the absence of macrocephaly.