Neonatal neuroimaging findings in inborn errors of metabolism

Abstract

Individually, metabolic disorders are rare, but overall they account for a significant number of neonatal disorders affecting the central nervous system. The neonatal clinical manifestations of inborn errors of metabolism (IEMs) are characterized by nonspecific systemic symptoms that may mimic more common acute neonatal disorders like sepsis, severe heart insufficiency, or neonatal hypoxic-ischemic encephalopathy. Certain IEMs presenting in the neonatal period may also be complicated by sepsis and cardiomyopathy. Early diagnosis is mandatory to prevent death and permanent long-term neurological impairments. Although neuroimaging findings are rarely specific, they play a key role in suggesting the correct diagnosis, limiting the differential diagnosis, and may consequently allow early initiation of targeted metabolic and genetic laboratory investigations and treatment. Neuroimaging may be especially helpful to distinguish metabolic disorders from other more common causes of neonatal encephalopathy, as a newborn may present with an IEM prior to the availability of the newborn screening results. It is therefore important that neonatologists, pediatric neurologists, and pediatric neuroradiologists are familiar with the neuroimaging findings of metabolic disorders presenting in the neonatal time period.

Neonatal Seizures and Inborn Errors of Metabolism: An Update

“…The diagnosis is suggested by the odor of maple syrup or burnt sugar in cerumen at 24 to 48 hours of life or in urine during the latter part of the first week and is confirmed by detecting increased values of BCAAs and BCKAs in blood and urine (2,8). MRI scan may show brain edema affecting the myelinated white matter (cerebellar white matter, dorsal brainstem, cerebral peduncles, posterior limb of the internal capsule, and peri-Rolandic cerebral white matter), thalami, and globi pallidi [5]. Vasogenic edema due to blood-brain barrier disruption may occur in MSUD mainly related to water increase in the extracellular spaces and mostly evident during acute metabolic decompensation [13].…”

“…Abnormal tone and hypo/ areflexia, lethargy, poor sucking, muscular hypotonia, irritability and apnea may be evident although they can be found in more common acute neonatal disorders like sepsis, severe heart insufficiency or HIE [3]. The co-occurrence of metabolic acidosis, hypoglycemia, cardiac disorders and liver disease may be supportive features [5,6]. Seizures are mostly recurrent or configure status epilepticus lasting for hours to days, refractory to antiepileptic treatment [7].…”

“…Diagnosis can be strongly suggested by the typical "sweaty feet" odor of the patients'urines [6]. Seizures may occur within the course of acute metabolic decompensation or as a consequence of intracranial hemorrhages (subarachnoid, intra-or periventricular, cerebellar, and diffuse, petechial lesions in the white matter) that have been reported in IVA [5]. Hemorrhages may be the result of various factors such as CNS edema due to accumulation of abnormal organic acids, thrombocytopenia, coagulopathy secondary to associated liver disease, and as a complication of anticoagulation therapy during hemofiltration [5].…”

“…Seizures may complicate acute metabolic decompensation. Diffuse swelling may be present on MRI of neonatal onset MMA [5]. Imaging in neonatal MMA may also show swelling, while later imaging reveals volume loss, delay in myelin maturation, calcification of the basal ganglia, and focal necrosis of the globi pallidi [5].…”

“…Diagnosis can be quite difficult, thus, a high index of suspicion is required [4]. Notably, when epilepsy occurs in a patient with IEM is commonly associated to other neurological and extra-neurological symptoms , that may address appropriate laboratory and neuroimaging investigations [5]. Epilepsy occurring in newborn with IEM may be classified according to clinical or etiopathogenetical criteria.…”