Brain magnetic resonance imaging findings and radiologic review of maple syrup urine disease: Report of three cases

Abstract

BACKGROUND Maple syrup urine disease (MSUD) is a rare autosomal-recessive disorder that affects branched-chain amino acid (BCAA) metabolism and is named after the distinctive sweet odor of affected infants’ urine. This disease is characterized by the accumulation of BCAAs and corresponding branched-chain ketoacids of leucine, isoleucine, and valine in the plasma, urine, and cerebrospinal fluid. However, the mechanisms of MSUD-induced brain damage remain poorly defined. The accumulation of BCAAs in the brain inhibits the activity of pyruvate dehydrogenase and α-ketoglutarate, disrupting the citric acid cycle and consequently impacting the synthesis of amino acids, causing cerebral edema and abnormal myelination. CASE SUMMARY We report three neonates admitted to our hospital with the classic subtype of MSUD. All three patients, with a transient normal period, presented with poor feeding, vomiting, poor weight gain, and increasing lethargy after birth. Laboratory testing revealed metabolic acidosis. The serum tandem mass spectrometry amino acid profile showed elevated plasma levels of BCAAs (leucine, isoleucine, and valine). Brain magnetic resonance imaging (MRI) presented abnormal signals mainly involving the globus pallidus, thalamus, internal capsule, brainstem, and cerebellar white matter, which represent the typical myelinated areas in normal full-term neonates. CONCLUSION In our patients, MRI showed typical features, in concordance with the available literature. Early detection and timely treatment are very helpful for the prognosis of MSUD patients. Therefore, we discuss the neuroimaging features of MSUD to enhance the knowledge of pediatricians about this disease.

The clinico‐radiological findings of MSUD in a group of Egyptian children: Contribution to early diagnosis and outcome

“…The main clinical findings in this study include poor feeding, poor activity, seizures, and disturbed conscious level. A common finding in almost children was positive consanguinity in 18 children (85.7%) and positive family history in 13 children (61.9%), which are consistent with the autosomal recessive mode of inherence that was reported in other studies (Blackburn et al, 2017;Chimbili et al, 2020;Jaradat et al, 2015;Li et al, 2021;O'Reilly et al, 2021;Patil et al, 2020;Yunus et al, 2012).…”

“…This was inconsistent with other literatures that discussed the radiological finding of classic subtype of MSUD patients, and reported similar findings, see Table 4. These findings represent demyelination and disrupted water content in the white matter (Li et al, 2021). The serum leucine/isoleucine at the time of diagnosis was elevated in all cases (mean 2085.5 μmol/L), and this was lower than the value reported from a study done by Yunus et al who reported the mean in Malaysian MSUD children to be 3037 μmol/L for the classic subtype (Yunus et al, 2012).…”

“…MRI brain imaging in MSUD patients (especially in classic subtype) has a characteristic hyperintensity particularly DW1 sequence in the first few weeks of life. It mainly involves the globus pallidus, thalamus, internal capsule, brainstem, and cerebellar white matter, which represent the typical myelinated areas in normal full‐term neonates (Li et al, 2021 ). In our study, all patients with acute onset showed involvement of wide range of brain parenchyma.…”

“…It occurs due to a deficiency in an enzyme complex [branched chain α‐keto acid dehydrogenase (BCKAD)] that results in defects in the catabolism of the branched chain amino acids (BCAAs): leucine, isoleucine, and valine. The accumulation of these BCAAs has a toxic effect on the brain cells (Chimbili et al, 2020 ), as they inhibit the activity of pyruvate dehydrogenase and α‐ketoglutarate, leading to interruption of the citric acid cycle and consequently affecting the synthesis of amino acids, causing cerebral edema and abnormal myelination (Li et al, 2021 ).…”

“…MRI brain findings in cases of classic MSUD are unique, in which characteristic patterns of edema occurs especially at diffusion‐weighted imaging, and so it provide a useful tool for early diagnosis (Li et al, 2021 ). The characteristic types of brain edema that can be seen with MSUD are intramyelinic edema (typical pattern) and vasogenic edema.…”