Maple Syrup Urine Disease Clinical Presentation

Updated: Nov 04, 2014
  • Author: Olaf A Bodamer, MD, PhD, FAAP, FACMG; Chief Editor: Luis O Rohena, MD, FAAP, FACMG  more...
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Classic maple syrup urine disease (MSUD) is the most common form, with symptoms developing in neonates aged 4-7 days, depending on feeding regimen. Breastfeeding may delay onset of symptoms to the second week of life. The initial symptoms typically include poor feeding, vomiting, poor weight gain, and increasing lethargy. In cases of non-classic MSUD, onset may be later and symptoms may vary.



The clinical presentation of a child with MSUD widely varies between patients. However, 5 distinct clinical phenotypes can be distinguished based on age of onset, severity of clinical symptoms, and response to thiamine treatment as part of a clinical spectrum. These clinical phenotypes are the classic, intermediate, intermittent, thiamine-responsive, and E3-deficient forms of MSUD. [6]

In classic MSUD, neurological signs (eg, alternating muscular hypotonia and hypertonia, dystonia, seizures, encephalopathy) rapidly develop. Signs of pseudotumor cerebri may be observed. Acute transient ataxia has been reported in well-controlled patients with classic MSUD. Pancreatitis has been occasionally reported. Ketosis and the characteristic odor of maple syrup in the urine are usually present when the first symptoms develop. However, otherwise healthy infants with the characteristic odor of MSUD have been reported. The reason for this observation is not known. [6, 9, 13, 14]

Intermediate MSUD is much more rare than classic MSUD; approximately 20 patients have been reported with this phenotype. Clinical signs in these patients include neurological impairment, developmental delay of varying degree, and seizures. Patients may present at any age, depending on residual BCKD activity, which ranges anywhere from 3-30% of the reference range. Episodes of acute metabolic decompensation are the exception.

Intermittent MSUD is the second most common form of MSUD. These patients develop with normal growth and intelligence. Patients with intermittent MSUD present during episodes of catabolic stress, including intercurrent illnesses (eg, otitis media). During these episodes, ataxia, lethargy, seizures, and coma may ensue. Patients with intermittent MSUD have died during these episodes when not appropriately treated.

Thiamine-responsive MSUD is a rare form of MSUD. Only the initial patient reported by Scriver et al has been shown to be unambiguously responsive to thiamine. [5] Since that patient's experience, other patients have been reported to show some improvement of metabolic control to thiamine in addition to dietary restriction of branched-chain amino acids. [5]

E3-deficient MSUD is a very rare form of MSUD, with fewer than 10 patients reported in the medical literature. The clinical presentation is almost indistinguishable from intermediate MSUD with the exception of accompanying lactic acidosis. These patients have combined deficiencies of BCKD, pyruvate, and alpha-ketoglutarate dehydrogenase complexes. [6]



See Pathophysiology.