Classification and goals - MSUD

MSUD is the result of deficiency of the multi-enzyme α-ketoacid dehydrogenase and symptoms can occur early after birth, and present prior to results of NBS tests are available. Rapid follow up of positive NBS reports should result in fewer infants showing severe clinical symptoms in the newborn period¹.

Several clinical forms of MSUD are known, differentiated by the amount of residual enzyme activity, age of onset, severity of the disorder and responsiveness to thiamine supplementation. Severe forms of MSUD, with less than 3% residual enzyme activity usually present as acute, overwhelming illness in the neonatal period if not detected by New Born Screening (NBS). Milder variants include the intermediate thiamin responsive, may be episodic and not become symptomatic until late childhood or even adult life^1,2.

Classical form	Poor feeding, vomiting, lethargy, ketoacidosis, seizures, sweet malty caramel like smell. Symptoms often present prior to availability of NBS results
Intermediate form	Failure to thrive, hypotonia, feeding problems, ketoacidosis and developmental delay
Intermittent form	Normal early development, episodic ataxia/ketoacidosis
Thiamin responsive form	Thiamin responsive: similar to intermediate phenotype

Suggested guidelines for blood branced amino acid concentrations in MSUD^,2,3,4,5
Amino acid µmol/l	Blau	Strauss et al 2009	GMDI consensus guideline 2015	Calcar et al 2015	Normal reference range
Leucine	100-300	100-300	> 5 years of age: 100-200 < 5 years of age: 100-300	100-300	65-200
Valine	200-400	200-400	200-400	200-400	90-300
isoleucine	150-300	200-400	200-400	100-300	26-100

These recommendations are only a guide and must be individualized for each patient, based on the severity of their disorder, actual needs, and blood quantitative amino acid levels.

References:

Dixon M, Macdonald A, White F. Disorders of amino acid metabolism, organic acidae,mias and Urea cycle disorders. In; Shaw V (ed) Clinical paediatric dietetics, 4^th John Wiley & Sons ltd. Sussex, 2015:381-526
Knerr I, Vockley J, Gibson KM. Disorders of leucine, isoleucine and valine metabolism. In; Blau N (ed) Physician’s guide to the diagnosis, treatment and follow-up of inherited metabolic diseases, 2^nd Springer Heidelberg, 2014103-142
Strauss KA, Wardley B. Classical maple syrup disease and brain development: principles of management and formula design. Mol Genet Metab 2010;99:333-345
Marriage B. Nutrtional management of patients with inherited disorders of brached-chain amino acid metabolism. In: Acosta PB (ed) Nutritional management of patients with inherited metabolic disorders, 1^st edn. Jones and Bartlett, Sudbury 2010:175-236
Calcar van S. Nutrition Management of Maple Syrup Urine Disease. In: Bernstein L.E. et al (eds), Nutrition Management of Inherited Metabolic Diseases, Springer International Publishing Switzerland 2015