Table A10.

MSUD Scoring.

Condition		Screening		Treatment
Severity	There is a rapidly progressing form The condition can be fatal by adolescence Classic MSUD: If untreated, progressive brain damage is inevitable and death occurs usually within weeks or months. (Rarediseases.org)	Availability	DBS test is available and in use	Availability	A therapeutic strategy is available (diet, HSCT, BMT) The treatment of classic, intermediate, intermittent, and thiamine-responsive MSUD has three chief components: 1. Lifelong therapy to maintain an acceptable diet; 2. Life-long maintenance of normal metabolic conditions including the levels of the BCAAs in the body; 3. immediate medical intervention for metabolic crises. (Rarediseases) Even if affected individuals follow the specialized diet strictly, the risk of metabolic crisis always remains. (Rarediseases)
Onset	Onset of classic MSUD (50–75% of cases) (Orphanet) occurs in the neonatal period, usually within the first 24–48 h of life. (https://www.ncbi.nlm.nih.gov/gtr/conditions/C0024776, accessed on 31 May 2021)	Performance	DBS test has a low false-positive rate or a high PPV [24]	Outcomes	The therapeutic strategy changes the prognosis for all forms of the condition Pre-symptomatic initiation results in better outcomes If identified prior to the development of symptoms, outcomes are generally better, with normal growth and development. (Rarediseases) Patients who present symptomatically can have significant neurologic sequelae including neurodevelopmental delay, especially if acidosis and hyperammonemia are severe. (Orphanet)
Frequency	Incidence/prevalence is≥1/150,000 and <1/100,000 Birth incidence is 0.74/100,000 (~1/137,000) [24]