MAPLE SYRUP URINE DISEASE (MSUD)

Question 1

What is  MAPLE SYRUP URINE DISEASE (MSUD)?

Accepted Answer

rare (1:200000 in Germany - 1:185000 world wide)
autosomal recessive (homozygous or compound)
4 different types:
(1) classic form
(2) intermittent form (normal between atacks)
(3) intermediate form
(4) Thiamine-responsive

(5) Dihydrolipoyl dehydrogenase (E3)-deficient

mutation in at least 3 genes: BCKDHA, BCKDHB, DBT

In MS/MS newborn screening, the mass spectrum of hydroxyproline cannot be differentiated from isoleucine and leucine causing false positive newborn screening test results for maple syrup urine disease (MSUD) [Staufner et al. 2016]

Question 2

Gibt es eine deutsche Bezeichnung?

Accepted Answer

Ahornsirup-Krankheit; Verzweigtketten-Ketosäuredecarboxylase-Mangel; MSUD

Question 3

What is the link to OMIM ?

Accepted Answer

OMIN 248600

Question 4

Which enzymes are involved?

Accepted Answer

Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial; 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial;2-oxoisovalerate dehydrogenase subunit beta, mitochondrial

Disease	MAPLE SYRUP URINE DISEASE (MSUD)
Synonym	BRANCHED-CHAIN ALPHA-KETO ACID DEHYDROGENASE DEFICIENCY (MSUD)
OMIM	248600 OMIM = Online Mendelian Inheritance of Men
Orphanet	511
Protein (UniProt)	Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial; 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial;2-oxoisovalerate dehydrogenase subunit beta, mitochondrial
ExPASy	1.2.4.4
Gene locus	1p21.2, 6q14.1, 19q13.2
ICD	E71.0
Summary	rare (1:200000 in Germany - 1:185000 world wide) autosomal recessive (homozygous or compound) 4 different types: (1) classic form (2) intermittent form (normal between atacks) (3) intermediate form (4) Thiamine-responsive (5) Dihydrolipoyl dehydrogenase (E3)-deficient mutation in at least 3 genes: BCKDHA, BCKDHB, DBT In MS/MS newborn screening, the mass spectrum of hydroxyproline cannot be differentiated from isoleucine and leucine causing false positive newborn screening test results for maple syrup urine disease (MSUD) [Staufner et al. 2016]
Laboratory findings	2-Hydroxyisovaleric acid inc (urine) allo-Isoleucine inc (urine) Leucine inc (urine) 2-Hydroxyisocaproic acid inc (urine) 2-Oxoisocaproic acid inc (urine) 2-Hydroxy-3-methylvaleric acid inc (urine) 2-Oxoisovaleric acid inc (urine) 3-Hydroxybutyric acid inc (urine) 3-Methyl-2-oxovaleric acid inc (urine) allo-Isoleucine inc (plasma) BCKAD complex dec (fibroblasts) D-Glucose dec (serum) Ferric chloride reaction (urine) Ketone bodies (urine) inc (urine) L-Isoleucine inc (plasma) L-Isoleucine inc (urine) L-Lactic acid normal/inc (urine) Leucine inc (plasma) pH normal/dec (blood) Valine inc (urine) Valine inc (plasma)
Symptoms	coma feeding difficulties, poor feeding ketosis, ketoacidosis unusual odor / odour vomiting maple sirup or caramel odor ataxia behavior, anxiety cerebral edema early death encephalopathy hypertonia, spasticity hypoglycemia irritability lethargy, drowsiness, apathy mental retardation metabolic acidosis pancreatitis papilloedema psychomotor retardation screaming or crying, abnormal seizures white matter changes, abnormalities apnea behavior, autism or autistic-like EEG abnormalities [-] Encephalopathic crisis, acute episodic course (clinical symptoms) hypotonia motor retardation MRI, brain, white matter abnormalities [-] myopathy onset, adolescent onset, childhood onset, infancy onset, neonatal ophthalmoplegia opisthotonus skoliosis, kyphoskoliosis