What is GLUTARIC ACIDURIA II (MADD, ETF)?

rare autosomal recessive mutations in 3 different genes: ETFA (IIA), ETFB (IIB), ETFDH (IIC) 3 forms: 1) neonatal onset with congenital anomalies 2) neonatal onset without congenital anomalies 3) mild form, late onset Criteria to distinguish dicarboxylic aciduria originating from MCT feeding and other conditions are needed in urinary organic acid profiling for detecting inborn errors of metabolism [Tserng KY 1996] FLAD1 variants as a cause of potentially treatable inborn errors of metabolism manifesting with MADD [Olsen RKJ et al. 2016]

Gibt es eine deutsche Bezeichnung?

Glutarazidurie Typ 2; Multipler Acyl-CoA-Dehydrogenase-Mangel; MADD

Which enzymes are involved?

electron transfer flavoproteine (ETF), ETF-ubiquinone oxireductase, electron transfer flavoprotein dehydrogenase

GLUTARIC ACIDURIA II (MADD, ETF)

Disease	GLUTARIC ACIDURIA II (MADD, ETF)
Synonym	MULTIPLE ACYL-CoA DEHYDROGENASE DEFICIENCY; MADD
OMIM	231680 OMIM = Online Mendelian Inheritance of Men
Orphanet	26791
Protein (UniProt)	electron transfer flavoproteine (ETF), ETF-ubiquinone oxireductase, electron transfer flavoprotein dehydrogenase
ExPASy	1.5.5.1
Gene locus	15q24.2-q24.3, 19q13.41, 4q32.1
ICD	E71.3
Summary	rare autosomal recessive mutations in 3 different genes: ETFA (IIA), ETFB (IIB), ETFDH (IIC) 3 forms: 1) neonatal onset with congenital anomalies 2) neonatal onset without congenital anomalies 3) mild form, late onset Criteria to distinguish dicarboxylic aciduria originating from MCT feeding and other conditions are needed in urinary organic acid profiling for detecting inborn errors of metabolism [Tserng KY 1996] FLAD1 variants as a cause of potentially treatable inborn errors of metabolism manifesting with MADD [Olsen RKJ et al. 2016]
Laboratory findings	Adipic acid inc (urine) Ketone bodies (urine) inc (urine) Sebacic acid normal/inc (urine) Suberic acid inc (urine) Ethylmalonic acid inc (urine) Isovaleroylglycine inc (urine) 2-Methylbutyric Acid inc (urine) 2-Methylbutyrylglycine normal/inc (urine) 3-Hydroxyisovaleric acid inc (urine) 4-Hydroxybutyric acid inc (urine) 5-Hydroxyhexanoic acid inc (urine) Acylcarnitine (C2) inc (urine) Ammonia inc (blood) Butyryl/Isobutyrylcarnitine (C4) inc (blood) Butyrylglycine inc (plasma) Butyrylglycine inc (blood) Butyrylglycine inc (urine) Creatine kinase inc (plasma) D-Glucose dec (serum) Decanoylcarnitine (C10) inc (blood) Dicarboxylic acids inc (urine) Dodecanoylcarnitine (C12) inc (blood) Glutaric acid inc (urine) Glutarylcarnitine (C5DC) n/i (dried blood spot (DB) Hexanoylcarnitine (C6) inc (blood) Hexanoylcarnitine (C6) inc (urine) Hydroxyproline inc (urine) Isobutyric acid inc (urine) Isobutyrylglycine inc (urine) Isovaleric acid inc (urine) L-Lactic acid inc (urine) L-Lysine inc (urine) Octanoylcarnitine (C8) inc (blood) Palmitoylcarnitine (C16) inc (blood) pH normal/dec (blood) Proline inc (urine) Sarcosine normal/inc (urine) Tetradecanoylcarnitine (C14)/Propionylcarnitine (C3) inc (blood)
Symptoms	cardiomyopathy coma liver involvement or dysfunction rhabdomyolysis polycystic kidneys cardiomyopathy, hypertrophic episodic course (metabolic findings) hyperammonemia hypotonia liver, fatty metabolic acidosis multicystic dysplastic kidneys myopathy pericardial effusion vomiting Amino acids, plasma Amino acids, urine dysmorphism early death exercise intolerance feeding difficulties, poor feeding flat depressed nasal bridge (saddle nose) hepatomegaly (large liver) hypoglycemia hypospadia hypothermia intrauterine growth retardation lactic acidosis liver steatosis low set ears MRI, brain, abnormalities [-] MRI, brain, white matter abnormalities [-] MRS, brain, abnormalities muscle weakness neuropathy onset, adolescent onset, adulthood onset, childhood onset, infancy onset, neonatal Organic acids, urine pain, muscle pancreatitis polyhydramnion (maternal) prominent forehead renal cysts seizures small for gestational age (SGA), intrauterine growth retardation (IUGR)