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Summary
GLUTARIC ACIDURIA II (MADD)
MULTIPLE ACYL-CoA DEHYDROGENASE DEFICIENCY MADD
231680
OMIM = Online Medalian Inheritance of Men
26791
15q24.2-q24.3, 19q13.41, 4q32.1
  • high-carbohydrate diet
  • low-fat diet
  • riboflavin
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]
symptoms
Amino acids, plasma
Amino acids, urine
cardiomyopathy
cardiomyopathy, hypertrophic
coma
dysmorphism
early death
exercise intolerance
hyperammonemia
hypoglycemia
hypospadia
hypothermia
hypotonia
liver involvement or dysfunction
liver, fatty
low set ears
metabolic acidosis
muscle weakness
myopathy
neuropathy
onset, adolescent
onset, adulthood
onset, infancy
onset, neonatal
Organic acids, urine
pancreatitis
pericardial effusion
polyhydramnion (maternal)
renal cysts
rhabdomyolysis
small for gestational age (SGA), intrauterine growth retardation (IUGR)
sweaty feet odor
laboratory finding
Isovalerylglycine2.001000.000.200.90mmol/mol creatinineurine
Ammonia150.00350.0025.0080.00-Ámol/lblood
3-Hydroxyisovaleric acid50.00500.000.0046.00mmol/mol creatinineurine
2-Hydroxyglutaric acid (L)50.004300.001.0019.00mmol/mol creatinineurine
4-Hydroxybutyric acid130.007600.000.002.00mmol/mol creatinineurine
Ethylmalonic acid180.001150.00 mmol/mol creatinineurineno data
D-Glucose0.503.002.805.00mmol/lserum
Glutaric acid500.0012000.000.703.60mmol/mol creatinineurineadult
pH7.007.407.357.45no unitblood
Isobutyrylglycine0.00200.001.004.00mmol/mol creatinineurine
2-Methylbutyrylglycine2.00200.000.000.00mmol/mol creatinineurinechild
5-Hydroxyhexanoic acid 0.007.00increasedurine
Adipic acid35.001600.001.007.00mmol/mol creatinineurinechildhood 4-6y
Suberic acid2.00200.000.002.00mmol/mol creatinineurinechildhood
Sebacic acid0.000.000.002.00normal-increasedurinechild
Proline 0.00129.00increasedurine
Hydroxyproline0.000.0020.00320.00increasedurinenewborn
MRS, brain, abnormalities -
MRI, brain, abnormalities -
Acylcarnitine0.000.00 increasedurineno data
Butyryl/Isobutyrylcarnitine (C4) increasedblood
Decanoylcarnitine (C10) increasedblood
Dodecanoylcarnitine (C12) increasedblood
Tetradecanoylcarnitine (C14) increasedblood
Palmitoylcarnitine (C16) increasedblood
L-Lactic acid0.000.00 increasedurineno data
Isovaleric acid0.000.00 increasedurineno data
L-Lysine0.000.00 increasedurineno data
Sarcosine0.000.00 normal-increasedurineno data
2-Methylbutyric Acid0.000.00 increasedurineno data
Isobutyric acid0.000.00 increasedurineno data
Creatine kinase increasedplasma
Literature
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