multiple acyl-CoA dehydrogenation deficiency

Autosomal recessive metabolic disease causing a lipid accumulation in liver, heart, and renal tubular epithelium, tissues that use fatty acids as a primary source of energy.

Synopsis

 systemic anomalies

• neonatal acidosis
• "sweat-sock" odor
• hypoglycemia
• sweaty feet odor
• stale breath odor
• neonatal death frequent
• lipid accumulation in liver, heart, and renal tubular epithelium

 craniofacial anomalies

• facial dysmorphism
• macrocephaly
• cerebral pachygyria
• cerebral gliosis
• large anterior fontanel
• high forehead
• flat nasal bridge
• telecanthus
• cataract
• malformed ears

 cardiac anomalies

• cardiomyocytic steatosis

 hepatic anomalies

• hepatocytic steatosis
• hepatomegaly
• Hepatic periportal necrosis

 hypoplasia of pancreatic ductules
 thymic involution
 thymic atrophy
 hypoglycemic coma

 muscular anomalies

• lipid storage myopathy
• vacuolar myopathy with lipid accumulation

 pancreatic anomalies

• acute pancreatitis
• recurrent pancreatitis

 thoracic anomalies

• pulmonary hypoplasia (respiratory distress)
• pulmonary alveolar proteinosis (2082330)
• bilateral 13 ribs

 renal anomalies

• selective proximal tubular damage
• renal cortical cysts (glomerulocysts)
• renal multicystic dysplasia
• polycystic kidneys (renal cystic disease)
• renal medullary dysplasia
• tubular cell steatosis
• lipid accumulation in renal tubular epithelium

 genital defects

• hypospadias
• cryptorchidism

 cerebrospinal anomalies

• cerebral pachygyria
• agenesis of the cerebellar vermis
• hypoplastic temporal lobes
• immature brain with white matter gliosis
• symmetric warty dyplasia of cerebral cortex
• spongiosis and gliosis of the spinal cord (2082330)

 placenta anomalies (12007026)

• delayed maturation
  • large-for-gestational-age size
  • abundant immature intermediate villi with cellular syncytiotrophoblast
  • persistent villous cytotrophoblast
  • decreased syncytial knots

• immature intermediate villi showed exaggeration of lacunar interstitial spaces consistent with non-hydropic villous edema
• marked lipid accumulation within extravillous trophoblasts of placental septa and cell islands
• light lipid accumulation in fibroblasts of stem villi

Biology

 acidosis
 hypoglycemia
 hyperammonemia
 organic aciduria
 glutaric aciduria
 glutaric acidemia
 ethylmalonic aciduria
 glycosuria
 generalized aminoaciduria
 defective dehydrogenation of isovaleryl CoA and butyryl CoA
 electron transfer flavoprotein-ubiquinosepta and cell islands. Light lipid accumulation was also noted within fibroblasts of stem villi. These findings suggest that in glutaric acidemia type II, fatty acid oxidation could also ne oxidoreductase defect

Variants

 early-onset type II glutaric aciduria
 late-onset type II glutaric aciduria

Loci:

 4q32-qter
 15q23-q25
 19q13.3

References

 Slukvin II, Salamat MS, Chandra S. Morphologic studies of the placenta and autopsy findings in neonatal-onset glutaric acidemia type II. Pediatr Dev Pathol. 2002 May-Jun;5(3):315-21. PMID: 12007026

 Colevas AD, Edwards JL, Hruban RH, Mitchell GA, Valle D, Hutchins GM. Glutaric acidemia type II. Comparison of pathologic features in two infants. Arch Pathol Lab Med. 1988 Nov;112(11):1133-9. PMID: 3178428

 Mitchell G, Saudubray JM, Gubler MC, Habib R, Ogier H, Frezal J, Boue J. Congenital anomalies in glutaric aciduria type 2. J Pediatr. 1984 Jun;104(6):961-2. PMID: 6726538

 Kamiya M, Eimoto T, Kishimoto H, Tsudzuki T, Morishita H, Wada Y, Wakabayashi T, Hashimoto T, Goodman SI, Frerman FE, et al. Glutaric aciduria type II: autopsy study of a case with electron-transferring flavoprotein dehydrogenase deficiency. Pediatr Pathol. 1990;10(6):1007-19. PMID: 2082330

 McMillan TA, Gibson KM, Sweetman L, Meyers GS, Green R. Conservation of central nervous system glutaryl-coenzyme A dehydrogenase in fruit-eating bats with glutaric aciduria and deficient hepatic glutaryl-coenzyme A dehydrogenase. J Biol Chem. 1988 Nov 25;263(33):17258-61. PMID: 3182847

 Bernstein J, Chandra M, Creswell J, Kahn E, Malouf NN, McVicar M, Weinberg AG, Wybel RE. Renal-hepatic-pancreatic dysplasia: a syndrome reconsidered. Am J Med Genet. 1987 Feb;26(2):391-403. PMID: 3812591