Home > D. Systemic pathology > Genetic and developmental anomalies > Genetic metabolic diseases > multiple acyl-CoA dehydrogenation deficiency

multiple acyl-CoA dehydrogenation deficiency

MIM.231680

Friday 18 March 2005

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#