MEN (General Swiss-German Mennonite)

Inheritance: autosomal recessive
Genes: ACADM

Medium-chain acyl-CoA dehydrogenase deficiency
ACADM deficiency
MCAD deficiency
Apparent carnitine deficiency secondary to medium-chain acyl CoA dehydrogenase deficiency

Mental retardation
Lethargy
Coma
Hypoglycemia
Failure to thrive
Weakness
Sudden infant death
Liver failure

MCAD (Medium-Chain Acyl-CoA Dehydrogenase Deficiency)

Clinical Characteristics

General description (for patients): 

Affected individuals suffer from episodes of weakness and low blood sugar to the point of entering a coma.  Untreated, this can lead to brain damage and even death in young patients.  Electrolytes become severely unbalanced, especially after prolonged fasting.  Survivors may have developmental disabilities, chronic muscle weakness and failure to thrive sometimes leading to the misdiagnosis of cerebral palsy.  Breast feeding may be protective.  Some individuals have no symptoms.

Medical description:  

MCAD deficiency is a cause of severe, episodic hypoglycemia, sometimes following fasting and viral infections.  Profound lethargy and coma in infants are common.  Left untreated, this condition is fatal in many infants.  Most have their first episode of decompensation in the second year of life.  It is sometimes misdiagnosed as Reye’s syndrome and is a recognized cause of sudden infant death syndrome.   Survivors are left with developmental disabilities, chronic weakness and failure to thrive.  It can be reliably diagnosed by measuring hexanoylglycine and phenylpropionylglycine in the urine.  Carnitine deficiency is relative as a consequence of the MCAD deficiency which causes a reduction in the pool of free carnitine.  Newborns may have elevated plasma levels of 3-hydroxy fatty acids.  Some individuals remain asymptomatic throughout life.

Genetics:

This autosomal recessive disorder is caused by a mutation in the medium-chain acyl-CoA dehydrogenase gene (ACADM) on chromosome one (1p31).  This enzyme is one of three dehydrogenases that catalyze the intitial reaction in the beta-oxidation of fatty acids.  Multiple mutations have been found.  Both homozygous and compound heterozygous genotypes may cause disease with variable expressivity depending upon the specific mutations.  The common mutation (985A>G) has been reported in Mennonites in Kansas and  Pennsylvania together with possibly another [IVS4-30A>G] in Pennsylvania.  Other inborn errors of mitochondrial fatty acid beta-oxidation include long-chain (#201460), very long-chain (#201475), and short chain (#201470) acyl-CoA dehydrogenase deficiencies of which only the latter has been listed as occurring in plain people in Eastern Pennsylvania.

Treatment:

Prompt diagnosis with glucose supplementation is essential.  Fasting must be avoided.  Dietary supplementation with L-carnitine has been helpful in some patients.

Prognosis:

Depends upon the stage of discovery and treatment.  Untreated it can be fatal during childhood, even in infancy but others are asymptomatic throughout life.  Long term prognosis for those effectively treated may be good.

Ancillary treatments and support:

Avoidance of fasting and prompt treatment of viral illness is important.  Careful monitoring is essential.

Specialists and specialty centers:

Nutritionist, neurologist, pediatrician.

References:

Matsubara, Y., Narisawa, K., Miyabayashi, S., Tada, K., Coates, P.M., Bachmann, C., Elsas, L.J.II, Pollitt, R.J., Rhead, W.J., and Roe, C.R.:  Identification of a common mutation in patients with medium-chain acyl-CoA dehydrogenase deficiency. Biochem. Biophys. Res. Commun. 171: 498-505, 1990.   PubMed ID: 2393404

Iafilla, A.K., Thompson, R.J., Jr., and Roe, C.R.:  Medium-chain acyl-coenzyme A dehydrogenase deficiency: clinical course in 120 affected children.  J. Pediat. 124: 409-415, 1994.  PubMed ID: 8120710

Casey, J.L.:  MCAD deficiency in Holderman Mennonites in central Kansas.  Kans. Med. 93: 306-308, 1992.  PubMed ID: 1460814

Kelly, D.P., Hale, D.E., Rutledge, S.L., Ogden, M.L., Whelan, A.J., Zhang, Z., and Strauss, A.W.:  Molecular basis of inherited medium-chain acyl-CoA dehydrogenease deficiency causing sudden child death.  J. Inherit. Metab. Dis. 15: 171-180, 1992.  PubMed ID: 1356169

Resources:

All In This Together
MCAD Angel.com

Associated Graphics