Medium-chain acyl-coenzyme A dehydrogenase deficiency

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Medium-chain acyl-coenzyme A dehydrogenase deficiency (MCAD)
Other namesCarnitine deficiency secondary to medium-chain acyl-CoA dehydrogenase deficiency,[1] MCAD deficiency or MCADD
This condition is inherited in an autosomal recessive manner.
SpecialtyEndocrinology Edit this on Wikidata

Medium-chain acyl-CoA dehydrogenase deficiency (MCAD deficiency or MCADD) is a disorder of

fatty acids into acetyl-CoA. The disorder is characterized by hypoglycemia and sudden death without timely intervention, most often brought on by periods of fasting
or vomiting.

Prior to expanded newborn screening, MCADD was an underdiagnosed cause of sudden death in infants. Individuals who have been identified prior to the onset of symptoms have an excellent prognosis.

MCADD is most prevalent in individuals of Northern European Caucasian descent, with an incidence of 1:4000 to 1:17,000 depending on the population. Treatment of MCADD is mainly preventive, by avoiding fasting and other situations where the body relies on fatty acid oxidation to supply energy.

Signs and symptoms

MCAD is one of the enzymes responsible for dehydrogenation of fatty acids as they cycle through the beta-oxidation spiral.

MCADD presents in early childhood with hypoketotic hypoglycemia and liver dysfunction, often preceded by extended periods of fasting or an infection with vomiting. Infants who are exclusively breast-fed may present in this manner shortly after birth, due to poor feeding. In some individuals the first manifestation of MCADD may be sudden death following a minor illness.[2] A number of individuals with MCADD may remain completely asymptomatic, provided they never encounter a situation that sufficiently stresses their metabolism.[2][3] With the advent of expanded newborn screening, some mothers have been identified with MCADD after their infants had positive newborn screens for low carnitine levels.[4]

The enzyme

caloric intake is reduced, and energy needs are increased.[citation needed
]

Genetics

MCADD is inherited in an

homozygous state in 80% of Caucasian individuals who presented clinically with MCADD and in 60% of the population identified by screening.[2]

An individual's genotype does not correlate well with their clinical phenotype for MCADD. The clinical presentation of an individual with MCADD depends not only on the presence of the mutations in the ACADM gene, but also on the presence of environmental or physiological stressors that require the body to depend on fatty acid oxidation for energy. Some mutations, identified through newborn screening programs and associated with higher residual enzyme activity have not been seen in individuals with clinical symptoms of MCADD. Despite this, treatment with fasting avoidance remains the norm for all those diagnosed with MCADD.[2]

Diagnosis

Clinically, MCADD or another fatty acid oxidation disorder is suspected in individuals who present with

seizures, coma and hypoketotic hypoglycemia, particularly if triggered by a minor illness. MCADD can also present with acute liver disease and hepatomegaly, which can lead to a misdiagnosis of Reye syndrome. In some individuals, the only manifestation of MCADD is sudden, unexplained death often preceded by a minor illness that would not usually be fatal.[3]

fibroblasts can also be used for diagnosis.[3]

In cases of sudden death where the preceding illness would not usually have been fatal, MCADD is often suspected. The

sudden infant death syndrome.[8][9]

Treatment

As with most other fatty acid oxidation disorders, individuals with MCADD need to avoid fasting for prolonged periods of time. During illnesses, they require careful management to stave off metabolic

cornstarch. Illnesses and other stresses can significantly reduce the fasting tolerance of affected individuals.[10]

Individuals with MCADD should have an "emergency letter" that allows medical staff who are unfamiliar with the patient and the condition to administer correct treatment properly in the event of acute decompensation. This letter should outline the steps needed to intervene in a crisis and have contact information for specialists familiar with the individual's care.[3]

Misdiagnosis issues

  • The MCADD disorder is commonly mistaken for
    Reye Syndrome
    is a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu.
  • Most cases of
    Reye Syndrome are associated with the use of Aspirin
    during these viral infections.

Prognosis

A 1994 study of the entire population of New South Wales (Australia) found 20 patients. Of these, 5 (25%) had died at or before 30 months of age. Of the survivors, 1 (5%) was severely disabled and the remainder had either suffered mild disability or were making normal progress in school.[11] A 2006 Dutch study followed 155 cases and found that 27 individuals (17%) had died at an early age. Of the survivors, 24 (19%) suffered from some degree of disability, of which most were mild. All the 18 patients diagnosed neonatally were alive at the time of the follow-up.[12]

Incidence

MCADD is most prevalent in individuals of Northern European Caucasian descent. The incidence in Northern Germany is 1:4000, currently the highest in the world. Northern Europe is also the origin of the common mutation in MCADD. For populations without origins in Northern Europe, the incidence is significantly lower, 1:51,000 in Japan and 1:700,000 in Taiwan. The common mutation has not been identified in MCADD cases identified in Asian populations.[3]

References

  1. ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Medium chain acyl CoA dehydrogenase deficiency". www.orpha.net. Retrieved 14 April 2019.{{cite web}}: CS1 maint: numeric names: authors list (link)
  2. ^
    ISBN 978-3-642-15719-6
    .
  3. ^
    PMID 20301597. {{cite journal}}: Cite journal requires |journal= (help
    )
  4. PMID 21354840
    .
  5. PMID 3054550
    .
  6. ^ "C8 Elevated + Lesser Elevations of C6 and C10" (PDF). American College of Medical Genetics. Retrieved 2012-06-09.
  7. PMID 11826276
    .
  8. PMID 1635678
    .
  9. PMID 10388343
    .
  10. S2CID 28507050
    .
  11. PMID 8017963
    .
  12. PMID 16737882
    .

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Medium-chain_acyl-coenzyme_A_dehydrogenase_deficiency&oldid=1192536695"