Clint Kimble <kimble@...> Wrote:

I> have a 20 month old foster daughter who has recently been diagnosed
with
>MCAD. Does anyone have any information or advice for this condition.
>Thank You,
>Sheila

A search of www.alltheweb.com for "MCAD deficiency" showed 147 hits.
One of these is shown here. I hope you find it useful.
Good luck!


From:
http://www.pedianet.com/news/illness/disease/files/mcaddefi.htm


MCAD DEFICIENCY
DEFINITION:
A disorder of lipid metabolism characterized by a defect in the
oxidation of medium-chain fatty acids resulting in recurrent episodes of
hypoglycemia, vomiting, and coma when stressed.
EPIDEMIOLOGY:
incidence: 1/13,000-20,000 (most common fatty acid oxidation defect)
age of onset:
6 months to 2 years (mean = 11 months)
risk factors:
familial - autosomal recessive
chrom. #: 1p31
gene: medium-chain acyl-CoA dehydrogenase (MCAD)
Northwestern Europe
PATHOGENESIS:
1. Background
MCAD is one of four enzymes in the mitochrondria responsible for the
breakdown of medium-chain (C4-C14) fatty acids to 2-carbon fragments
(acetyl-CoA) in the beta oxidation pathway
there are 3 straight-chain acyl-CoA dehydrogenases to deal with long,
medium, and short chain fatty acids
2. History
1982 - Kolvraa et al.
first to recognize MCAD Deficiency
1986 - Matsubara et al.
assigned MCAD to chrom. 1p31
1987 - Kelly et al.
MCAD cDNA clone sequenced
1990 - Matsubara et al.
first point mutation identified: G985 (Lys -> Glutamine)
accounts for 85-90% of the mutant MCAD alleles
incidence of the G985 allele is about 1/70
3. Genetic Defect
genetic defect -> deficiency of MCAD activity -> homozygous patients are
unable to mobilize large fat stores and are thus at risk for becoming
hypoglycemic when stressed (i.e., during infection or fasting) during
which time the long and short acyl-CoA dehydrogenases are unable to
compensate for the lack of MCAD
may present as recurrent episodes of hypoglycemic coma with medium-chain
dicarboxylicaciduria, impaired ketogenesis (hypo-ketotic), and low
plasma & tissue carnitine levels
characterized by an intolerance to prolonged fasting
the patient may remain asymptomatic and appear healthy for long periods
of time but then present suddenly and fatally as a SIDS-like illness
MCAD Deficient patients may present with a family history of
SIDS or Reye's Syndrome
CLINICAL FEATURES:
1. Episodic Manifestations
the first episode usually occurs between .5 to 2 years of age after a
12-16 hour period of stress
1. Neurological Manifestations
lethargy -> coma
seizures occasionally
2. Gastrointestinal Manifestations
persistent vomiting ( dehydration)
hepatomegaly
INVESTIGATIONS:
1. Serum
wide anion gap metabolic acidosis (anion = dicarboxylic acid)
hypoketotic hypoglycemia
secondary hyperammonemia
elevated urea, uric acid, transaminases
prolonged PT, PTT
secondary carnitine deficiency (25% decline in level)
2. Urine
1. Organic Acids
low ketones
elevated medium-chain dicarboxylic acids
presence of glycine conjugates, octanoyl-carnitine, or hexonoic &
phenylpropionic acid in urine (after carnitine or phenylpropionylglycine
loading)
3. Diagnosis
deficiency of MCAD activity in leukocytes and cultured skin fibroblasts
prenatal
deficiency of MCAD activity in cultured chorionic villi or amniocytes
point mutations identified by PCR
4. Pathology
1. Liver
elevated neutral lipid deposits in either a micro- or macrovesicular
pattern
MANAGEMENT:
1. Supportive
a chronic disease with a life-long risk of episodes of hypoketotic
hypoglycemia and thus must:
provide long-term follow-up
moniter serum glucose (for hypoglycemia)
coordinate a multidisciplinary approach:
Paediatrics, Neurology, Dietary, Genetics, Metabolics
plan for acute episodes
provide a medic alert bracelet
2. Goals of Therapy
symptomatic control of and avoidance of acute episodes (stress)
not curative
3. Diet
1. Acute Episodes
glucose monitering with carbohydrate and high caloric supplements during
acute illness; frequent feeds - IV D10W (to suppress lipolysis) if
hospitalized
2. Chronic Management
ensure patients never fast for more than 10-12 hours
dietary fat restriction (low-fat)
breast-feeding may be preventative
4. Carnitine Therapy
100 mg/kg/day po
acts to eliminate potentially toxic metabolites which may accumulate
5. Prognosis
life threatening and up to 25% die during the first attack
excellent if patient survives initial episodes

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Source: Pedibase by Dr. Al Gandy (MD.,Phd.,FRCP(c))