Could there be a form of this that is inherited by a dominant mode? Linda S.

-----Original Message-----
From: emtech-journey <emtech-journey@...>
To: iem-family@onelist.com <iem-family@onelist.com>
Date: Thursday, September 09, 1999 6:49 AM
Subject: [iem-family] MCAD deficiency info


>From: emtech-journey <emtech-journey@...>
>
> 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
>
>Return to Index
>---------------------------------------------------------------------------
-----
>
>Source: Pedibase by Dr. Al Gandy (MD.,Phd.,FRCP(c))
>
>
>
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