Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a disorder that is inherited via the autosomal recessive inheritance pattern. The inborn inability to catabolize medium chain fatty acids usually causes an abnormal buildup of fat in the hepatic and cerebral regions, alongside a multitude of other sequelae.

The condition is primarily diagnosed during early childhood, although there have been some documented cases where diagnosis was delayed until adulthood [1] [2]. Patients may be asymptomatic, or experience various symptoms, ranging from vomiting to a comatose state and sudden death [3] [4]. The symptom mainly related to MCAD deficiency is that of hypoketotic hypoglycemia, which is responsible for an altered mental status, weakness, lethargy or coma in young children or infants. Jitteriness, irritability and epileptic activity may also be manifestations due to which parents seek medical help.

Cardiological abnormalities and related symptomatology have also been documented in cases of infants diagnosed with MCAD deficiency. Pulmonary hemorrhage, ventricular tachycardias and irregular sleep patterns are amongst the symptoms described [5] [6] [7] [8]. They are typically elicited during a fasting period within the day, or following a confirmed or suspected viral infection. Although no neurological findings are usually present, severe metabolic stress can lead to corresponding deficits [1] [9]. Furthermore, growth may be slightly hindered and the young patients affected by MCAD deficiency may present with tachypnea, somnolence and hepatomegaly; the latter is very frequently associated with the condition [10].

Patients who do not manifest symptoms in early life will usually present in adulthood with cephalalgia and vomiting.

• Sudden Infant Death Syndrome

  Title Frequency of Medium-Chain Acyl-CoA Dehydrogenase Deficiency G-985 Mutation in Sudden Infant Death Syndrome Abstract A small percentage of apparent sudden infant death syndrome (SIDS) victims may have an unsuspected metabolic disorder. [corescholar.libraries.wright.edu]

  It is characterized by hypoketotic hypoglycemia, hyperammonemia, seizure, coma, and sudden infant death syndrome-like illness. [ncbi.nlm.nih.gov]

• Fatigue

  On follow-up, a total of 44 patients reported fatigue (35%; 28/80), muscle pain (31%; 25/80), and/or reduced exercise tolerance (39%; 31/80). [ncbi.nlm.nih.gov]

  It has been reported presenting after a first episode of alcohol intoxication. [ 4 ] It very occasionally presents in adulthood with muscle weakness and fatigue. Survivors of acute episodes may have severe hypoglycaemia-induced brain damage. [patient.info]

  Survivors remain asymptomatic between episodes but may have delayed achievement of developmental milestones and are more likely to have reduced exercise tolerance, fatigue, myalgia, neuro-psychiatric symptoms, and weight gain 8. [ispub.com]

• Cerebral Palsy

  Long-term outcomes include developmental and behavioral disability, chronic muscle weakness, failure to thrive, cerebral palsy, and attention deficit disorder (ADD). [ncbi.nlm.nih.gov]

  […] mental retardation, cerebral palsy, or both attributable to the effects of MCADD. [nature.com]

• Turkish

  In addition, we show that MCADD appears to occur as frequently in Turkish newborns as in the native German population. [ncbi.nlm.nih.gov]

• Vomiting

  Patients who do not manifest symptoms in early life will usually present in adulthood with cephalalgia and vomiting. [symptoma.com]

  This case report describes a 30-year-old white man who, following a period of nausea and vomiting, was admitted to the hospital with sudden mental status deterioration followed rapidly by clinical deterioration and death. [ncbi.nlm.nih.gov]

  During periods of metabolic stress, affected individuals may develop hypoglycemia, lethargy, vomiting, seizures, and liver dysfunction.… Read More [britannica.com]

  […] medium-chain acyl-CoA dehydrogenase deficiency the most common fatty acid oxidation disorder, presenting as acute episodes triggered by prolonged fasting for more than 12-16 hours, with hypoglycemia, vomiting, and lethargy, which may progress to seizures [medical-dictionary.thefreedictionary.com]

• Nausea

  This case report describes a 30-year-old white man who, following a period of nausea and vomiting, was admitted to the hospital with sudden mental status deterioration followed rapidly by clinical deterioration and death. [ncbi.nlm.nih.gov]

  Symptoms in the mother may only include nausea, vomiting, and abdominal pain, but the underlying issues can be severely problematic and sometimes life-threatening to the mother and fetus if the fetus is not delivered as soon as possible. [counsyl.com]

  Postoperative nausea and vomiting can delay restarting of oral feeds and increase the risk of hypoglycemia. [ispub.com]

  […] believe they said there were clear droplets viewed on biopsy, and somehow I had thought they were referring to glycogen that is non-stained when used with PAS). 7) Know that carnitine acyl-transferase-I is in the cytosol; CAS-II is in the mitochondria. 8) Nausea [forums.studentdoctor.net]

• Failure to Thrive

  Long-term outcomes include developmental and behavioral disability, chronic muscle weakness, failure to thrive, cerebral palsy, and attention deficit disorder (ADD). [ncbi.nlm.nih.gov]

  MCADD is usually diagnosed in infancy or early childhood, when the affected individual presents with symptoms such as vomiting, low blood sugar, lack of energy, and failure to thrive. [nxgenmdx.com]

• Recurrent Vomiting

  Characteristic features of MCAD deficiency include: Reye-like syndrome (an acquired encephalopathy characterized by recurrent vomiting, agitation, and lethargy), fasting intolerance with vomiting, recurrent episodes of hypoglycemic coma, hypoketotic dicarboxylic [mayomedicallaboratories.com]

• Tachycardia

  Pulmonary hemorrhage, ventricular tachycardias and irregular sleep patterns are amongst the symptoms described. They are typically elicited during a fasting period within the day, or following a confirmed or suspected viral infection. [symptoma.com]

• Hepatomegaly

  When, inadvertently he was given medium-chain triglycerides for 2 days, the excretion of abnormal metabolites of medium-chain fatty acids increased and hepatomegaly became more pronounced. [ncbi.nlm.nih.gov]

  Hypoglycemia Lethargy or coma Metabolic acidosis Hypotonia Later symptoms include: hepatomegaly, Reye syndrome-like episodes (hepatic encephalopathy), seizures, and sudden death Family history of sudden death in siblings Referral: If signs are present [archildrens.org]

  Furthermore, growth may be slightly hindered and the young patients affected by MCAD deficiency may present with tachypnea, somnolence and hepatomegaly; the latter is very frequently associated with the condition. [symptoma.com]

• Altered Mental Status

  The symptom mainly related to MCAD deficiency is that of hypoketotic hypoglycemia, which is responsible for an altered mental status, weakness, lethargy or coma in young children or infants. [symptoma.com]

  At age 22 months altered mental status and variable hypo- and hyperglycemia were reported during hospital admission for hand/foot/mouth disease [ 24 ]. [bmcmedgenet.biomedcentral.com]

• Neonatal Hypotonia

  hypotonia, respiratory acidosis Treatment: Not established *Gene has been identified, and molecular basis has been elucidated. [merckmanuals.com]

The workup involved in the diagnosis of medium chain acyl-CoA dehydrogenase deficiency includes serum and urine laboratory testing and a liver biopsy, if deemed necessary. The first step is the medical history, which, for most of the patients is negative for the condition; this is due to the inheritance pattern of MCAD, the autosomal recessive pattern, which usually leads to no concurrent generations with the same medical condition.

Serum laboratory testing includes electrolytes, blood gasses, glucose and ammonia levels. Typical findings are diminished bicarbonate, an anion gap, slightly or moderately elevated ammonia levels and low blood glucose. In some cases, hypoglycemia-related symptomatology occurs before a measurable hypoglycemia has been established. During pregnancy, prenatal genetic testing renders a diagnosis feasible. Urine testing is carried out in order to eliminate the possibility of ketonuria and to evaluate the acylcarnitine excretion pattern alongside an organic acid profile. Residual enzymatic activity can also be measured, for prognostic and therapeutic reasons [11].

Finally, a liver biopsy may illustrate wide mitochondrial membranes, large-droplet steatosis and electron-dense mitochondrial matrices, which are indicative of a mitochondrial oxidative disorder but are not pathognomonic of MCAD deficiency.

• Hypoketotic Hypoglycemia

  It is characterized by hypoketotic hypoglycemia, hyperammonemia, seizure, coma, and sudden infant death syndrome-like illness. [ncbi.nlm.nih.gov]

  Clinical manifestations thus include fasting hypoglycemia, severe metabolic acidosis, and hyperammonemia. [merckmanuals.com]

  The symptom mainly related to MCAD deficiency is that of hypoketotic hypoglycemia, which is responsible for an altered mental status, weakness, lethargy or coma in young children or infants. [symptoma.com]

  Typically hypoketotic hypoglycemia, lethargy and vomiting are triggered by an infection, fasting or surgery. Some patients, however, can present with a progressive metabolic crisis despite ketosis and normal blood glucose. [orpha.net]

  The metabolic consequences are severe and include hypoketotic hypoglycemia leading to a Reye-like hepatic encephalopathy syndrome and sudden death. [dovepress.com]

• Fasting Hypoglycemia

  BACKGROUND: Impairments in gluconeogenesis have been implicated in the pathophysiology of fasting hypoglycemia in medium-chain acyl-CoA dehydrogenase deficiency. However, whole body glucose and fat metabolism have never been studied in vivo. [ncbi.nlm.nih.gov]

  Clinical manifestations thus include fasting hypoglycemia, severe metabolic acidosis, and hyperammonemia. [merckmanuals.com]

The patient died of liver failure after 4 months of valproate treatment. [ncbi.nlm.nih.gov]

The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment. [orpha.net]

TREATMENT Treatment for Medium Chain Acyl-CoA Dehydrogenase Deficiency involves avoidance of fasting. Individuals with the disorder require frequent food intake and often need high carbohydrate, low fat diets. [evolvegene.com]

Screening and treatment aim to prevent metabolic crises and allow children with MCADD to lead healthy lives. Treatment Open Treatment is started as early as possible and is usually life long. [newbornscreening.on.ca]

Treatment - Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) Treatment for MCAD deficiency is simple and allows for a good prognosis. Treatment consists of avoiding fasting for more than 2-6 hours in an infant. [checkorphan.org]

Prognosis The prognosis is excellent in diagnosed patients who avoid fasting and who are managed appropriately during an intercurrent illness/ metabolic crisis. The documents contained in this web site are presented for information purposes only. [orpha.net]

Prognosis - Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) * Prognosis is difficult, because of the broad clinical spectrum. * The majority of children do well, if appropriately treated. [checkorphan.org]

What Is the Prognosis for an Individual with Medium-Chain Acyl-CoA Dehydrogenase Deficiency? Early diagnosis and dietary management are crucial for the best outcome. [counsyl.com]

Neonatal screening for the disorder is now possible but it is not known whether this would alter the prognosis. OBJECTIVE: To investigate the outcome of MCAD deficiency after the diagnosis has been established. [ncbi.nlm.nih.gov]

Similar studies on the urine of two patients reported with Reye-like syndromes of unidentified etiology have suggested the retrospective diagnosis of medium-chain acyl-coA dehydrogenase deficiency. [ncbi.nlm.nih.gov]

We conclude that the specific MCAD deficiency mutation G-985 is not strongly associated with SIDS and that MCAD deficiency probably does not make a significant contribution to the etiology of SIDS. Repository Citation Miller, M. E., Brooks, J. [corescholar.libraries.wright.edu]

Etiology MCADD is caused by mutations in the ACADM gene (1p31) which encodes the mitochondrial MCAD protein. The most prevalent mutation, c.985A>G, (K329E), p. [orpha.net]

This article updates a human genome epidemiology review of MCADD published in 1999. The focus of this update is on epidemiologic parameters rather than mutations associated with MCADD. [ncbi.nlm.nih.gov]

Summary Epidemiology The estimated birth prevalence of MCADD is thought to range from 1/4,900 to 1/27,000 in Caucasian populations and is highest in individuals of Northern European descent. The worldwide birth prevalence is 1/14,600. [orpha.net]

Results suggest involvement of free radicals in the pathophysiology of MCAD deficiency. The underlying mechanisms behind the increased SOD activity upon carnitine supplementation need to be determined. [ncbi.nlm.nih.gov]

The pathophysiology of MCAD deficiency results from the inability to carry out the first step of beta-oxidation. [emedicine.com]

[email protected] 25 School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, 451 Smyth Rd, Ottawa, ON, K1H 8 M5, Canada. [email protected] 26 School of Epidemiology, Public Health and Preventive Medicine [ncbi.nlm.nih.gov]

Managing and preventing illness events explored parental experiences of managing illness events and their approach to preventing these events. [shura.shu.ac.uk]

Treatment involves: Frequent feeding, especially when ill To prevent a metabolic crisis, babies with MCADD must not go a long time without eating. [newbornscreening.on.ca]

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