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Loss of skills/regression

An under-appreciated aspect of mitochondrial disease is the autonomic dysfunction (Zelnik, 1996; Axelrod, 2006) which can impact life on a daily basis. Patients often have some dysregulation of temperature, in which the baseline body temperature often measures in the 96s and 97s and sometimes lower; temperatures can drop even lower during the night. Less often, temperature values at baseline run higher than normal. This is a particularly important piece of information when assessing a mitochondrial patient who is sick with infectious symptoms. An apparent "low-grade" temperature of 100°F may be dismissed by an unknowing pediatric practice as being insignificant. However, if the patient's baseline temperature runs at 96°, such an impression may represent a mistaken conclusion.

Autonomic issues include the following, and may present or worsen together with significant trigger factors such as heat or excessive activity, inadequate calorie or fluid intake, or with generalized fatigue:

  1. Vascular dysautonomia with lability in heart rate and blood pressure. This can occur with orthostatic changes in position, but symptoms can also occur following exercise or activity, in temperatures that are too extreme, or sometimes for no apparent reason at all. Associated symptoms can include dizziness or lightheadedness, syncope, palpitations or irregular heart rate, dyspnea, and anxiety.
  1. Heat and cold intolerance. Heat intolerance is not uncommon and may be associated with fatigue, lethargy, irritability, and usually flushing or blotching although some may display pallor or mottling. Cold intolerance is not as common a problem but can be associated with a worsening of fatigue or muscle pain. Some show color changes akin to Raynaud syndrome; in some cases, the color changes can be associated with pain or peeling of the skin.

This intolerance of temperature extremes resembles a "cold-blooded state" in which a person is dependent on a satisfactory ambient temperature to remain comfortable.

  1. Inappropriate sweating. Patients may not sweat even in hot weather (which contributes to heat intolerance). Instead their skin might only become "clammy." However, some of these patients might instead sweat in inappropriate settings - in cold temperatures or at night in comfortable conditions. Excessive sweating may be an important factor when considering a patient's fluid requirement.
  1. Skin temperature variability. Patients may complain of feeling very hot or very cold. This self-impression (like the patient's body temperature) may not correlate with the way their skin feels to the touch.
  1. Pallor, flushing or blotching, mottling of the skin. These changes can occur in association with temperature changes (heat or cold), activity, emotional distress, infection, and general fatigue; however, they can also occur spontaneously without any particular triggering factor. Raynaud syndrome-like changes may occur especially with temperature changes (usually cold), as well as erythromelalgia-like phenomena with the appearance on the fingers and hands of painful, red lesions that are hot to the touch. It is postulated that erythromelalgia may represent a feature of vasomotor instability (Davis, 2002).
  1. Autonomic issues of the gut and bladder. The gut and bladder can show evidence of dysfunction, with bowel dysmotility more common, manifesting with any combination of esophageal dysmotility, gastroesophageal reflux, delayed gastric emptying, and constipation. Symptoms include anorexia, early satiety, pain and distension after eating, and difficulty passing bowel movements even when the stools are soft in texture (though may be large in volume). Bladder dysfunction may be associated with urinary retention, incomplete emptying and "double-voiding," urgency and frequency, incontinence, and when severe, vesicoureteral reflux and/or urinary tract infections. These issues at least in part are due to autonomic dysregulation.

Assessment and Recommendations

Inadequate fluid intake, if persistent and significant, can result in dehydration and associated fatigue and/or malaise. However, patients with autonomic dysregulation are at risk for vascular dysautonomia, and may experience orthostatic changes in blood pressure and heart rate. An inadequate intake of fluids can result in dizziness or lightheadedness, syncope, and significant fatigue, and may be associated with chronic nausea and vomiting, as well as an increase in migraine frequency and severity.

Although most individuals can accommodate a suboptimal intake of liquid (by concentrating their urine appropriately), patients with vascular dysautonomia may show significant clinical symptoms unless they are able to take in their daily requirement, or more (fruits and vegetables count toward the total daily fluid volume). Gut dysmotility may impact a patient's ability to meet this requirement enterally. Intravenous fluids can provide an effective alternative though with a risk of complications.


Axelrod FB, Chelimsky G, Weese-Mayer DE. Pediatric autonomic disorders. Pediatrics 2006;118:309-21.

Davis MD, Sandroni P, Rooke T, Low P. Arch Derm 2002;139(10):1337-43.

Zelnik N, Axelrod FB, Leschinsky E, et al. Mitochondrial encephalomyopathies presenting with features of autonomic and visceral dysfunction. Pediatr Neurol 1996;14:251-4.

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