Sleep induced abnormal motor behaviors caused by medium-chain acyl-CoA dehydrogenase deficiency: A case report☆
Article Outline
- 1. Introduction
- 2. Case description
- 3. Discussion
- Conflicts of interest
- Acknowledgement
- Appendix A. Supplementary data
- References
- Copyright
Keywords: Sleep, MCADD, Abnormal motor behaviors, Video-polysomnography, Video-electroencephalography, Fatty metabolism
1. Introduction
Inherited medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a severe, sometimes fatal autosomal recessive disorder, which can cause mitochondrial fatty β-oxidation disorder. The symptoms for MCADD are non-specific, including feeding difficulty, lethargy, vomiting, tachypnea or respiratory arrest, hypotonia, hypoglycemia, metabolic acidosis, coma, encephalopathy, seizures, sudden and unexpected death, and Reye-like syndrome [1], [2], [3], [4].
However, the symptom of sleep abnormality has not been reported until now. Here we present the case of a patient whose chief complaint was sleep-induced paroxysmal motor behaviors during non-REM sleep, which is a rare phenomenon in other sleep disorders.
2. Case description
We report an 18-year-old girl with normal developmental milestones who suffered from paroxysmal motor behaviors induced by sleep during both the day and night. However, she was normal when awake.
Her abnormal motor behaviors during sleep first occurred when she was four
months old and were characterized by trunk vermicular movements lasting several minutes per night. As she grew these episodes became more and more intensive, frequent, and complicated. At present, the patient exhibits various episodic manifestations, such as uttered guttural sounds, trunk torsion, turning over or vermicular movement, choreic limb movements, and leg treading or shaking movements during sleep (see video “episode recorded in hospital” and “episode recorded at home”). Occasionally, she would sit up or fall out of bed during sleep. All the episodes could be disturbed by waking her (see video “episode recorded in hospital-part 2” and Supplementary Fig. B). These episodes occurred several dozen times per night, occupying nearly the entire night, and the duration of each episode was from a few seconds to 40min.
Neurological examination, wake and sleep EEGs, interictal MEG, and brain magnetic resonance imaging were normal, but deep tendon reflexes of lower limbs were 3+ and bilateral ankle clonus were positive. Her family history was normal.
Psychometric evaluation showed a borderline mental level (Wechsler Adult Intelligence Scale: Full scale IQ 83, verbal IQ 88, performance IQ 78). The initial treatment with Carbamazepine (70mg/kgd) was ineffective, as were the treatments with Valproic, Clonazepam, Trihexyphenidyl, and Dopamine.
Blood organic acid analysis by tandem mass spectrometry (MS) showed several-fold increased values of C8 and C10 (C8: 0.87, normal range 0.04–0.2; C10: 0.97, normal range 0.04–0.35), and Urinary gas chromatographic mass spectrometric analysis showed that Ethylmalonic acid-2 was increased dramatically (14.35, normal range 0–6.2), which indicated that fatty acid metabolism was abnormal.
DNA analysis by PCR amplification of the exons of MCAD (result comparing to the ACADM reference sequence [NCBI Reference Sequence: NM_001127328.1]) revealed a single nucleotide mutation of 2586 T>Y.
Video-electroencephalography showed that the episodes happened during stage II of NREM sleep, the motor episodes of the patient did not interrupt NREM sleep and the main symptoms were intermittent trunk torsion and twisting combined with irregular limbs choreic movement (see video “episode recorded in hospital-part 1” and Fig. 1). There was no hypoxemia event during episodes (see Supplementary Figs. A and B).
Fig. 1.
Polysomnographic recording of an episode of the patient (the upper picture) showing that this episode happened in stage II of non-REM sleep with intermittent trunk rolling combining with irregular limbs movement.
The patient was treated with diet therapy (low fat diet, high glucose, and high protein diet), oral carnitine, Vit B2 and Vit B12 supplementation, and intravenous glucose and Coenzyme complex infusion. Her clinical symptoms were improved gradually. After a one-week treatment, the motor activity became less frequent and pronounced.
3. Discussion
We diagnosed MCADD based mainly on the result of blood test, gene mutation, and urine organic acid analysis and the effect of therapy. The increased deep tendon reflex and positive ankle clonus indicated impairment of the upper motor neurons. It was difficult to differentiate the episodes of our patient from nocturnal paroxysmal dystonia (NPD) and nocturnal frontal lobe epilepsy (NFLE), which are characterized by complex, bizarre motor patterns. NPD was recognized to be a manifestation of NFLE beginning as paroxysmal arousal and lasting less than twomin [5], [6]. However, several factors could suggest non-epileptic episodes, including the long-lasting attacks, wide spectrum of abnormal motor activity without a stereotypical pattern and without arousal at the episodic onset, negative EEG and MEG findings and resistance to Carbamazepine. Additionally, this abnormal motor activity could be disturbed and stopped either at the onset or during an episode.
Our case highlights the need for health care professionals to be aware of this uncommon manifestation of MCADD. Early diagnosis and prompt initiation of treatment appear to be effective in improving clinical symptoms and life quality of patients. In addition, we wonder why the abnormality of fatty metabolism influences sleep exclusively and what the mechanism of this influence is. In order to stimulate the discussion of these issues by medical doctors and researchers, we have provided a video documenting the case presented in this paper.
Conflicts of interest
The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest associated with this article can be viewed by clicking on the following link: doi:10.1016/j.sleep.2011.04.017.
Conflicts of Interest. ICMJE Form for Disclosure of Potential Conflicts of Interest form.
Acknowledgement
This study was supported by the National Natural Science Foundation of China (30800366).
Appendix A. Supplementary data
Supplementary data 2.
Supplementary video 3. Video “episode recorded in hospital”: including two parts. The video “episode in hospital 1” recorded during her sleep shown that the main episodic manifestations of the patient were trunk twisting and the lower limbs treading. The EEG combined with the video shown that the episodes happened during stage II of NREM sleep, the motor episodes of the patient did not interrupt NREM sleep. We could see the spindles and slow waves appearing before, during and after episodes clearly. The video “Episode in hospital 2” shown that the patient was recumbent on the right side and her main episodic manifestations were trunk torsion, twisting, lower limbs treading, shaking and circling in the air and position changing. We woke her up by patting her during episode and stopped her attack. Because there was something wrong with the microphone when her doing PSG, we couldn’t hear her guttural sounds. The PSG combined with it was shown in the supplement of Fig. B.
Supplementary video 4. Video “episode recorded at home”: it including 3 videos shown that the episodes happened during sleep were associated with various complex motor behaviors with uttering guttural sounds mainly including trunk torsion, shaking and turning over, limbs choreic movement, legs treading and circling in the air and position changing.
Supplementary data 5.
Supplementary data 6.
References
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- . So doctor, what exactly is wrong with my muscles? Glutaric aciduria type II presenting in a teenager. Neuromuscul Disord. 2006;16:269–273
- . From nocturnal paroxysmal dystonia to nocturnal frontal lobe epilepsy. Clin Neurophysiol. 2000;111(Suppl. 2):2–8
- . Paroxysmal motor disorders of sleep: The clinical spectrum and differentiation from epilepsy. Epilepsia. 2006;47:1775–1791
☆ The patient and her family have agreed with this report.
PII: S1389-9457(11)00303-0
doi:10.1016/j.sleep.2011.04.017
© 2011 Elsevier B.V. All rights reserved.
