Adrenomyeloneuropathy Masquerading as Charcot-Marie-Tooth Disease

Figure 26-1 Pes cavus, right toe drop, wasting of intrinsic hand muscles, hyperpigmented scars and joint creases.



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Figure 26-2 Mucosal pigmentation, best seen at the side of the tongue.


Nerve conduction study reveals features of axonal degeneration and demyelination. For instance, the right ulnar compound muscle action potential (CMAP) is borderline reduced at 5.6 mV with normal forearm and across-elbow conduction velocities. However, the distal and F latencies are prolonged at 3.9 ms and 38.6 ms. The median nerve shows mild temporal dispersion at the forearm segment. Tibial and peroneal nerves are unexcitable. Sural sensory potential is absent. The ulnar orthodromic sensory nerve action potential (SNAP) at digit V is 4.1uV. A magnetic resonance imaging (MRI) scan of the brain does not show any white matter abnormalities. Serum cortisol does not rise during the short adrenocorticotropic hormone [ACTH] stimulation (Synacthen, Novartis, East Hanover, NJ) test: 111, 207, 211 nmol/L at 0, 30, and 60 minutes, respectively, after ACTH injection. Serum ACTH is raised at 19.6 pmol/L (normal < 10.2 pmol/L). Very long chain fatty acid analysis reveals increased C26:0, C24/C22 and C26/C22 ratios, confirming the diagnosis of adrenomyeloneuropathy.


He now takes hydrocortisone 10 mg in the morning and 5 mg every evening. He is also on testosterone injections. His distal limb weakness continues to worsen gradually. However, he is still fully functional and uses an ankle orthosis to improve his gait.




CONCLUSIONS


Adrenomyeloneuropathy (AMN) is a sex-linked recessive condition allelic to adenoleukodystrophy (ALD).1,2 It occurs as a result of various point mutations or deletions of the adrenoleukodystrophy protein (ALDP) gene at chromosome Xq28.3 The clinical features vary considerably, even within the same kindred. The spectrum ranges from childhood-onset ALD to adrenal insufficiency without neurologic involvement.1,2,4


AMN usually presents between the 2nd and 4th decade with spastic paraparesis and variable lower motor neuron and autonomic signs. The pathology in the peripheral nerves reflects mixed axonal neuropathy with superimposed demyelination and remyelination.1,5 Not unexpectedly nerve conduction study reveals features of primary axonal degeneration with superimposed multifocal demyelination.6 Cerebrospinal fluid (CSF) examination, except in advanced cases with overt cerebral involvement, is normal.1 A normal MRI scan, seen in about 50% of cases, correlates with intact cognition and a better prognosis.4,7 Adrenal insufficiency is present in about 70% of patients. Hypogonadism and low testosterone levels are also associated. The dysfunction of these organs is directly related to very long chain fatty acid accumulation.8 Treatment at present is geared primarily toward the endocrinopathy.


It is not difficult to understand why our patient’s clinical features were mistaken for CMT2. A recent study of 61 persons from 18 families with CMT2 confirmed that the typical phenotype is one of uniform, symmetric, distal weakness, atrophy, and sensory abnormalities. However, 16% had extensor plantar response and 23% had intact ankle reflex. Hyperreflexia and asymmetric weakness were present in some individuals (six patients had brisk ankle jerks).9 Charcot-Marie-Tooth disease type X (CMTX)10 is another inherited peripheral neuropathy that can mimic AMN. It shares with AMN the sex-linked inheritance, asymmetric neurological deficits and mixed axonal-demyelinating electrophysiology.


The consequences of not diagnosing AMN may be grave in view of the life-threatening complications associated with the adrenal insufficiency. Hyperpigmentation secondary to adrenal failure is difficult to appreciate in darkly pigmented races. A Synacthen test is a simple and inexpensive test. Hence, it is reasonable to consider screening for AMN with a Synacthen test in atypical cases of CMT2 and CMTX.

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Dec 16, 2016 | Posted by in NEUROLOGY | Comments Off on Adrenomyeloneuropathy Masquerading as Charcot-Marie-Tooth Disease

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