Pyruvate decarboxylase deficiency
Overview
A rare genetic disorder involving an enzyme (pyruvate decarboxylase) deficiency which results in symptoms such as failure to thrive, psychomotor retardation, small head, eye problems, increased blood ammonia levels and lactic acidosis which can result in infant death in severe cases.
Symptoms
* Intermittent ataxia * Choreoathetosis * Carbohydrate intolerance * Failure to thrive * Sever psychomotor retardation * Blindness * Small head * Optic atrophy * Hypotonia * Reduced brain white matter * Reduced brain grey matter * Lactic acidosis * High ammonia blood level
Causes
* Orthopedic issues affecting the foot, ankle, leg, knee, or hip * Peripheral neuropathy (sensory and/or motor) –Slapping gait: Sensory neuropathies may result in a tendency to slap the feet firmly against the ground to improve proprioceptive input –Steppage gait: Seen in patients with foot drop –The classic tabetic gait combines both stepping and slapping gaits * Mononeuropathy/radiculopathy affecting the lower extremities may result in gait abnormalities (e.g., either a peroneal neuropathy or L5 radiculopathy can cause a unilateral steppage gait) o Myelopathy –Patients with bilateral lower extremity weakness and hypertonicity secondary to a spinal cord lesion may exhibit a spastic gait with stiffness of both legs and a tendency toward scissoring of the legs with walking o Brainstem or cortical lesions (e.g., multiple sclerosis, CVA) –Most commonly result in a hemiparetic gait with circumduction of the weak leg o Cerebellar lesions –Result in an ataxic gait, which tends to be wide-based, irregular, and staggering o Intoxications + Parkinsonism –Patients exhibit stooped posture, decreased arm swing, and shuffling (take many small steps) + Myopathies –Tend to produce a waddling gait because of weakness of the trunk, hip, and proximal lower extremity muscles + Spinocerebellar ataxia + Hereditary spastic paraparesis + Hysterical gaits + Inherited neuropathies (e.g., Charcot-Marie-Tooth disease) + GALOP syndrome (gait disorder, autoantibodies, late age onset, polyneuropathy) + Normal pressure hydrocephalus + Infection (e.g., neurosyphillis, meningitis) + Vitamin B12 or thiamine deficiency
Diagnosis
1. Is there vertigo, tinnitus, or deafness? Any one of these three signs and symptoms should suggest Ménière's disease or other labyrinthine disease as well as eighth nerve pathology. 2. Are there headaches, nystagmus, or papilledema? These signs should suggest a cerebellar tumor or acoustic neuroma. 3. Are there other neurologic signs? If there are long tract signs such as hyperactive reflexes and loss of vibratory or position sense, one should consider multiple sclerosis, pernicious anemia, or basilar artery insufficiency. If there are glove and stocking hypoesthesia and hypoactive reflexes, one should consider peripheral neuropathy or tabes dorsalis. 4. Is the ataxia worse in the dark? This is a sign that the dorsal column or peripheral nerve is affected, and one should look for peripheral neuropathy, pernicious anemia, multiple sclerosis, and Friedreich's ataxia. One should also look for tabes dorsalis. 5. Is there a secondary gain? Hysterical patients and patients who are malingering will often show a completely normal neurologic examination, but be unable to walk or stand without staggering. The author has been particularly impressed with patients applying for long-term disability who stagger a great deal without support, but as soon as support in the form of a cane is given, their ataxia completely clears up.
Treatment
* Specific symptomatic measures to improve gait stability and efficiency may improve functional abilities –Assistive devices (e.g., canes, walkers, wheelchairs) –Orthotics (e.g., ankle-foot orthoses for foot drop) –Physical therapy * Removing intoxicating substances if present * Orthopedic pathologies may be resolved by rest, casting or orthotics, NSAIDs, or surgical therapy * Peripheral neuropathy/mononeuropathy: Treat the underlying cause to improve gait or prevent worsening * Radiculopathy: Physical therapy, medications (e.g., NSAIDs, muscle relaxants), local injection therapies (e.g., epidural injections), and/or surgical intervention * Myelopathy: Treating the underlying cause may improve or prevent worsening of gait; spasticity may be treated with antispasticity agents (e.g., baclofen) * Structural lesions of the brainstem, cerebellum, or cerebrum should be identified and treated if possible (e.g., multiple sclerosis)