Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (98 page)

Patients present early on with mental retardation, delayed development, extrapyramidal motor symptoms, and self-mutilating behavior and also severe gout and renal disorders. A genetic mutation is found in the hypoxanthine–guanine phosphoribosyltransferase enzyme gene and results in deficient enzymatic activity. A large number of mutations of this gene have been reported.
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   Laboratory Findings

Molecular genetic testing with sequence analysis of the entire coding region is available for Lesch-Nyhan syndrome as both a carrier test and prenatal test.

Reference

1.  Mak BS, Chi CS, Tsai CR, et al. New mutations of the HPRT gene in Lesch-Nyhan syndrome.
Pediatr Neurol.
2000;23:332.

ESSENTIAL TREMOR

   Definition

Essential tremor (ET) is defined as an isolated tremor with no other physiologic or psychological symptoms. It is common and may be seen in up to 5% of the population.
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   Clinical Presentation

Patients present with a tremor on exertion of the affected muscle group. Mental or physical stress may worsen the symptoms. Most common are tremors of the hands or arms, but the head, neck, jaw, and other body parts may be affected. There is a complex genetic inheritance of ET with a dominant form revealing linkage to genetic loci on chromosomes 2P, 3q13, and 6p23.
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In one study, neuropathologic changes noted in the brains of patients with ET at autopsy have revealed brain stem Lewy bodies and degenerative changes in the cerebellum.
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A separate study revealed loss of pigmented neurons in the locus ceruleus.
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   Laboratory Findings

Commercial genetic testing is not currently available for ET although this is a common form of motor disorder that should be distinguished from other progressive and treatable disorders such as Parkinson disease and metabolic disorders. Screening laboratory tests for thyroid disease (TSH and free T4), diabetes, and drug levels (sympathomimetic drugs and stimulants), caffeine, and alcohol may rule out causes for nonessential tremor.

References

1.  Louis ED, Ottman R, Hauser WA. How common is the most common adult movement disorder? Estimates of the prevalence of essential tremor throughout the world.
Mov Disord.
1998;13:5.

2.  Shatunov A, Sambuughin N, Jankovic J, et al. Genomewide scans in North American families reveal genetic linkage of essential tremor to a region on chromosome 6p23.
Brain.
2006;129:2318.

3.  Louis ED, Faust PL, Vonsattel JP, et al. Neuropathological changes in essential tremor: 33 cases compared with 21 controls.
Brain.
2007;130:3297.

4.  Shill HA, Adler CH, Sabbagh MN, et al. Pathologic findings in prospectively ascertained essential tremor subjects.
Neurology.
2008;70:1452.

RESTLESS LEG SYNDROME

   Definition

Restless leg syndrome (RLS) is a motor disorder in which patients feel the need to move their legs to alleviate discomfort. It may be primary or secondary. The primary, idiopathic form of this disorder is associated with a familial component in patients with onset before age 40. RLS has been shown to be associated with genetic variants of BTBD9 and MEIS1, both of which influence expression of the disorder and are involved in iron homeostasis.
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RLS may also be associated with a number of medical disorders including iron deficiency, renal disease, diabetes, multiple sclerosis, Parkinson disease, pregnancy, rheumatic disease, and venous insufficiency.

   Clinical Presentation

Patients present with an irresistible urge to move, most commonly when at rest or trying to sleep, because of unpleasant sensations in the legs of other body parts. The diagnosis of RLS is primarily made on clinical evaluation and history. Genetic testing is currently not commercially available. Underlying medical disorders that may be causative should be ruled out with appropriate testing.

References

1.  Winkelmann J, Schormair B, Lichtner P, et al. Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions.
Nat Genet.
2007;39:1000.

2.  O’Keeffe ST, Gavin K, Lavan JN. Iron status and restless legs syndrome in the elderly.
Age Ageing.
1994;23:200.

AMYOTROPHIC LATERAL SCLEROSIS (ALS)

   Definition

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that may be familial resulting in muscle weakness and death.

   Clinical Presentation

Patients with ALS present with upper and lower motor neuron dysfunction beginning in the cranial/bulbar, cervical, thoracic, or lumbosacral regions. There is steady progression of the disease over years, spreading to the other regions, resulting in weight loss and muscle wasting. Familial ALS accounts for 5–10% of all ALS cases (see eBook Figure 4-17).

Diagnosis is made on clinical history and examination. Sensory and motor nerve conduction studies and electromyography may help support the diagnosis when features of acute and chronic denervation and reinnervation are present. Neuroimaging may exclude other possible diagnoses.

   Laboratory Findings