Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (443 page)

   Decreased copper in serum and liver; normal in RBCs; increased copper in amniotic fluid, cultured fibroblasts, and amniotic cells

   Decreased serum ceruloplasmin

   Other Considerations

Carrier status for the Menkes disease gene can usually be determined by examination of multiple hairs from scattered scalp sites for pili torti. Changes in the metaphyses of the long bones resemble scurvy. Ascorbic acid oxidase is copper dependent.

Suggested Reading

Moller LB, Bukrinsky JT, Molgaard A, et al. Identification and analysis of 21 novel disease-causing amino acid substitutions in the conserved part of ATP7A.
Hum Mutat.
2005;26:84–93.

PARKINSON’S DISEASE (PD)

MIM #168600

   Definition

Alpha-synuclein is a highly conserved and abundant protein in neurons, and aggregated alpha-synuclein proteins form brain lesions that are hallmarks of PD regardless of the patient’s genotype. Accumulation of alpha-synuclein, a major component of Lewy bodies, results in loss of dopaminergic neurons in the substantia nigra.

   Who Should Be Suspected?

Clinical manifestations of Parkinson’s include resting tremor, muscular rigidity, bradykinesia, and postural instability. Multiple combinations of genetic and/or environment causes can result in sporadic or late-onset Parkinson’s.

   Relevant Tests and Diagnostic Value

   There is a wide genetic heterogeneity in Parkinson disease (PD). Mutations in the LRRK2 gene (12q12) are the most common genetic component, while mutations in the SNCA gene (4q22.1) encoding alpha-synuclein are found in several families with a high prevalence of PD. Mutations in the Parkin gene (6q26) have been identified in cases of autosomal recessive juvenile PD (MIM #600116), and multiple additional genes have been implicated in cases of autosomal dominant or autosomal recessive PD.

   Sequence analysis of entire coding regions; targeted mutation analysis; deletion/insertion analysis.

   Gene dosage analysis of SNCA. FISH analysis.

   Many other diseases have parkinsonian motor features (“parkinsonism”), and accurate diagnosis may depend on the presence of Lewy bodies on pathologic examination.

   Individuals that carry a Gaucher disease mutation (GBA gene mutation) have an approximately fivefold increased risk of developing Parkinson’s disease.

Suggested Readings

Feany MB. New genetic insights into Parkinson’s disease.
New Eng J Med.
2004;351:1937–1940

Gandhi PN, Wang X, Zhu X, et al. The Roc domain of leucine-rich repeat kinase 2 is sufficient for interaction with microtubules.
J Neurosci Res.
2008;86:1711–1720.

Michael J. Fox Foundation for Parkinson’s Research. Available from:
https://www.michaeljfox.org/