Sorted By Test Name - Mayo Medical Laboratories

NIEM
9313
Clinical Information: Niemann-Pick disease (types A and B) is a lysosomal storage disease caused
by a deficiency of the enzyme acid sphingomyelinase. The clinical presentation of type A disease is
characterized by jaundice, progressive loss of motor skills, feeding difficulties, learning disabilities, and
hepatosplenomegaly. Death usually occurs by age 3. Type B disease is milder, though variable in its
clinical presentation. Most type B patients do not have neurologic involvement and survive to adulthood.
Mutations in the SMPD1 gene are known to cause Niemann-Pick disease types A and B. The carrier rate
for Niemann-pick type A in the Ashkenazi Jewish population is 1/90. There are 3 common mutations in
the Ashkenazi Jewish population: L302P, R496L, and fsP330. The carrier detection rate for
Niemann-Pick type A with these 3 mutations using this assay is approximately 97%. The deltaR608
mutation accounts for approximately 90% of the type B mutant alleles in individuals from the Maghreb
region of North Africa and 100% of the mutation alleles in Gran Canaria Island.
Useful For: Carrier testing for individuals of Ashkenazi Jewish ancestry Prenatal diagnosis for at-risk
pregnancies Confirmation of suspected clinical diagnosis of Niemann-Pick disease types A and B in
individuals of Ashkenazi Jewish ancestry
Interpretation: An interpretive report will be provided.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Gross SJ, Pletcher BA, Monaghan KG: Carrier screening in individuals of
Ashkenazi Jewish descent. Genet Med 2008 Jan;10(1):54-56 2. Schuchman EH: The pathogenesis and
treatment of acid sphingomyelinase-deficient Niemann-Pick disease. J Inherit Metab Dis 2007
Oct;30(5):654-663
Niemann-Pick Type C Detection, Fibroblasts
Clinical Information: Niemann-Pick disease type C (NPC) is an autosomal recessive lysosomal
storage disorder caused by a defect in cellular cholesterol trafficking due to mutations in either the NPC1
or NPC2 gene. The resulting accumulation of unesterified cholesterol in late endosomes/lysosomes
interrupts the normal functioning of cells, tissues and organs. There are two other forms of Niemann-Pick
disease, types A and B, resulting from a deficiency of sphingomyelinase and mutations in the SMPD1
gene. Clinical features of NPC vary widely depending on the age of onset, which can range from the
neonatal period to adulthood. Most cases present in middle to late childhood with a classic disease course.
Hepatosplenomegaly may be the initial symptom of the disease. Clinical manifestations include vertical
gaze palsy, ataxia, dystonia, behavioral problems and dementia. In early onset cases, severe, lethal
neonatal liver disease and hydrops fetalis can occur. Common features of adult onset NPC include
psychiatric illness, ataxia, dystonia and speech difficulties. Currently, treatment and management are
supportive only. The diagnosis of NPC is confirmed by biochemical testing that demonstrates impaired
cholesterol esterification and positive filipin staining in cultured fibroblasts. About 90% of individuals
with NPC have mutations in the NPC1 gene, which encodes a protein that plays a central role in
modulating intracellular sorting of cholesterol and glycosphingolipids. Mutations may also be identified
in the NPC2 gene; see NPCMS/89015 Niemann-Pick Type C, Full Gene Analysis.
Useful For: Detection of a unique form of type C Niemann-Pick disease
Interpretation: Values expected in Niemann-Pick disease type C are