Niemann-Pick Type A: Causes, Symptoms, Diagnosis, and Treatment

This essay discusses Niemann-Pick Type A, a rare genetic disorder characterized by the accumulation of lipids in the liver, spleen, and brain cells. It explores the causes, symptoms, diagnosis, and treatment options for this condition. The essay also highlights the importance of research and support groups in improving the lives of patients.

Running head: NIEMANN-PICK TYPE A 1
Niemann-Pick Type A
Students Name
Institution Affiliation

NIEMANN-PICK TYPE A 2
Introduction
Niemann-pick disorder is a group of genetic lysosomal disorders that are inherited
whereby fatty substances, namely lipids, accumulate in the liver, spleen, and brain cells. There
are three common forms of the Niemann-pick disorder namely type A, B, and C. Each type of
the disorder involves different organs and cause diversified symptoms and maybe witnessed at
different times in an individual’s life (1,2). The disease emanates from deficient functions of
Sphingomyelin phosphodiesterase (Enzyme Commission number: 3.1.4.12) (3). This essay aims
at discussing Niemann-pick disease type A disorder and current research present relevant to the
condition. The report will have four sections, namely, research, diagnosis, treatment, and policy.
Research
Niemann-pick type A is approximated to affect at least 1: 250,000 individuals. The
conditions occur more commonly Ashkenazi Jewish descent of Central and Eastern European
compared to the rest of the population. The prevalence within this population is approximated to
be 1 in 40,000 people. Mutations in the SMPD1 gene cause Niemann-pick type A disease. The
gene has an autosomal inheritance pattern. When a mutation occurs in one of the lysosomal
enzymes, there is an abnormal accumulation of the product which consequently is not
transformed by the Sphingomyelin phosphodiesterase enzyme (3). This, therefore, means the
cells cannot eliminate the accumulated substrates leading in cell damage and failure of the organ
where the accumulation is taking place (4). The SMPD1 gene is responsible for the provision of
instruction for the production of enzyme sphingomyelinase.
Niemann-pick type A disorder occurs in infancy by the age of three months and is
evidenced by an enlarged spleen and liver (hepatosplenomegaly) the failure of gaining weight

NIEMANN-PICK TYPE A 3
and grow at the anticipated rate (failure to thrive), and progressive decline of the nervous system
(4). Children with the disorder usually develop until they are one year of age when they start to
experience a gradual loss in their mental ability and psychomotor regression. The infants with
the disorder also experience an extensive lung malfunction (interstitial lung condition) that lead
to repeated lung contamination and consequently leading to lung failure (3). Due to the nervous
system involvement, the disorder is also identified among the neurological group of diseases. All
affected infants have eye anomaly termed as a cherry-red spot, which is identifiable thorough
eyes examination. The children with the disorder do not survive past early childhood.
Diagnosis
Individuals with this disorder experience some features including an engorged spleen and
liver, failure to thrive, frequent lung infections, neurological complications, developmental
delays, increased risk of abnormal blood clots, seizures, and muscle tone (5,6). Due to the rarity
of the condition, making a diagnosis of the genetic disease is often challenging. The diagnosis of
the disorder is based on medical history, physical exam, symptom, and laboratory test results.
The diagnosis of the condition begins through a physical exam, which is important in the
determination of the early warning signs, for instance, enlarged spleen, or liver. The condition
can be defined by (biopsy) using blood or a skin sample to determine how much
sphingomyelinase is found in the blood to confirm the analysis. Other diagnosis techniques
include Magnetic resonance imaging (MRI) of the bran to show damage of brain cells. An MRI
at the early stages may be identified as normal since symptoms occur before the loss of the cells
of the brain. Genetic examination of a blood sample can be used to identify the abnormal genes
attributed to the conditions (3,6). The DNA examinations can indicate the carriers of the disorder
if the mutations are defined in the first individual in a family. Eye examination of the suspected

NIEMANN-PICK TYPE A 4
patient can show the signs that are an indication of the disorder, for instance, eye movement
problems.
Treatment
Niemann-pick type A disorder is autosomal recessive hence, the parents are identified as
the carriers of the genes leading to the condition (7). Each of the parents has a copy of the gene;
however, they do not exhibit any signs themselves. With both parents being carriers, there is a
25 % possibility that their offspring will have the disorder, and there is a 50% chance their
children will be a carrier of the abnormal genes (3). Carrier detection testing is only probable if
the genetic abnormality is found.
Presently no treatment has been approved or identified as useful for the treatment of type
A disorder; however, supportive care is crucial in dealing with the disease. Children often die
from infection and progressive neurological loss. However, scientists continue to study probable
treatments of the condition, including gene therapy and enzyme replacement (4). There are
however, recommendations to prolong life through the management by consumption of low
cholesterol diets and medications (8). There is, however, no research to show whether these
methods can stop the disorder from getting worse or alter how cells break down cholesterol (10).
Drugs are available to relieve and control some of the disorder’s symptoms, for instance, seizures
and loss of muscle tones.
Policy
Research is being carried out to define the cure or prevention mode of the condition.
Advocacy and supports group are highly recommended for parents with children having the
disorder (8). The groups are essential in the connection of families and patients and can provide

NIEMANN-PICK TYPE A 5
valuable services attributed to the condition (11). Patient-centred data is developed in the groups,
which are essential in driving research and better treatments and cures. Many groups have
experts or at least have individuals with knowledge who can help in advising or offering
important information related to the condition. A DNA test to determine compatibility is also
highly recommended for people who come from families with a history of the disorder (2, 12). A
team of medical practitioners and researchers identified as lysosomal disease network are
working towards the identification of better ways of improving the lives of the patients as they
try to look for a cure.
Conclusion
Niemann-pick type A disorder is rare; however, it is identified to be a significant cause of
death to underage children. The disease has no cure however the condition can be prevented by a
proper screening of individuals who are in the same bloodline with persons who have been
diagnosed with the conditions or carry the abnormal genes leading to the disease. A DNA test to
determine the disease is available.

NIEMANN-PICK TYPE A 6
Reference list
1. Irun P, Mallén M, Dominguez C, Rodriguez‐Sureda V, Alvarez‐Sala LA, Arslan N,
Bermejo N, Guerrero C, Perez de Soto I, Villalón L, Giraldo P. Identification of seven
novel SMPD1 mutations causing Niemann–Pick disease types A and B. Clinical genetics.
2013 Oct;84(4): p.356-360. Available from
https://onlinelibrary.wiley.com/doi/abs/10.1111/cge.12076
2. Patterson MC, Nordli DR, Dashe JF. Overview of Niemann-Pick Disease. Literature
Review Current Through: June 2017. 2017.p.2-27 Available from
https://www.uptodate.com/contents/overview-of-niemann-pick-disease
3. Rappaport J, Manthe RL, Solomon M, Garnacho C, Muro S. A comparative study on the
alterations of endocytic pathways in multiple lysosomal storage disorders. Molecular
pharmaceutics. 2016 Jan 11;13(2): p.357-367. Available from
https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.5b00542
4. Rodriguez-Muela N, Hernandez-Pinto AM, Serrano-Puebla A, Garcia-Ledo L, Latorre
SH, De La Rosa EJ, Boya P. Lysosomal membrane permeabilization and autophagy
blockade contribute to photoreceptor cell death in a mouse model of retinitis pigmentosa.
Cell death and differentiation. 2015 Mar;22(3):p.476-483. Available from
https://www.nature.com/articles/cdd2014203
5. Schuchman EH, Wasserstein MP. Types A, and B Niemann-Pick disease. Best practice &
research Clinical endocrinology & metabolism. 2015 Mar 1;29(2): p.237-246. Available
from https://www.sciencedirect.com/science/article/abs/pii/S1521690X14001249
6. Santos-Lozano A, García DV, Sanchis-Gomar F, Fiuza-Luces C, Pareja-Galeano H,
Garatachea N, Gadea GN, Lucia A. Niemann-Pick disease treatment: a systematic review

NIEMANN-PICK TYPE A 7
of clinical trials. Annals of translational medicine. 2015 Dec;3(22). p.5-9. Available from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701532/
7. Vanier MT. Niemann–pick diseases. InHandbook of clinical neurology. Elsevier; 2013
Jan 1 (Vol. 113) p.1717-1721. Available from
https://www.sciencedirect.com/science/article/pii/B9780444595652000411
8. Schuchman EH, Desnick RJ. Types a and B Niemann-pick disease. Molecular genetics
and metabolism. 2017 Jan 1;120(1-2):p.27-32. Available from
https://www.sciencedirect.com/science/article/abs/pii/S1096719216303171
9. KEGG:Kyoto Encyclopedia of Genes and Genomes. Retrieved from
https://www.genome.jp/kegg/ Accessed on (2019, September 8).
10. Gabande-Rodriguez, E., Boya, P., Labrador, V., Dotti, C. G., & Ledesma, M. D. (2014).
High sphingomyelin levels induce lysosomal damage and autophagy dysfunction in
Niemann Pick disease type A. Cell death and differentiation, 21(6), 864. Available from
https://www.nature.com/articles/cdd20144
11. Ledesma, M. D., Prinetti, A., Sonnino, S., & Schuchman, E. H. (2011). Brain pathology
in Niemann Pick disease type A: insights from the acid sphingomyelinase knockout
mice. Journal of neurochemistry, 116(5), 779-788. Available from
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1471-4159.2010.07034.x
12. Gülhan, B., Özçelik, U., Gürakan, F., Güçer, Ş., Orhan, D., Cinel, G., ... & Kale, G.
(2012). Different features of lung involvement in Niemann-Pick disease and Gaucher
disease. Respiratory medicine, 106(9), 1278-1285.