Niemann-Pick disease is a
heterogeneous group of autosomal recessive
lysosomal lipid storage disorders, characterized
by hepatosplenomegaly and sphingomyelin storage
in reticuloendothelial and parenchymal tissues,
with or without neurological involvement [1].
Case Report
We report a 9-month-old girl
born to a second degree consanguineously married
couple at term by normal delivery. She presented
with tremors of the tongue and tremors of right
upper and lower limbs of 35 days duration,
followed by shaking of head and trunk of 20 days
duration. Parents noticed paucity of movements
of right upper and lower limbs since the onset
of shaking. Child has also lost acquired
milestones. She used to sit with support,
transfer objects from one hand to other,
attained stranger anxiety, used to respond for
calling her name, and used to speak bisyllables.
After the onset of tremors child lost head
control, sitting, holding objects and social
smile. Child had exaggerated startle response.
On examination, child’s
weight, length and head circumference were
within normal limits. There was protrusion of
tongue, upward deviation of eyeballs and
rigidity with weakness of right upper and lower
limbs. Resting tremors of the tongue, right
upper and lower limbs were present. Head
titubation and truncal ataxia were noted. Cherry
red spot was not present. Liver was palpable 4
cm below the right costal margin and span of 8
cm with firm consistency. Spleen was palpable 4
cm below the costal margin and was firm in
consistency.
Investigations showed,
hemoglobin - 9.9 g/dL, total leucocyte count -
2400 cells/µL, platelets -2,43,000/µL. Liver
functions, renal functions, serum electrolytes
and lipid profile were normal. Ultrasonography
of abdomen shows moderately enlarged liver and
spleen with normal echo-texture, and multiple
mesenteric lymph nodes. Bone marrow aspiration
showed normocellular marrow, with storage cells
suggestive of Niemann-Pick disease. MRI of brain
was not done as bone marrow aspiration was
suggestive of Niemann-Pick cells. Acid
sphingo-myelinase activity in leucocytes showed
less than 10% of mean normal activity.
Discussion
Niemann-Pick disease type A
initially presents with non-neurological
manifestations. The first symptom is
hepatosplenomegaly, usually noted by the age of
three months; over time the liver and spleen
become massive [2]. Usually neurological
examination at the time of presentation can be
normal. Psychomotor development progresses no
further than 12-month level, after which
neurological deterioration is relentless. The
neurological findings can include cerebellar
signs, nystagmus, extra pyramidal involvement,
intellectual disability, and psychiatric
disorders [2]. A classic cherry-red spot, which
may not be present in the first few months, is
eventually present in all affected children.
Interstitial lung disease results in frequent
respiratory infections and often respiratory
failure can be present. Most children succumb
before the third year.
This child presented for the
first time with neurological features in the
form of tremors of one side of the body followed
by weakness of same side, with regression of
milestones. Neurologically, child had rigidity
of right side with tremors of tongue and right
half of the body with weakness. Initially we
suspected space occupying lesion in the brain,
as child had predominant unilateral signs.
Investigations shows decreased total counts with
mesenteric lymph nodes with hepato-splenomegaly
on ultrasonography of abdomen. CT scan of brain
was normal. Bone marrow examination shows
classic Niemann-Pick cells. Acid
sphingomyelinase assay confirms our diagnosis of
Niemann-Pick disease Type A. Prenatal diagnosis
can be made by assay of acid sphingomyelinase
activity in cultured chorionic villi or
amniocytes [3].
Unilateral involvement with
tremors in the initial stage, absence of cherry
red spot despite neurological involvement,
absence of lung involvement are unusual
presentations. There is no literature available
on this kind of unusual presentation.
Contributors: All authors
were involved in all aspects of manuscript
preparation.
Conflict of interest:
None.
References
1. Crocker AC, Farber S.
Niemann-Pick disease: a review of eighteen
patients. Medicine. 1958; 37:1-95.
2. Schuchman EH. The
pathogenesis and treatment of acid
sphingomyelinase-deficient Niemann-Pick disease.
J Inherit Metab Dis. 2007; 30:654-63.
3. McGovern MM, Aron A, Brodie
SE, Desnick RJ, Wasserstein MP. Natural history
of type A Niemann-Pick disease: possible
endpoints for therapeutic trials. Neurology.
2006;66:228-32.
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