Byline: Shruti. Mishra, Kishalaya. Karan, Dipanwita. Nag, Prosenjit. Sengupta
Niemann–Pick disease Type C (NPC) is a rare lysosomal storage disorder of autosomal recessive inheritance. It is characterized by neuro-visceral manifestations. The main defects occur due to accumulation of unesterified cholesterol and glycolipids within the lysosomal system.[sup], The pattern in which the lipids accumulate within the tissues is different in the brain and in non-neural organs. Two genes are found to be affected. The most common are mutations in the NPC 1 gene (18q11), seen in 95% of patients. This gene encodes a large membrane glycoprotein which localizes in late lysosomes. The rest have mutations in the NPC2 gene (14q24.3), which encodes a high-affinity cholesterol binding a small soluble lysosomal protein.[sup],
The NPC1 and NPC2 genes have a nonredundant functional cooperativity. The two proteins either function in tandem or in sequence. Their main function appears to be related to postlysosomal transport of cholesterol, glycolipids, and other molecules. However, their precise functions, mechanisms and interactions remain unclear with an elusive primary substrate.[sup],, Currently, NPC is biochemically diagnosed by demonstrating impaired low-density lipoprotein (LDL)-cholesterol trafficking in cultured fibroblasts of patients. Filipin stain is used on these cultured fibroblasts to visualize the accumulated free cholesterol and also to study the LDL-induced cholesterol ester formation.[sup]
The epidemiology of this disease in India is not known as yet. This is a rare disease and the adult form of this disease is rarer still. However, the disease may be underdiagnosed due to its highly heterogeneous presentation. The presentations of these cases are varied and there are no fixed criteria for the diagnosis of this disease. We attempt to critically analyze both our patient's symptomatology and investigational findings which may help in establishing a better diagnosis of this entity in the future.
The first patient, a forty-year-old male patient, a product of nonconsanguineous marriage, residing at a remote village of West Bengal, cultivator by profession, presented with several neurological signs and symptoms. All his troubles began 11/2 years back when he experienced progressive anosmia. This was followed by the onset of slurring of speech, difficulty in deglutition to both liquid and solid food material, and occasional abnormal posturing of the distal part of upper limbs 1/2 year later. He also developed a tendency to fall while walking, 6 months later. All these events were insidious in onset and slowly progressive in nature.
There was no history of unconsciousness, seizures, headache, or memory impairment. The patient had no complaints regarding either limb weakness, subjective sensory impairment or cranial nerve involvement. The bowel and bladder functions were normal and there was neither associated weight loss nor fever. The patient was nonhypertensive and nondiabetic.
His general examination was normal. Neurological examination revealed a dysarthric speech, with imprecise consonants. The spine and cranium were normal and there were no signs of meningeal irritation. Upon conducting a cranial nerve examination, it was found that bilateral olfactory nerves were affected leading to diminished olfaction. Another finding was the presence of vertical gaze palsy...