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# Niemann–Pick disease

In Niemann–Pick disease lipids build up in the liver, spleen, lungs and, in some forms, the brain.

Updated 2026-11-01

## Structures involved

Tap one to see what it is and open it in 3D.

- [Spleen](https://durgical.com/en/anatomy/spleen/)
- [Liver](https://durgical.com/en/anatomy/liver/)
- [Right lower lobe](https://durgical.com/en/anatomy/inferior-lobe-of-right-lung/)
- [Left lower lobe](https://durgical.com/en/anatomy/inferior-lobe-of-left-lung/)
- [Macula](https://durgical.com/en/anatomy/macula/)

## In biochemistry

- [Sphingolipids and sphingolipidoses](https://durgical.com/en/biochemistry/topics/sphingolipids-and-sphingolipidoses/)
- [Lysosomal storage diseases](https://durgical.com/en/biochemistry/topics/lysosomal-storage-diseases/)
- [Ceramide](https://durgical.com/en/biochemistry/molecules/ceramide/)
- [Sphingomyelin](https://durgical.com/en/biochemistry/molecules/sphingomyelin/)
- [Acid sphingomyelinase](https://durgical.com/en/biochemistry/enzymes/acid-sphingomyelinase/)

## Why it happens

- [Intracellular accumulations: cholesterol, proteins, hyaline, glycogen](https://durgical.com/en/general-pathology/intracellular-accumulations-cholesterol-proteins-hyaline-glycogen/)
- [How a single gene causes disease: enzymes, receptors and structural proteins](https://durgical.com/en/general-pathology/how-a-single-gene-causes-disease-enzymes-receptors-and-structural-proteins/)

## What it is

A group of autosomal recessive lysosomal diseases: types A and B from acid sphingomyelinase deficiency (SMPD1 gene), and type C from a defect of cholesterol transport (NPC1 or NPC2 genes).

## Who gets it

Types A and B affect about 1 in 250,000 people; type A is more common in Ashkenazi Jews. Types C1 and C2 together affect about 1 in 150,000, and C1 accounts for 95% of them.

## Causes

- Types A and B: biallelic SMPD1 variants
- Type C: biallelic variants of NPC1 (most) or NPC2

## Risk factors

- Carrier parents
- Ashkenazi Jewish ancestry (type A)

## Pathophysiology

In types A and B, without acid sphingomyelinase, sphingomyelin builds up in macrophages of liver, spleen, lung and bone marrow (foam cells) and, in type A, also in neurons, with a cherry-red spot. In type C the enzyme is normal, but cholesterol from engulfed lipoproteins cannot leave the lysosome; free cholesterol and glycolipids accumulate, mostly in brain and liver.

## Classification

- Type A (infantile neurovisceral): hepatosplenomegaly and regression from the first months
- Type B (chronic visceral): hepatosplenomegaly, lung disease and dyslipidaemia, with little or no neurological disease
- Type C: prolonged neonatal jaundice or splenomegaly, then ataxia, vertical gaze palsy, cataplexy and dementia

## Symptoms and signs

- Large [abdomen](https://durgical.com/en/anatomy/region/abdomen/) from hepatosplenomegaly
- Poor weight gain and feeding difficulty in infants
- Loss of skills and stiffness (type A)
- Cough and breathlessness from interstitial lung disease (type B)
- Clumsy walking, falls and trouble looking up or down (type C)
- Sudden loss of muscle tone when laughing (cataplexy, type C)

## Red flags

- Infant with hepatosplenomegaly and developmental regression
- Prolonged neonatal cholestatic jaundice with splenomegaly
- Child or young adult with ataxia, vertical gaze palsy and cognitive decline

## Diagnosis

**Clinical**
Hepatosplenomegaly with or without neurological disease; look for a cherry-red spot (type A) and vertical supranuclear gaze palsy (type C).

**Tests**
Low acid sphingomyelinase activity in leukocytes or dried blood spots (A and B); plasma biomarkers (lyso-sphingomyelin, oxysterols); SMPD1, NPC1 and NPC2 testing; lipid profile with low HDL; marrow may show foamy or sea-blue histiocytes.

**Imaging**
Abdominal ultrasound or MRI for [liver](https://durgical.com/en/anatomy/liver/) and [spleen](https://durgical.com/en/anatomy/spleen/) size; [chest](https://durgical.com/en/anatomy/region/chest/) CT with an interstitial pattern; brain MRI in type C.

## Treatment

**Medical**
Enzyme replacement with recombinant acid sphingomyelinase for the non-neurological features of acid sphingomyelinase deficiency (types A/B).

**Medical**
In type C, miglustat may slow neurological decline; cataplexy and seizures are treated.

**Follow-up**
Follow-up of lung function, liver, lipids and growth.

**Rehabilitation**
Physiotherapy, speech and swallowing therapy in the neurological forms.

## Complications

- Respiratory failure from interstitial lung disease
- Cirrhosis and portal hypertension
- Bleeding from hypersplenism
- Aspiration pneumonia in the neurological forms

## Prognosis

Type A is usually fatal before age 3. In type B many patients reach adulthood. Type C varies with the age at which neurological symptoms begin.

## Test yourself

Think of the answer, then tap the question to see it.

## Which enzyme is missing in Niemann–Pick types A and B?

Acid sphingomyelinase (SMPD1 gene); sphingomyelin accumulates.

## What fails in Niemann–Pick type C?

Cholesterol export from the lysosome (NPC1 or NPC2 proteins); sphingomyelinase is normal.

## Which eye finding do Niemann–Pick A and Tay–Sachs share, and what tells them apart?

Both have a cherry-red spot; Niemann–Pick A also has hepatosplenomegaly.

## Which neurological sign is typical of type C?

Vertical supranuclear gaze palsy, often with ataxia and cataplexy.

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## Related conditions

- [Gaucher disease](https://durgical.com/en/conditions/gaucher-disease/)
- [Tay–Sachs disease](https://durgical.com/en/conditions/tay-sachs-disease/)
- [Interstitial lung disease](https://durgical.com/en/conditions/interstitial-lung-disease/)
- [Cirrhosis](https://durgical.com/en/conditions/cirrhosis/)
- [Portal hypertension](https://durgical.com/en/conditions/portal-hypertension/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Niemann-Pick disease: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/niemann-pick-disease/) (MedlinePlus, US National Library of Medicine, 2026); [SMPD1 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/smpd1/) (MedlinePlus, US National Library of Medicine, 2026); [NPC1 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/npc1/) (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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Source: https://durgical.com/en/conditions/niemann-pick-disease/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/niemann-pick-disease/