Niemann-Pick disease (NPD) is an autosomal recessive disorder, observed most frequently in Ashkenazi Jews, where there is a deficiency of the lysosomal enzyme sphingomyelinase, leading to accumulation of sphingomyelin in cells of the monocyte-macrophage system and reticular endothelial cells.
Patients with type A NPD appear normal at birth but start to display signs, such as hepatosplenomegaly, in early infancy. In type A NPD less than 5% or sphingomyelinase activity is observed and along with hepatosplenomegaly, patients display a failure to thrive, feeding problems, interstitial lung disease resulting in recurrent respiratory tract infections, motor and intellectual developmental delays followed by regression, irritability, cherry-red macula, pancytopenia, progressive neurodegeneration and eventually death by age two or three. Progressive hepatosplenomegaly is usually apparent by three months and mild hypotonia may appear by 6 months leading to loss of tone and deep tendon reflexes (previously achieved milestones may be lost). Psychomotor skills of type A patients do not progress beyond the 12 month level (eg. sit with assistance). The final stage of type A NPD is characterized by spasticity and rigidity. Although uncommon, some patients present unilateral tremors and ipsilateral hemiparesis .
Patients with type B NPD have 5-10% of normal sphingomyelinase activity and display more variable severity of symptoms, clinical findings and age of onset than type A. Hepatosplenomegaly is a hallmark of both types of NPD and lymphadenopathy may occur in patients with type B. Patients with type B NPD have minimal neurologic involvement but pancytopenia is common. Pulmonary involvement may be observed in type B NPD patients which is detected on chest radiographs as diffuse reticular or finely nodular infiltration. Severe pulmonary complications may arise in patients with type B NPD due to progressive pulmonary infiltrates. It is common for type B NPD patients to survive into adulthood and often it is hard to distinguish these patients from patients with Gaucher disease type 1. Growth retardation may be observed in patients with moderate-to-severe type B NPD  .
Mildly affected patients may have minimal disease manifestations and hepatosplenomegaly may not be detected until adulthood.
NPD may be suspected due to familial history along with identification of hepatosplenomegaly upon physical examination. Diagnosis may be confirmed pre or postnatal, using a sphingomyelinase assay on amniocentesis or chorionic villus sampling and white blood cells (WBCs), respectively. The hallmark of NPD is characteristic lipid-laden foam cell on bone marrow examination, although, genetic tests are needed for definitive diagnosis . Along with hepatosplenomegaly patients often display pancytopenia (secondary to splenomegaly), elevated transaminase, total cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels. Patients with type B NPD commonly have reduced high-density lipoprotein (HDL-C) fraction and these patients often display hypertriglyceridemia. Pulmonary reticulonodular patterns of infiltration and calcified nodules may be observed in chest radiographs of NPD patients with or without pulmonary symptoms. Patients often display decreased oxygen diffusion, restrictive lung disease and exercise intolerance. A lag in bone age of up to two and a half years may be observed in NPD type B patients. Myocardial dysfunction and valvular heart disease can be diagnosed with an echocardiogram (ECHO), which are especially prevalent in NPD patients with underlying coronary artery disease .
Clinical laboratories are equipped to identify the four most common SMPD1 mutations responsible for NPD. Three common mutations have been identified in type A NPD patients (L302P, R495L and fsP330) and one common allele in type B (deltaR608). Another less common mutation, Gln294Lys, is associated with a milder form of type B NPD. Patients with the Gly294Lys mutation may not show decreased sphingomyelinase function in tests where the artificial substrate is used . Mutation analysis is available for rare or specific gene mutations which can provide useful information for genotype-phenotype correlations and prenatal diagnosis for family members.
No specific treatments are available for patients with type A NPD and current treatment modalities focused on symptom management. Novel therapies, such as bone marrow, stem cell transplants and enzymatic replacement, are currently being tested as a treatment option for patients with NPD  . Liver and amniotic cell transplantation have been attempted in infants with type A NPD with minimal success.
Adults with type B NPD that have elevated cholesterol should receive treatments to lower cholesterol levels to normal range. If statins are used, liver function should be monitored. Patients with type B NPD that experience acute bleeding secondary to an overactive spleen and thrombocytopenia may require blood transfusions. Affected individuals with pulmonary disorders, including interstitial lung disease, may be administered oxygen or bronchopulmonary lavage (although this has mixed results). Bone marrow transplants have shown some success in treating type B NPD patients by reducing hepatosplenomegaly, increasing peripheral blood counts and decreasing lung infiltration, however, this is not recommended for patients with neurological symptoms.
Type A NPD is extremely serious and is characterized by failure to thrive, hepatoslenomegaly, interstitial lung disease, cherry-red macula, progressive neurodegeneration and eventually death by age three. Children with type A NPD appear normal at birth. Severity of symptoms, clinical findings and age of onset for patients with Type B NPD are typically more variable than type A and symptoms are often milder, including neurological signs which may be absent .
Patients are usually diagnosed during early childhood or infancy when physicians notice hepatoslenomegaly upon physical examination. Patients with type A NPD exhibit neurodegeneration beginning at three months of age and death by three years of age. Patients with type B NPD often survive into adulthood  .
NPD is a sphingolipidosis characterized by a deficiency in sphingomyelinase caused by an autosomal recessive gene. Sphingomyelinase deficiency leads to lysosomal accumulation of sphingomyelin. The sphingomyelinase gene is located on chromosome 11 (11p15.1 to p15.4). The primary cell types affected by this disease are cells in the monocyte-macrophage system along with reticuloendothelial cells.
Type A NPD is extremely serious and is characterized by failure to thrive, hepatoslenomegaly, interstitial lung disease, cherry-red macula, progressive neurodegeneration and eventually death by age three. Type B NPD is regarded as a milder form of the disease, without neurological signs, that has a later-onset, however, there is much overlap between type A and B. A number of mutations have been identified to cause NPD, including deletions and substitutions.
NPD is an autosomal recessive disorder that affects more commonly Ashkenazi Jews, people of Turkish decent and individuals who reside in the Maghreb region of North Africa and Saudi Arabia, however, it does occur rarely in all races and geographical locations   . Males and females are affected equally by both types of NPD. The onset and severity of type A and type B NPD vary from early onset and death by age three to later onset and survival into adulthood, respectively.
NPD is caused by an autosomal recessive mutation of the Sphingomyelin Phosphodiesterase 1 (SMPD1) gene located on chromosome 11 (11p15.1-p15.4) that results in sphingomyelinase deficiency  . Genomic studies have revealed that three mutations (L302P, 1bp del fsP330, R496L) are responsible for 90% of type A NPD cases and the deltaR608 mutation is most commonly found in type B NPD. Patients with NPD demonstrate less than 10% of sphingomyelinase activity compared to unaffected individuals. Sphingomyelinase deficiency leads to the accumulation of sphingomyelin in cells of the monocyte-macrophage system as well as reticuloendothelial cells. Systemic manifestations are observed in both type A and type B, including progressive lung disease, hepatosplenomegaly, short stature, and pancytopenia, whereas, neurodegenerative signs are primarily observed in patients with type A .
Dietary supplements are often needed for pediatric patients with type B NPD who experience early satiety due to hepatosplenomegaly. High calorie supplements may be beneficial. Patients with splenomegaly have increased risk of splenic rupture, therefore, contact sports should be avoided. If trauma occurs in NPD patients with hyperslenism, immediate medical care should be administered to address risk of splenic rupture and intracranial bleeding.
Type A and B Niemann-Pick disease (NPD) result from an autosomal recessive gene that causes a deficiency in the enzyme sphingomyelinase which leads to a sphingolipidosis associated with the accumulation of sphingomyelin. Type A NPD is a fatal disorder in young children characterized by failure to thrive, hepatosplenomegaly and progressive neurodegeneration resulting in death by age three. There is much overlap between type A and B NPD, however, type B is generally less severe. Type C NPD is an unrelated disorder associated with abnormal cholesterol storage. The occurrence of NPD is 1 in 248,000 .
Niemann-Pick disease (NPD) is a genetic disorder associated with a deficiency of the enzyme, sphingomyelinase, which results in the accumulation of sphingomyelin or cholesterol in tissues. There are different forms of NPD, based on the level of sphingomyelinase deficiency, with the most severe form (type A) found to occur most commonly in Jewish patients and the milder form (type B) occurring in any ethnic group (although rarely). Patients with type A NPD experience severe growth complications and neurologic problems starting in infancy and typically don’t survive past age three. Usually, patients with type B NPD survive into adulthood and do not experience neurologic symptoms. Patients with type B NPD may develop fatty growths and areas of dark pigmentation on the skin, enlarged liver, spleen and lymph nodes and in some cases possess intellectual disabilities.
Some tests can be performed, including amniocentesis and chorionic villus sampling, to diagnose certain forms of NPD in a developing fetus. Diagnosis can be achieved after birth through analysis of tissue samples, including liver and blood, and genetic tests. There is no cure for NPD and in severe cases children die early from central nervous system dysfunction or infection. New therapies are being developed that are showing promise in preclinical studies but none have been approved for treatment of NPD.