What are the signs and symptoms of Niemann-Pick disease in a six-month-old?

1.

Elsevier ClinicalKey Clinical Overview

Diagnosis Sandhoff disease Rare hereditary disorder of lipid storage caused by deficiency in both β-hexosaminidase A and β-hexosaminidase B activities and characterized by progressive neurodegeneration; most commonly occurs in infants, with death by early childhood Clinical manifestations are similar to Tay-Sachs as most patients present in infancy with hyperacusis, neurologic regression, and cherry-red macula; rarely observed in Jewish patients Distinguish by the presence of organomegaly, skeletal abnormalities, and oligosacchariduria; hexosaminidase B activity is absent Niemann-Pick disease type A Hereditary metabolic disorder affecting young children with death by early childhood Some clinical manifestations are similar to Tay-Sachs as most patients present in infancy with failure to thrive, recurrent lung infections, cherry-red macula, psychomotor regression, and progressive loss of developmental milestones Distinguishing clinical feature of Niemann-Pick disease type A is prominent hepatosplenomegaly; hexosaminidase levels are within reference range Definitive testing by enzyme assays shows deficiency in acid sphingomyelinase activity Neuronal ceroid-lipofuscinosis (infantile, late infantile, and juvenile types) Group of progressive neurodegenerative disorders that affect infants and children with variable progression of disease; patients with early infantile form do not live past childhood, those with late infantile form do not live past teenage years, and those with juvenile form do not live past third decade of life Clinical manifestations are similar to Tay-Sachs as patients present with psychomotor retardation, seizures, ataxia, hypotonia, visual impairment, spasticity, and neurologic impairment Distinguish from Tay-Sachs by hexosaminidase levels within the reference range

2.

National Library of Medicine (MedlinePlus)

Publish date: January 4, 2015.

Description Niemann-Pick disease is a condition that affects many body systems. It has a wide range of symptoms that vary in severity. Niemann-Pick disease is divided into four main types: type A, type B, type C1, and type C2. These types are classified on the basis of genetic cause and the signs and symptoms of the condition. Infants with Niemann-Pick disease type A usually develop an enlarged liver and spleen (hepatosplenomegaly) by age 3 months and fail to gain weight and grow at the expected rate (failure to thrive). The affected children develop normally until around age 1 year when they experience a progressive loss of mental abilities and movement (psychomotor regression). Children with Niemann-Pick disease type A also develop widespread lung damage (interstitial lung disease) that can cause recurrent lung infections and eventually lead to respiratory failure. All affected children have an eye abnormality called a cherry-red spot, which can be identified with an eye examination. Children with Niemann-Pick disease type A generally do not survive past early childhood. Niemann-Pick disease type B usually presents in mid-childhood. The signs and symptoms of this type are similar to type A, but not as severe. People with Niemann-Pick disease type B often have hepatosplenomegaly, recurrent lung infections, and a low number of platelets in the blood (thrombocytopenia). They also have short stature and slowed mineralization of bone (delayed bone age). About one-third of affected individuals have the cherry-red spot eye abnormality or neurological impairment. People with Niemann-Pick disease type B usually survive into adulthood. The signs and symptoms of Niemann-Pick disease types C1 and C2 are very similar; these types differ only in their genetic cause. Niemann-Pick disease types C1 and C2 usually become apparent in childhood, although signs and symptoms can develop at any time.

3.

Geberhiwot T, Wasserstein M, Wanninayake S, et al. Consensus Clinical Management Guidelines for Acid Sphingomyelinase Deficiency (Niemann-Pick Disease Types A, B and a/B). Orphanet Journal of Rare Diseases. 2023;18(1):85. doi:10.1186/s13023-023-02686-6. Copyright License: CC BY

Publish date: April 1, 2023.

Most infants present with hepatosplenomegaly at 2–4 months of age [29] followed by onset of neurologic symptoms at a median age of 7 months, developmental arrest by 10 months of age and then rapidly progressing neurodegeneration with deterioration of behavioral, language and gross and fine motor skills. Patients show progressive hypotonia with loss of deep tendon reflexes, whereas cranial nerve function remains largely intact. Macular cherry-red spots are detectable in most infants by 12 months. These infants suffer from failure to thrive due to insufficient intake of calories resulting from worsening hypotonia, weakened suck and gastrointestinal symptoms. All infants develop progressive restrictive pattern of respiratory symptoms due to the accumulation of Niemann–Pick cells in the alveolar septa, bronchial walls, and pleura with frequent respiratory infections secondary to aspiration, and most die of respiratory failure. Massive hepatosplenomegaly is typically present, and most infants have significant hepatic dysfunction or liver failure. Abnormal laboratory values include elevated liver enzymes, low HDL cholesterol and progressive decreases in hemoglobin values and platelet counts. (Table 3). What is the clinical presentation in Chronic Visceral ASMD type B? Statement 4: The onset of ASMD type B is variable, from childhood to adulthood. Patients with ASMD type B have extensive phenotypic heterogeneity in disease manifestations, from asymptomatic to polysymptomatic. Progression of disease can vary considerably and stability can also be seen in attenuated older patients. The most common symptoms at initial presentation are splenomegaly and hepatomegaly. Common historical symptoms and complaints may include bleeding, shortness of breath, pulmonary involvement, joint and/or limb pain, bruising, headaches, diarrhea and bone fractures. Interstitial lung disease, abnormal blood counts and/or atherogenic lipid profile can be seen. Being a rare disease and having variable phenotypic manifestations lead to misdiagnosis of ASMD, especially in the later onset group (type B). The systemic involvement in later onset ASMD (types A/B and B) can present anytime from early childhood to adulthood and sometimes requires a high index of suspicion to make a diagnosis.