IllnessMorbus Niemann-Pick type C, differential diagnosis

NGS +

Niemann-Pick disease affects multiple body systems with a wide range of symptoms that vary in severity. It is divided into four main types: Type A and B (acid sphingomyelinase deficiency) as well as type C1 and C2. Types A and B are caused by mutations in the SMPD1 gene, which encodes acid sphingomyelinase in lysosomes. Over time, cell loss affects the function of tissues and organs such as the brain, lungs, spleen and liver. Mutations in the NPC1 or NPC2 gene cause Niemann-Pick disease type C and lead to lipid accumulation in cells, cell death and organ damage via transport deficiency. Infants with type A usually develop hepatosplenomegaly with failure to thrive by 3 months of age. At about 1 year of age, psychomotor regression, interstitial lung disease as well as the cherry red spot occur, and they do not survive early childhood. Niemann-Pick type B usually occurs in middle childhood. Symptoms are similar to those of type A but are less severe, and patients usually survive into adulthood. Types C1 and C2 usually present in childhood with ataxia, vertical supranuclear gaze palsy, dystonia, severe liver and interstitial lung disease. Patients with type C1 and C2 have problems with speech and swallowing that worsen over time. Affected individuals often experience progressive intellectual deterioration, about one-third have seizures. People with these types can survive into adulthood. All types are inherited in an autosomal recessive manner. The yield of DNA diagnostics depends largely on the preceding clinical characterization.

References: https://www.ncbi.nlm.nih.gov/books/NBK1370/

https://www.ncbi.nlm.nih.gov/books/NBK1296/

• Alias: Niemann-Pick disease, type A/B (SMPD1)
• Alias: Sphingomyelin lipidosis (SMPD1)
• Alias: Sphingomyelinase deficiency (SMPD1)
• Allelic: Hemorrhagic diathesis due to antithrombin Pittsburgh (SERPINA1)
• Allelic: Lewy body dementia, susceptibility to (GBA)
• Allelic: Macular dystrophy with central cone involvement (MFSD8)
• Allelic: Malignant hyperthermia susceptibility 5 (CACNA1S)
• Allelic: Parkinson disease, late-onset, susceptibility to (GBA)
• Allelic: Parkinson disease, susceptibility to (MAPT)
• Allelic: Thyrotoxic periodic paralysis, susceptibility to, 1 (CACNA1S)
• Aphasia, primary progressive (GRN)
• Ceroid lipofuscinosis, neuronal, 1 (PPT1)
• Ceroid lipofuscinosis, neuronal, 10 (CTSD)
• Ceroid lipofuscinosis, neuronal, 11 (GRN)
• Ceroid lipofuscinosis, neuronal, 13, Kufs type, AD (CTSF)
• Ceroid lipofuscinosis, neuronal, 2 (TPP1)
• Ceroid lipofuscinosis, neuronal, 3 (CLN3)
• Ceroid lipofuscinosis, neuronal, 4A, Kufs type, AR (CLN6)
• Ceroid lipofuscinosis, neuronal, 4B, Kufs type, AD (DNAJC5)
• Ceroid lipofuscinosis, neuronal, 5 (CLN5)
• Ceroid lipofuscinosis, neuronal, 6 (CLN6)
• Ceroid lipofuscinosis, neuronal, 7 (MFSD8)
• Ceroid lipofuscinosis, neuronal, 8 (CLN8)
• Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant (CLN8)
• Dementia, frontotemporal, with/-out parkinsonism (MAPT)
• Emphysema due to AAT deficiency (SERPINA1)
• Emphysema-cirrhosis, due to AAT deficiency (SERPINA1)
• Epilepsy, progressive myoclonic 3, with/-out intracellular inclusions (KCTD7)
• Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 (C9orf72)
• Frontotemporal dementia and/or amyotrophic lateral sclerosis 7 (CHMP2B)
• Frontotemporal lobar degeneration with ubiquitin-positive inclusions (GRN)
• GM2-gangliosidosis, several forms (HEXA)
• Gaucher disease, perinatal lethal (GBA)
• Gaucher disease, type I, II, III, IIIC (GBA)
• Glutaricaciduria, type I (GCDH)
• Hex A pseudodeficiency (HEXA)
• Hyperkalemic periodic paralysis, type 2 (SCN4A)
• Hypokalemic periodic paralysis, type 1 (CACNA1S)
• Hypokalemic periodic paralysis, type 2 (SCN4A)
• Maple syrup urine disease, type II (DBT)
• Maple syrup urine disease, type Ia (BCKDE1A)
• Maple syrup urine disease, type Ib (BCKDHB)
• Myasthenic syndrome, congenital, 16 (SCN4A)
• Myotonia congenita, atypical, acetazolamide-responsive (SCN4A)
• Neurovisceral storage disease with vertical supranuclear ophthalmoplegia (NPC1)
• Niemann-Pick disease without Sphingomyelinase deficiency (NPC1)
• Niemann-Pick disease, intermediate, protracted neurovisceral, type A (SMPD1)
• Niemann-Pick disease, intermediate, visceral involvement + rapid progression, type B/E/F (SMPD1)
• Niemann-Pick disease, type A (SMPD1)
• Niemann-Pick disease, type B (SMPD1)
• Niemann-Pick disease, type C1 (NPC1)
• Niemann-Pick disease, type C2 (NPC2)
• Niemann-Pick disease, type D (NPC1)
• Paramyotonia congenita (SCN4A)
• Pick disease (MAPT)
• Spinocerebellar ataxia, AR 7 (TPP1)
• Supranuclear palsy, progressive (MAPT)
• Supranuclear palsy, progressive atypical (MAPT)
• Tay-Sachs disease (HEXA)
• Tyrosinemia, type I (FAH)
• Wilson disease (ATP7B)