The National Niemann–Pick C1 disease database: Report of clinical features and health problems

Abstract

Niemann-Pick type C1 (NPC1) disease is an autosomal recessive disorder characterized clinically by neonatal jaundice, hepatosplenomegaly, vertical gaze palsy, ataxia, dystonia, and progressive neurodegeneration. The present study provides basic clinical and health information from the National Niemann-Pick C1 disease database that was obtained using a clinical questionnaire of 83 questions mailed to families affected by NPC1 disease living in the United States. The study was conducted over a 1-year period, during which time parents/caregivers and physicians completed the clinical questionnaire. Sixty-four percent (87/136) of the questionnaires were returned, with 53% and 47% representing male and female NPC1 patients, respectively. The average age of diagnosis for NPC1 disease was 10.4 years, with one-half of patients being diagnosed before the age of 6.9 years. The average age of death for NPC1 disease was 16.2 years, with one-half of patients dying before the age of 12.5 years. A common clinical symptom reported at birth was neonatal jaundice (52%), followed by enlargement of the spleen (36%) and liver (31%); ascites (19%) and neonatal hypotonia (6%) were much less frequent. With respect to developmental difficulties, the most common findings included clumsiness (87%), learning difficulties (87%), ataxia (83%), dysphagia (80%), and vertical gaze palsy (81%). Together, these findings confirm and extend previous reports investigating the clinical features associated with NPC1 disease.

Differential Association of Niemann-Pick C1 Gene Polymorphisms with Maternal Prepregnancy Overweight and Gestational Diabetes

“…Subsequent studies performed to determine the transferability of NPC1 obesity risk alleles have also discovered alleles associated with decreased fasting insulin levels and increased risk for type 2 diabetes independent of body weight in other populations [10][11][12] . These findings were noteworthy since NPC1 mutations were originally known to be responsible for a rare and fatal autosomal-recessive lipid-storage disorder called NPC1 disease [13,14] . With respect to this disease, the NPC1 derived and minor allele for 3182T>C encoding the Ile1061Thr residue predisposes to most diagnosed cases of NPC1 disease in the United States, particularly among Hispanic patients living in the Northern Rio Grande Valley region of New Mexico and Colorado [14] .…”

Antisense Mediated Splicing Modulation For Inherited Metabolic Diseases: Challenges for Delivery

“…It is characterized by the accumulation of cholesterol and glycosphingolipids that leads to hepatic disease and progressive neurological impairment. The majority of NPC patients die in their teen years due to the progressive neurodegenerative process; however, their liver disease is also significant (Garver et al, 2007).…”

Impact of selected inborn errors of metabolism on prenatal and neonatal development

“…Intrauterine growth retardation, oligohydramnion, congenital thrombocytopenia, and anemia were present as well. As congenital hepatosplenomegaly is well documented after birth in term Morbus Niemann-Pick type C infants, Morbus Niemann-Pick type C should be considered in the differential diagnosis of in utero splenomegaly with or without hepatomegaly, and unexplained fetal ascites (38,39,41,42). Neurodegeneration usually sets in later during puberty or young adulthood.…”