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Neurofibromatosis – 1 in 3500 have it, associated with low vitamin D

NF is similar to Multiple Sclerosis:

  1. Both have brain lesions
  2. Both are treated by Vitamin D
    See NF - Vitamin D Clinical Trial listed below - results due ~2021
  3. Both are treated by UVB
  4. Both have more problems if poor Vitamin D Receptor
  5. Both have similar cormorbidities (autism, ADHD, etc)

Note: Multiple Sclerosis rate is 3X that of NF about 1 in 1,000

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Overview NF

Neurofibromatosis has a 50 percent chance of developing in a child who has one parent with the mutated gene.
Type NF1 neurofibromatosis affects one in 3,000-4,000 people in the U.S.
50 percent of NF1 cases are inherited, the other half occur spontaneously
There are no known ethnic groups in which NF1 does not occur or is unusually common

Vitamin D lower in children with NF – perhaps because indoors

Pediatric 25-hydroxyvitamin D concentrations in neurofibromatosis type 1.
J Pediatr Endocrinol Metab. 2011;24(3-4):169-74.
Stevenson DA1, Viskochil DH, Carey JC, Sheng X, Murray M, Moyer-Mileur L, Shelton J, Roberts WL, Bunker AM, Hanson H, Bauer S, D'Astous JL.
1Department of Pediatrics, University of Utah, Salt Lake City, UT 84132, USA. david.stevenson at hsc.utah.edu

Low 25-hydroxyvitamin D (25OHD) concentrations have been associated with tumors and osteopenia or fractures in adults with neurofibromatosis type 1 (NF1). We report 25OHD concentrations in 109 children with NF1 and 218 controls matched for age, sex, geographic location, and time of year.

Children with NF1 were recruited (n=109; 2-17 years), and clinical data and dual-energy X-ray absorptiometry measurements were obtained. 25OHD concentrations were measured in subjects and controls.

More NF1 individuals (50%) were in the 25OHD insufficient or deficient range (<30 ng/mL) (1 ng/mL = 2.496 nmol/L) compared to controls (36%) (p = 0.0129). 25OHD concentrations were higher in individuals with neurofibromas after controlling for age (p = 0.0393), and were negatively associated with whole-body subtotal bone mineral density (BMD) z-scores (p = 0.0385).

More children with NF1 had 25OHD concentrations <30 ng/mL, potentially because of increased pigmentation and/or decreased sunlight exposure. In contrast to adults, decreased 25OHD concentrations were not associated with neurofibromas, and there was no positive association between 25OHD and BMD.
Full text online

Vitamin D level similar in siblings

Vitamin D status and muscle function in children with neurofibromatosis type 1 (NF1)
J Musculoskelet Neuronal Interact. 2013 Mar;13(1):111-9.
Hockett CW1, Eelloo J, Huson SM, Roberts SA, Berry JL, Chaloner C, Rawer R, Mughal MZ.
1Department of Epidemiology, Colorado School of Public Health, Denver, CO, USA.

The aim of this cross-sectional study was to assess the vitamin D status and muscle function in children with NF1 compared with their unaffected siblings.

NF1 children between 5 and 18 years of age and who had at least one unaffected sibling were identified. Serum concentrations of 25-hydroxyvitamin D (25(OH)D), calcium, inorganic phosphate, alkaline phosphate, parathyroid hormone and 1,25-dihydroxyvitamin D were measured. The Leonardo Mechanography Ground Reaction Force Platform (GRFP) was used to measure EFI, jump power, force and height.

There was no significant difference in 25(OH)D between NF1 subjects and unaffected siblings. Relative jump power and force were found to be significantly different. The adjusted means (95% confidence limits) of non-NF1 and NF1 children for relative jump power (W/kg), controlling for body mass and age, were 37.31 (34.14, 40.49) and 32.51 (29.34, 35.68), respectively (P=0.054); and force (N/kg), controlling for body mass, age and gender, were 25.79 (24.28, 27.30) and 21.12 (19.61, 22.63), respectively (P<0.0001). Jumping parameters were not related to serum 25(OH)D.

There was no significant relationship between vitamin D status and NF1 status in children. NF1 children had significantly impaired jumping power and force, when compared to their unaffected siblings.

PMID: 23445921 full free text online

NF Idential Twins - 2019

YouTube Video
The normal looking twin has major memory problems


NF: 14 ng, controls 31 ng, number of dermal neurofibromas inversely proportional to Vitamin D

Vitamin D deficiency associated with number of neurofibromas in neurofibromatosis 1
J Med Genet. 2006 Oct; 43(10): 810–813.
Published online 2006 Mar 29. doi: 10.1136/jmg.2006.041095

M Lammert, J M Friedman, H J Roth, R E Friedrich, L Kluwe, D Atkins, T Schooler, and V‐F Mautner

Neurofibromatosis 1 (NF1) is a tumour suppressor gene syndrome characterized by multiple cutaneous and plexiform neurofibromas. Focal osseous abnormalities, short stature, and decreased bone mineral density are also frequent in people with NF1. We measured serum 25‐hydroxyvitamin D concentrations in 55 patients with NF1 and 58 healthy controls, and correlated the findings in the patients with NF1 with their estimated number of dermal neurofibromas. Geometric mean (SD) serum 25‐hydroxyvitamin D concentration was 14.0 (1.6) ng/mL among the patients with NF1 compared with 31.4 (1.7) ng/mL among healthy controls (p<<0.0001). The serum vitamin D concentration and number of dermal neurofibromas reported by patients with NF1 were inversely correlated (Spearman's ρ = −0.572, p<0.00001). The occurrence of low serum vitamin D concentrations in people with NF1, especially those with many dermal neurofibromas, may provide new pathogenic insights and have important therapeutic implications.
Full free text online
This paper was cited by 73 other studies as of March 2019

NF Clinical trial using 4,000 IU of Vitamin D

Vitamin D Supplementation for Adults With Neurofibromatosis Type 1 (NF1) (VitDBoneNF1)
NCT01968590 study completion date Oct 2020
Probably publish results in 2021 or 2022

One of the natural cures for NF is Vitamin D


NF has MORE seasonal variation in vitamin D levels than controls – wonder why

Differences of 25-hydroxyvitamin D3 concentrations in children and adults with neurofibromatosis type 1.
Clin Biochem. 2014 May;47(7-8):560-3. doi: 10.1016/j.clinbiochem.2014.02.02
Schnabel C1, Dahm S2, Streichert T3, Thierfelder W2, Kluwe L4, Mautner VF4.

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder, frequently associated with reduced bone mineral density. Serum 25-hydroxyvitamin D3 concentrations in NF1 adults are lower than in healthy controls in autumn respectively winter and are inversely correlated with the number of dermal neurofibromas. We investigated 25-hydroxyvitamin D3 levels in children and adults with neurofibromatosis type 1 in winter and summer and compared them to healthy controls to get more pathogenic insights in vitamin D3 metabolism in NF1 patients.

DESIGN AND METHODS: NF1 patients were clinically examined and serum 25-hydroxyvitamin D3 concentrations were measured in 58 NF1 adults and 46 children in winter as well as in summer and compared to sex-, age- and month-matched controls.

RESULTS: 52 adults suffered from 10 to 5000 dermal neurofibromas, whereas none of the children presented neurofibromas. 25-Hydroxyvitamin D3 increased from winter to summer (mean: 21.0 to 46.5nmol/l) in NF1 adults. This increase was even larger (p=0.0001) than in healthy controls (mean: 50.5 to 60.5nmol/l). However, there were no differences of 25-hydroxyvitamin D3 concentrations in NF1 children and healthy controls both in winter and in summer.

CONCLUSIONS: Only adults with NF1 showed lower 25-hydroxyvitamin D3 levels in winter and summer, which are unlikely due to impaired UV-dependent dermal synthesis, but rather might be caused by an accelerated catabolism.

PMID: 24613576

More dermal neurofibromas if poor Vitamin D Receptor - Oct 2018

Vitamin D receptor expression and serum 25(OH)D concentration inversely associates with burden of neurofibromas
European Journal of Cancer Prevention: October 05, 2018 -doi: 10.1097/CEJ.0000000000000467
Kluwe, Lana,b; Hagel, Christianc; Friedrich, Reinhard E.b; Schnabel, Claudiad; Schön, Gerharde; Mautner, Victora

Vitamin D and its receptor may play a role in preventing tumor development and progression. As such antineoplastic effects are expected to be weak and to act over long periods, conditions with increased tumor incidence, such as the neurofibromatosis type 1 (NF1), provide suitable study models. We previously found an inverse correlation of serum 25(OH)D concentration with number of neurofibromas in NF1.
Here we aim to further explore the role of the vitamin D receptor. A total of 141 adult NF1 patients were included in the study. For 101 of them, serum vitamin 25(OH)D data were available. From 87 patients, blood samples were obtained in PaxGene tubes containing a reagent to stabilize RNA immediately. mRNA of the vitamin D receptor (VDR) gene (coding for the vitamin D receptor) was measured by means of RT-PCR. Correlation of laboratory data with NF1-related tumors was statistically evaluated. Vitamin D receptor in NF1-tumors was examined by means of immunohistochemistry using an antibody against the vitamin D1 receptor.
The number of dermal neurofibromas was significantly inversely correlated with VDR mRNA level and with serum 25(OH)D concentration in NF1 patients. In contrast, plexiform neurofibroma and malignant peripheral nerve sheath tumor did not correlate with these two parameters. Immunostaining did not detect vitamin D receptor in NF1-tumors. Both vitamin D and its receptor may play a role in suppressing the development of neurofibromas. Sustaining 25(OH)D at an adequate level may contribute to controlling neurofibromas and possibly also other tumors. This is especially important for individuals with lower expression of VDR.

Vitamin D and VDR did not vary between NF1 and controls - 2015

Vitamin D Status and VDR Genotype in NF1 Patients: A Case-Control Study from Southern Brazil
 Download the PDF from VitaminDWiki

NIH overview of NF

NINDS Neurofibromatosis Information Page

NF skin pictures (and skin is only a small part of NF problems)

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Wikipedia on Rare Diseases

The European Organization for Rare Diseases (EURORDIS) estimates that as many as 5,000 to 7,000 distinct rare diseases exist, and as much as 6% to 8% of the population of the European Union is affected by one.[6] Only about 400 rare diseases have therapies and about 80% have a genetic component according to Rare Genomics Institute.

See also VitaminDWiki

Neurofibromatosis: chronological history and current issues - May 2013

 Download the PDF from VitaminDWiki

Intellectual problems, ADHD, autism spectrum disorder, and migraine are major neurological comorbidities in NF1 - Jan 2018

Pediatr Int. 2018 Jan;60(1):70-75. doi: 10.1111/ped.13388. Epub 2017 Oct 3

Vitamin D3 and UV treat Neurofibromatosis - 1 - 2017 book Chapter

 Download the PDF from VitaminDWiki

Attached files

ID Name Comment Uploaded Size Downloads
11702 Vitamin D3 and Neurofibromatosis Type 1.pdf admin 01 Apr, 2019 21:18 1.40 Mb 397
11691 Neurofibromatosis - chronological history.pdf admin 29 Mar, 2019 21:42 393.74 Kb 380
11681 VDR NF1.pdf admin 27 Mar, 2019 21:29 647.22 Kb 430
11680 NF1 identical twin.jpg admin 27 Mar, 2019 20:49 44.28 Kb 1343
5762 NF image 2.jpg admin 09 Aug, 2015 02:27 29.21 Kb 4956
5761 NF image 1.jpg admin 09 Aug, 2015 02:27 44.81 Kb 9651
5760 NF 5minutes.jpg admin 09 Aug, 2015 01:29 235.85 Kb 79212
5759 NF chart.jpg admin 09 Aug, 2015 01:20 29.97 Kb 6784
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