Long-term normalization of cognitive and psychopathological alterations in a juvenile Niemann–Pick type C case

Niemann–Pick type C (NP-C) disease is a neurovisceral atypical lysosomal lipid storage disorder with a poor prognosis. We present the 5-year neuropsychological follow-up of a patient with juvenile onset NP-C, spanning the pre-diagnostic stage to the period after treatment with miglustat (Actelion Pharmaceuticals Inc., CA, US). In the initial stages of the disease, the patient presented behavioral dysexecutive symptoms resembling those frequently observed in adult-onset forms and frontotemporal dementia, which frequently makes early diagnosis difficult in children. After 4 years of treatment, the impaired cognitive function and behavioral dysexecutive syndrome had been completely reversed. The variability of NP-C disease makes early diagnosis challenging. Evaluations of long-term neuropsychological development can help diagnose this neurodegenerative disease and document its progression.

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Neuropsychological and electrophysiological long-term follow-up in the adult form of Niemann-Pick disease type C

Clinical Neurophysiology ◽

10.1016/j.clinph.2018.09.083 ◽

2019 ◽

Vol 130 (1) ◽

pp. e13-e14

Author(s):

S. Tozza ◽

R. Dubbioso ◽

R. Iodice ◽

A. Topa ◽

M. Esposito ◽

...

Keyword(s):

Disease Type ◽

Adult Form ◽

Niemann Pick Disease ◽

Long Term Follow Up ◽

Type C ◽

Niemann Pick ◽

Pick Disease

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Extensive Limb Lengthening for Achondroplasia and Hypochondroplasia

10.20944/preprints202105.0268.v1 ◽

2021 ◽

Author(s):

Dror Paley

Keyword(s):

Skeletal Maturity ◽

Limb Lengthening ◽

Adult Onset ◽

Juvenile Onset ◽

Normal Height ◽

Height Range ◽

Long Term Follow Up ◽

Males And Females

Extensive limb lengthening (ELL) was completed in 75 patients: 66 achondroplasia and 9 hypochondroplasia. The average lengthening was 27cm for achondroplasia (12-40cm) and 17cm for hypochondroplasia (range 10-25cm). There were 48 females and 27 males. Lengthening was done either by 2-segment (14 patients; both tibias and/or both femurs) or by serial 4-segment lengthenings (64 patients; both femurs and tibias same time). Most patients also had bilateral humeral lengthening. Lengthenings were either juvenile-onset (31), adolescent-onset (38) or adult-onset (6). The average age at final follow-up was 26 years old (range 17-43 years). There were few permanent sequelae of complications. The most serious was one paraparesis. All patients returned to activities of normal living and only one was made worse by the surgery (paraparesis). This is the first study to show that ELL can lead to increase of height into the normal height range. Previous studies showed mean increases of height of up to 20cm, while this study consistently showed an average increase of 30 cm (range 15-40cm) for juvenile-onset and increase of 26cm (range 15-30cm) for adolescent-onset. This results in lower normal height at skeletal maturity for males and females. The adult-onset had a mean increase of 16.8 (range 12-22cm). This long-term follow-up study shows ELL can be done safely even with large lengthenings and that 4-segment lengthening may offer advantages over 2-segment lengthening. While the majority of cases were performed using external fixation, implantable limb lengthening promises to be an excellent alternative and perhaps an improvement.

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Faculty Opinions recommendation of Long term follow-up to evaluate the efficacy of miglustat treatment in Italian patients with Niemann-Pick disease type C.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727681014.793542547 ◽

2018 ◽

Author(s):

Barbara Borroni

Keyword(s):

Disease Type ◽

Niemann Pick Disease ◽

Long Term Follow Up ◽

Type C ◽

Niemann Pick ◽

Pick Disease

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Adult-Onset Niemann–Pick Disease Type C: Rapid Treatment Initiation Advised but Early Diagnosis Remains Difficult

Frontiers in Neurology ◽

10.3389/fneur.2017.00108 ◽

2017 ◽

Vol 8 ◽

Cited By ~ 3

Author(s):

Tobias Piroth ◽

Kai Boelmans ◽

Florian Amtage ◽

Michel Rijntjes ◽

Anna Wierciochin ◽

...

Keyword(s):

Early Diagnosis ◽

Treatment Initiation ◽

Disease Type ◽

Adult Onset ◽

Niemann Pick Disease ◽

Type C ◽

Niemann Pick ◽

Pick Disease ◽

Rapid Treatment

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Comparative Analysis of Cerebral Magnetic Resonance Imaging Changes in Nontreated Infantile, Juvenile and Adult Patients with Niemann-Pick Disease Type C

Neuropediatrics ◽

10.1055/s-0039-1698451 ◽

2019 ◽

Vol 51 (01) ◽

pp. 037-044 ◽

Cited By ~ 2

Author(s):

Janina Gburek-Augustat ◽

Samuel Groeschel ◽

Jan Kern ◽

Stefanie Beck-Woedl ◽

Jennifer Just ◽

...

Keyword(s):

White Matter ◽

Scoring System ◽

Disease Course ◽

Adult Onset ◽

Juvenile Onset ◽

White Matter Changes ◽

Cerebral Magnetic Resonance Imaging ◽

Cerebral Mri ◽

Type C ◽

Niemann Pick

Abstract Aim The study aims to describe cerebral MRI in different onset forms of Niemann-Pick type C (NPC). Systematic MRI analyses in this rare lysosomal storage disease are lacking in the infantile and juvenile onset forms. Methods Thirty-two cerebral MRI scans from 19 patients with NPC were assessed using a newly established and validated scoring system which addresses white matter changes and supratentorial versus infratentorial atrophy. Results Seven scans were from six NPC patients with early infantile onset (<2 years of age), six scans were from three patients with late infantile onset (2–6 years), six scans from four with juvenile onset (6–15 years), and 13 from six with adult onset (>15 years). While supratentorial atrophy was the leading sign in the infantile groups, the juvenile and adult forms were characterized by both, infra- and supratentorial atrophy. White matter changes were found in nearly every patient; they increased with the disease duration in the earlier forms and were prominent in the later forms already early in the disease course. Conclusion This is the first systematic and comparative MRI analysis in the different onset groups of NPC using a scoring system. Early during disease course, MRI showed different patterns in infantile compared with juvenile and adult onset NPC patients, for example, only supratentorial atrophy in juvenile versus global atrophy in adult onset patients. MRI changes provide an additional, early biomarker for NPC.

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Long term follow-up to evaluate the efficacy of miglustat treatment in Italian patients with Niemann-Pick disease type C

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-015-0240-y ◽

2015 ◽

Vol 10 (1) ◽

pp. 22 ◽

Cited By ~ 33

Author(s):

Simona Fecarotta ◽

Alfonso Romano ◽

Roberto Della Casa ◽

Ennio Del Giudice ◽

Diana Bruschini ◽

...

Keyword(s):

Disease Type ◽

Niemann Pick Disease ◽

Long Term Follow Up ◽

Type C ◽

Niemann Pick ◽

Pick Disease

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Extensive Limb Lengthening for Achondroplasia and Hypochondroplasia

Children ◽

10.3390/children8070540 ◽

2021 ◽

Vol 8 (7) ◽

pp. 540

Author(s):

Dror Paley

Keyword(s):

Skeletal Maturity ◽

Limb Lengthening ◽

Adult Onset ◽

Juvenile Onset ◽

Normal Height ◽

Height Range ◽

Humeral Lengthening ◽

Long Term Follow Up

Extensive limb lengthening (ELL) was completed in 75 patients: 66 achondroplasia and 9 hypochondroplasia. The average lengthening was 27 cm for achondroplasia (12–40 cm) and 17 cm for hypochondroplasia (range 10–25 cm). There were 48 females and 27 males. Lengthening was done either by 2-segment (14 patients; both tibias and/or both femurs) or by 4-segment lengthenings (64 patients; both femurs and tibias at the same time). Most patients also had bilateral humeral lengthening. Patients had 2 or 3 lower limb lengthenings and one humeral lengthening. Lengthenings were either juvenile-onset (31), adolescent-onset (38) or adult-onset (6). The average age at final follow-up was 26 years old (range 17–43 years). There were few permanent sequelae of complications. The most serious was one paraparesis. All patients returned to activities of normal living and only one was made worse by the surgery (paraparesis). This is the first study to show that ELL can lead to an increase of height into the normal height range. Previous studies showed mean increases of height of up to 20 cm, while this study consistently showed an average increase of 30 cm (range 15–40 cm) for juvenile-onset and mean increase of 26 cm (range 15–30 cm) for adolescent-onset. This results in low normal height at skeletal maturity for males and females. The adult-onset had a mean increase of 16.8 (range 12–22 cm). This long-term follow-up study shows that ELL can be done safely even with large lengthenings and that 4-segment lengthening may offer advantages over 2-segment lengthening. While all but the more recent cases were performed using external fixation, implantable limb lengthening promises to be an excellent alternative and perhaps an improvement.

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One repeated transplantation of allogeneic umbilical cord mesenchymal stromal cells in type 1 diabetes: an open parallel controlled clinical study

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02417-3 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Jing Lu ◽

Shan-mei Shen ◽

Qing Ling ◽

Bin Wang ◽

Li-rong Li ◽

...

Keyword(s):

Type 1 Diabetes ◽

Stromal Cells ◽

Treated Group ◽

Control Group ◽

Adult Onset ◽

Β Cell ◽

Juvenile Onset ◽

C Peptide

Abstract Background The preservation or restoration of β cell function in type 1 diabetes (T1D) remains as an attractive and challengeable therapeutic target. Mesenchymal stromal cells (MSCs) are multipotent cells with high capacity of immunoregulation, which emerged as a promising cell-based therapy for many immune disorders. The objective of this study was to examine the efficacy and safety of one repeated transplantation of allogeneic MSCs in individuals with T1D. Methods This was a nonrandomized, open-label, parallel-armed prospective study. MSCs were isolated from umbilical cord (UC) of healthy donors. Fifty-three participants including 33 adult-onset (≥ 18 years) and 20 juvenile-onset T1D were enrolled. Twenty-seven subjects (MSC-treated group) received an initial systemic infusion of allogeneic UC-MSCs, followed by a repeat course at 3 months, whereas the control group (n = 26) only received standard care based on intensive insulin therapy. Data at 1-year follow-up was reported in this study. The primary endpoint was clinical remission defined as a 10% increase from baseline in the level of fasting and/or postprandial C-peptide. The secondary endpoints included side effects, serum levels of HbA1c, changes in fasting and postprandial C-peptide, and daily insulin doses. Results After 1-year follow-up, 40.7% subjects in MSC-treated group achieved the primary endpoint, significantly higher than that in the control arm. Three subjects in MSC-treated group, in contrast to none in control group, achieved insulin independence and maintained insulin free for 3 to 12 months. Among the adult-onset T1D, the percent change of postprandial C-peptide was significantly increased in MSC-treated group than in the control group. However, changes in fasting or postprandial C-peptide were not significantly different between groups among the juvenile-onset T1D. Multivariable logistic regression assay indicated that lower fasting C-peptide and higher dose of UC-MSC correlated with achievement of clinical remission after transplantation. No severe side effects were observed. Conclusion One repeated intravenous dose of allogeneic UC-MSCs is safe in people with recent-onset T1D and may result in better islet β cell preservation during the first year after diagnosis compared to standard treatment alone. Trial registration ChiCTR2100045434. Registered on April 15, 2021—retrospectively registered, http://www.chictr.org.cn/

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