Revisiting the Association of Central Precocious Puberty with Neurovisceral Diseases owing to a Girl with Niemann-Pick Disease Type C.
This case highlights a possible link between Niemann-Pick Disease Type C and central precocious puberty, warranting further investigation.
Where it sits
this study against the rest of the leuprorelin corpusSummary and findings
An 8-year-old girl with Niemann-Pick Disease Type C developed central precocious puberty. She was treated with leuprolide acetate after being diagnosed with CPP. The case suggests a potential association between NP-C and CPP.
Abstract
Niemann-Pick type C disease (NP-C) is a rare neurovisceral disorder caused by mutations in the NPC1 or NPC2 genes. Clinical symptoms of NP-C can appear at any age. Here we report a case of a girl diagnosed with NP-C who subsequently developed central precocious puberty (CPP). To our knowledge, this association has not been described in the literature till now. An 8 year old girl was referred to the pediatric metabolism outpatient clinic due to poor school performance, behavioral changes and periventricular white matter signal changes observed on cranial magnetic resonance imaging (MRI). The physical examination revealed vertical supranuclear gaze palsy (VSGP) and splenomegaly. The patient was diagnosed NP-C through genetic analysis and was started miglustat treatment. The patient was also referred to the pediatric endocrinology outpatient clinic due to breast development (Tanner stage 3) and pubic hair (Tanner stage 3). Laboratory work up revealed normal basal serum LH (0. 2 U/L) and the LHRH test showed a LH value of 8.48 U/L and a peak LH/ FSH ratio of 2. 8 (>0.66). Pelvic ultrasonography revealed an uterine length of 45 mm and mean ovarian volume of 5. 5 mL, Leuprolide acetate was started and at the first year of follow-up the patient's height velocity was 0.4 SDS and Tanner's pubertal staging was 3. This case report highlights a potential association of NP-C with CPP and confirms the need for careful assessment of pubertal development in patients with white matter disease.
Background
Niemann-Pick Disease Type C (NP-C) is a rare genetic disorder characterized by neurovisceral symptoms due to mutations in the NPC1 or NPC2 genes. Central precocious puberty (CPP) is an early onset of puberty and has not been previously associated with NP-C. This study explores a novel potential link between NP-C and CPP, which could have implications for clinical monitoring of affected patients.
Methods
This is a case report of an 8-year-old girl diagnosed with NP-C through genetic analysis, presenting with symptoms such as poor school performance and behavioral changes. She was found to have central precocious puberty based on clinical and laboratory findings, including Tanner stage 3 breast and pubic hair development, and an elevated LH response to LHRH testing. Leuprolide acetate was administered as treatment.
Results
The primary observation was the development of CPP in a patient with NP-C, with a normal basal serum LH of 0.2 U/L and a peak LH/FSH ratio of 2.8 following LHRH testing. Pelvic ultrasonography showed a uterine length of 45 mm and mean ovarian volume of 5.5 mL. After one year of treatment with leuprolide acetate, the patient's height velocity was 0.4 SDS, and Tanner's pubertal staging remained at stage 3.
Interpretation
This case report suggests a potential but unproven association between NP-C and CPP, which has not been documented in the literature before. The findings are limited by the single-case nature of the report, and further research is needed to establish a causal relationship. The clinical significance of this association remains uncertain, and clinicians should be cautious in interpreting these findings.
Key findings
- 8-year-old girl with NP-C and CPP
- Normal basal serum LH of 0.2 U/L
- LHRH test showed LH value of 8.48 U/L
- Peak LH/FSH ratio of 2.8
- Uterine length of 45 mm and mean ovarian volume of 5.5 mL
- Height velocity 0.4 SDS at 1-year follow-up
Limitations
- Single case report
- No established association in broader studies
- Limited generalizability
- No long-term follow-up data