Glycoprotein non-metastatic protein B (GPNMB) plasma values in patients with chronic visceral acid sphingomyelinase deficiency.

Acid sphingomyelinase deficiency (ASMD) is a rare LSD characterized by lysosomal accumulation of sphingomyelin, primarily in macrophages. With the recent availability of enzyme replacement therapy, the need for biomarkers to assess severity of disease has increased. Glycoprotein non-metastatic protein B (GPNMB) plasma levels were demonstrated to be elevated in Gaucher disease. Given the similarities between Gaucher disease and ASMD, the hypothesis was that GPNMB might be a potential biochemical marker for ASMD as well. Plasma samples of ASMD patients were analyzed and GPNMB plasma levels were compared to those of healthy volunteers. Visceral disease severity was classified as severe when splenic, hepatic and pulmonary manifestations were all present and as mild to moderate if this was not the case. Median GPNMB levels in 67 samples of 19 ASMD patients were 185 ng/ml (range 70-811 ng/ml) and were increased compared to 10 healthy controls (median 36 ng/ml, range 9-175 ng/ml, p < 0.001). Median plasma GPNMB levels of ASMD patients with mild to moderate visceral disease compared to patients with severe visceral disease differed significantly and did not overlap (respectively 109 ng/ml, range 70-304 ng/ml and 325 ng/ml, range 165-811 ng/ml, p < 0.001). Correlations with other biochemical markers of ASMD (i.e. chitotriosidase activity, CCL18 and lysosphingomyelin, respectively R = 0.28, p = 0.270; R = 0.34, p = 0.180; R = 0.39, p = 0.100) and clinical parameters (i.e. spleen volume, liver volume, diffusion capacity and forced vital capacity, respectively R = 0.59, p = 0.061, R = 0.5, p = 0.100, R = 0.065, p = 0.810, R = -0.38, p = 0.160) could not be established within this study. The results of this study suggest that GPNMB might be suitable as a biomarker of visceral disease severity in ASMD. Correlations between GPNMB and biochemical or clinical markers of ASMD and response to therapy have to be studied in a larger cohort.

Olipudase alfa enzyme replacement therapy for acid sphingomyelinase deficiency (ASMD): sustained improvements in clinical outcomes after 6.5 years of treatment in adults.

BACKGROUND: Enzyme replacement therapy with olipudase alfa, a recombinant human acid sphingomyelinase (rhASM), is indicated for non-central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in children and adults. An ongoing, open-label, long-term study (NCT02004704) assessed the safety and efficacy of olipudase alfa in 5 adults with ASMD. RESULTS: After 6.5 years of treatment, there were no discontinuations, no olipudase-alfa-related serious adverse events, and no new safety signals compared to earlier assessments. Most treatment-emergent adverse events were mild in intensity (1742/1766, 98.6%). Among treatment-related adverse events (n = 657), more than half were considered infusion-associated reactions (n = 403, 61.3%) such as headache, nausea, abdominal pain, arthralgia, pyrexia, and fatigue. No patient developed neutralizing anti-drug antibodies to cellular uptake, and there were no clinically significant adverse changes in vital signs, hematology, or cardiac safety parameters. Improvements (decreases) in spleen and liver volumes progressed through 6.5 years (mean changes from baseline of -59.5% and -43.7%, respectively). There was a mean increase in diffusing capacity of the lung for carbon monoxide from baseline of 55.3%, accompanied by improvements in interstitial lung disease parameters. Lipid profiles at baseline indicated dyslipidemia. All patients had sustained decreases in pro-atherogenic lipid levels and increases in anti-atherogenic lipid levels following olipudase alfa treatment. CONCLUSIONS: Olipudase alfa is the first disease-specific treatment for ASMD. This study demonstrates that long-term treatment with olipudase alfa is well-tolerated and is associated with sustained improvements in relevant disease clinical measures. NCT02004704 registered 26 November 2013, https://clinicaltrials.gov/ct2/show/NCT02004704?term=NCT02004704&draw=2&rank=1 .

Three-years misdiagnosis of Niemann Pick disease type B with novel mutations in SMPD1 gene as Budd-Chiari syndrome.

BACKGROUND: The chronic visceral subtype of acid sphingomyelinase deficiency, commonly known as Niemann Pick disease type B (NPDB), is a relatively rare autosomal recessive genetic disorder that is caused by mutations in the SMPD1 gene. NPDB with sea-blue histiocytes (SBH) clinically mimics Budd-Chiari syndrome (BCS), as it lacks specific clinical characteristics. This makes its diagnosis difficult. CASE PRESENTATION: Here, we report a case of NPDB with SBH that was misdiagnosed as BCS for three years. A 20-year-old female with abdominal distension, hepatosplenomegaly, and haematological anomalies was initially diagnosed with BCS based on her imaging finding of a thin hepatic vein and rapid blood flow at the confluence of the hepatic vein and inferior vena cava. Her bone marrow cytology found sea-blue histiocytes. Liver biopsy showed foamy cytoplasm in hepatocytes surrounded by numerous Kupffer cells. Sequencing analysis of the SMPD1 gene led to the finding of two missense mutations in the heterozygous state: C.829 T > C (p.Trp277Arg) in exon 2 (novel) and c.1805G > A (p.Arg602His) in exon 6 (already described). These findings established the diagnosis of NPDB. CONCLUSION: The patient presented with hepatosplenomegaly, haematological anomalies, and dyslipidaemia. Thus, NPDB should be considered following the exclusion of related diseases. The diagnosis of NPDB was suspected by clinical symptoms and routine laboratory tests and was confirmed by liver biopsy and gene sequencing. The novel mutation c.829 T > C in exon 2 of the SMPD1 gene has never been reported and needs to be further investigated.

Spontaneous splenic rupture as the first clinical manifestation of Niemann-Pick disease type B: A case report and review of the literature.

Splenomegaly is the most common phenotype for Niemann-Pick disease type B (NPD-B), an autosomal recessive lipid storage disease caused by deficiency of the lysosomal enzyme acid sphingomyelinase. Although a spleen of massive volume is common in NPD-B, splenic rupture in this disease is rarely reported. We describe a patient with NPD-B who initially presented with spontaneous splenic rupture. Microscopic examination of the spleen specimen revealed expansion of the red pulp by abundant foamy histiocytes. A literature review revealed that splenic rupture resulting from latent splenomegaly may occur in middle adulthood in a mild form of NPD-B associated with SMPD1 variants of lower pathogenicity. We suggest that unexplained splenomegaly or splenic rupture should raise the possibility of a lysosomal storage disease, including NPD. For patients with NPD-B, spleen size should be evaluated periodically, and the risk of splenic rupture should always be considered.

Atherogenic lipid profile in patients with Niemann-Pick disease type B: What treatment strategies?

Niemann-Pick disease (NPD) type A and type B are part of the spectrum disease of the acid sphingomyelinase deficiency (ASMD). Plasma lipid abnormalities are frequently associated with both NPD-A and NPD-B, and include decreased high-density lipoprotein cholesterol (HDL-C), increased low-density lipoprotein cholesterol (LDL-C), and hypertriglyceridemia. The atherogenic lipid profile has been associated to early atherosclerotic vascular disease and coronary artery disease in NPD-B patients. Thus, early treatment of dyslipidemia in these patients is advisable. We present here a pediatric case of NPD-B with an atherogenic lipid profile not responding to lifestyle changes, low fat diet, and daily supplementation with plant sterols. We reviewed the existing literature about the treatment strategies for dyslipidemia in ASMD patients, with a special focus on the pediatric age. Finally, we speculated on the mechanisms underlying dyslipidemia in this disorder. The clinical experiences in lipid-lowering strategies in NPD-B patients are limited, in particular in the pediatric age. Olipudase alfa appears as the most promising candidate for improving lipid profile. Since olipudase alfa is not yet approved and, due to its costs, it will probably not be available for all patients worldwide, further research is needed to broaden our knowledge on this clinical need and to evaluate the efficacy and the long-term effects of lipid-lowering agents in ASMD patients. A deep understanding of the pathophysiology of dyslipidemia in ASMD may promote the identification of new targets and support the identification of new therapeutic strategies.

The influence of hematopoietic stem cell transplant on pulmonary involvement in pediatric type B Niemann-Pick disease: high resolution CT findings / 中华放射学杂志

Objective:To analyze the pulmonary high resolution CT (HRCT) images before and after hematopoietic stem cell transplantation (HSCT) in 6 children with Niemann-Pick disease(NPD) type B, and to investigate the effect of HSCT on lung lesions.Methods:Data of 6 children who were diagnosed with NPD type B and underwent HSCT treatment in Children′s Hospital Affiliated to Capital Institute of Pediatric from March 2019 to June 2021 were retrospectively enrolled, including 5 males and 1 female, with ages ranging from 1 year and 2 months to 5 years, and a median age of 2 years and 1month. The follow-up time of HRCT after HSCT was 7-20.5 months, the median time was 5 months, and the number of follow-up was 2-7 per patients, a total of 27 times. The pulmonary lesions (including interstitial lung disease, airway lesions and alveolar lesions) on aortic arch level, tracheal carina level and right diaphragmatic surface level were evaluated and scored respectively by two experienced pediatric radiologists, and the average score between them would be the final score. The Kruskal-Wallis H test was used to compare the scores of the three kinds of lung lesions before HSCT. The linear regression method was used to analyze the impact of HSCT duration on the degree of different lesions. To control possible confounding factors in the study, a generalized linear mixed model was used to evaluate the effects of HSCT duration, age, gender and whether co-infection on different types of lesions after HSCT. Results:Before HSCT treatment, all of the 6 children had different degree of airway, interstitial and alveolar lesions, with a median score of 3.0, 14.0 and 5.8 points, respectively (χ2=11.95, P=0.003). Interstitial disease was the most extensive and serious lesion among those three pulmonary involvements in pediatric NPD type B. After HSCT treatment, the scores of interstitial and airway lesions in all of the 6 children reduced, in varying degree, with the increase of time after HSCT. Except case 4, the alveolar lesion in 5 patients also showed a decreasing trend over time. The linear regression equation between the score of airway, interstitial, alveolar lesions and the HSCT duration was: airway lesion, Y=1.94-0.15X; interstitial lesion, Y=12.73-0.78X; and alveolar lesion, Y=3.31-0.27X. The results of the generalized linear mixed model showed that the main effect of HSCT duration significantly affected on the three kinds of lung lesions, and the scores of interstitial lesions, airway lesions and alveolar lesions were decreased by 0.688, 0.245, and 0.338 points for each 1 month increase of HSCT duration (all P<0.05). The alveolar lesion score decreased by 1.135 points for each 1 year increase in age at presentation ( P=0.012). The main effects of gender and co-infection were not statistically significant in all of the pulmonary lesions (both P>0.05). Conclusion:HSCT alleviates pulmonary lesions of children with NPD type B significantly and consistently, with interstitial lesions were the most prominent.

Bilateral Cystic Bronchiectasis as Novel Phenotype of Niemann-Pick Disease Type B Successfully Treated With Double Lung Transplantation.

Niemann-Pick Disease type B (NPDB) is a rare autosomal recessive disease belonging to the family of lysosomal storage disorders. NPDB is caused by mutations of sphingomyelin phosphodiesterase 1 gene (SMPD1) and is characterized by hepatosplenomegaly, interstitial lung disease, recurrent pulmonary infections, and neurologic disorders. Bronchiectasis are atypical. Until now, only three cases of lung transplantation for severe respiratory impairment have been reported. We describe a case of NPDB that was diagnosed after lung transplantation for cystic bronchiectasis. In 2016, a 31-year-old woman who was experiencing hypoxemic respiratory failure and recurrent pulmonary infections due to cystic bronchiectasis received a double-lung-transplantation. Histopathologic study on removed lungs revealed clusters of CD68 foamy lipid-laden macrophages with concentric and palisade arrangement, compatible with the diagnosis of NPDB, which was confirmed after SMPD1 genetic sequencing. Twenty-three months after transplantation, allograft function is stable (FEV1 was 100% of best-FEV1). The singularity of this case lies in the presence of bronchiectasis, which is an unprecedently described phenotype of NPDB. This finding was accompanied by the detection of a novel SMPD1 mutation (p.Ala46=) of uncertain meaning.

Prospective study of the natural history of chronic acid sphingomyelinase deficiency in children and adults: eleven years of observation.

BACKGROUND: Acid sphingomyelinase deficiency (ASMD) (also known as Niemann-Pick disease types A and B) is a rare and debilitating lysosomal storage disorder. This prospective, multi-center, multinational longitudinal study aimed to characterize the clinical features of chronic forms of ASMD and disease burden over time in children and adults. RESULTS: Fifty-nine patients (31 males/28 females) ranging in age from 7 to 64 years with chronic ASMD types A/B and B and at least two disease symptoms participated from 5 countries. Disease characteristics were assessed at baseline, after 1 year, and at the final visit (ranging from 4.5 to 11 years). Thirty patients (51%) were < 18 years at baseline (median age 12 years), and 29 were adults (median age 32 years). Overall, 32/59 patients completed the final visit, 9 died, 9 discontinued, and 9 were lost to follow up. Common clinical characteristics that tended to worsen gradually with time were splenomegaly, hepatomegaly, interstitial lung disease, lung diffusion capacity (DLCO), and dyslipidemia. Spleen volumes ranged from 4 to 29 multiples of normal at baseline, and splenomegaly was moderate or severe in 86%, 83%, and 90% of individuals at baseline, year 1, and final visits, respectively. The proportion of all individuals with interstitial lung disease was 66% (39/59) at baseline and 78% (25/32) at the final visit, while median % predicted DLCO decreased by > 10% from baseline to the final visit. Nine patients died (15%), eight of causes related to ASMD (most commonly pneumonia); of these eight patients, five (63%) had symptom onset at or before age 2. Overall, six of the nine deaths occurred before age 50 with three occurring before age 20. Individuals with either severe splenomegaly or prior splenectomy were ten times more likely to have died during the follow-up period than those with smaller or intact spleens (odds ratio 10.29, 95% CI 1.7, 62.7). Most children had growth deficits that persisted into adulthood. CONCLUSIONS: This study provides important information about the natural history of chronic ASMD and provides a longitudinal view of the spectrum of disease manifestations and major morbidities in children and adults and supports the selection of clinically meaningful endpoints in therapeutic trials.

Long-term efficacy of olipudase alfa in adults with acid sphingomyelinase deficiency (ASMD): Further clearance of hepatic sphingomyelin is associated with additional improvements in pro- and anti-atherogenic lipid profiles after 42 months of treatment.

The liver is a major site of lipoprotein synthesis and metabolism. Liver manifestations of chronic visceral ASMD include hepatomegaly, fibrosis, elevated liver enzymes and a pro-atherogenic lipid profile. Measurements of sphingomyelin (SM) levels in liver biopsies and lyso-SM in plasma were used as pharmacodynamic biomarkers. Five adult patients with chronic visceral ASMD were enrolled in a 26-week phase 1b trial of enzyme replacement therapy (ERT) with olipudase alfa (NCT01722526) followed by an ongoing long-term extension study (NCT02004704). We compare the changes in hepatic SM levels, plasma lyso-SM, and lipoprotein profiles after 42 months of treatment. Progressive clearance of histologic SM storage was observed throughout the trial, along with similar reductions in plasma lyso-SM. Improvements in liver enzymes were observed at 6 months and remained stable at 42 months. Progressive reductions from baseline in pro-atherogenic lipid profiles (total cholesterol, LDL-C, VLDL-C, triglycerides) were observed at month 6 and 42. Conversely, there were progressive increases in anti-atherogenic markers, HDL-C and apolipoprotein A-I, with HDL-C increases up to 200% over baseline levels after 42 months of treatment. These data demonstrate that hepatic clearance of SM during olipudase alfa treatment over 42 months is associated with overall improvements in the lipid profiles of ASMD patients. The clinical relevance of these findings needs to be determined in the future, but we speculate that these improvements may reduce the risk for liver cirrhosis and cardiovascular disease. Trial registration: Clintrials.gov trial registration # NCT01722526.

Niemann-Pick disease type-B: a unique case report with compound heterozygosity and complicated lipid management.

BACKGROUND: Niemann-Pick disease (NPD) is a rare autosomal recessive hereditary disease characterized by deficient activity of acid sphingomyelinase. CASE PRESENTATION: We present a case of NPD type B with a unique compound heterozygosity for SMPD1 (NM_000543.4:c.[84delC];[96G > A]) in which both mutations that induce an early stop codon are located before the second in-frame initiation codon. The clinical presentation of the patient is compatible with NPD type B. She was initially diagnosed of Gaucher Disease, but her altered lipid profile led to a clinical suspicion of NPD. Combined high doses of atorvastatin and ezetimibe were given to treat the severe hypercholesterolemia. CONCLUSIONS: The pharmacological management of the lipid profile in these patients is important. A unique compound mutation in SMPD1 gene is described.

Biochemical and imaging parameters in acid sphingomyelinase deficiency: Potential utility as biomarkers.

Acid Sphingomyelinase Deficiency (ASMD), or Niemann-Pick type A/B disease, is a rare lipid storage disorder leading to accumulation of sphingomyelin and its precursors primarily in macrophages. The disease has a broad phenotypic spectrum ranging from a fatal infantile form with severe neurological involvement (the infantile neurovisceral type) to a primarily visceral form with different degrees of pulmonary, liver, spleen and skeletal involvement (the chronic visceral type). With the upcoming possibility of treatment with enzyme replacement therapy, the need for biomarkers that predict or reflect disease progression has increased. Biomarkers should be validated for their use as surrogate markers of clinically relevant endpoints. In this review, clinically important endpoints as well as biochemical and imaging markers of ASMD are discussed and potential new biomarkers are identified. We suggest as the most promising biomarkers that may function as surrogate endpoints in the future: diffusion capacity measured by spirometry, spleen volume, platelet count, low-density lipoprotein cholesterol, liver fibrosis measured with a fibroscan, lysosphingomyelin and walked distance in six minutes. Currently, no biomarkers have been validated. Several plasma markers of lipid-laden cells, fibrosis or inflammation are of high potential as biomarkers and deserve further study. Based upon current guidelines for biomarkers, recommendations for the validation process are provided.

Pulmonary involvement in selected lysosomal storage diseases and the impact of enzyme replacement therapy: A state-of-the art review.

Lysosomal storage disorders (LSDs) are multisystemic, progressive and clinically very heterogeneous. Respiratory complications are not regarded as the principal problems of LSDs, but significantly impact morbidity. In this review, we focus on pulmonary complications observed in late-onset LSDs, their milder forms that are recognised in adulthood. We also discuss the effects of enzyme replacement therapy (ERT) on the respiratory system in patients with particular LSDs. We searched the PubMed database, retrieving research papers on pulmonary complications of LSDs currently treated with ERT (the conditions are abbreviated GD3; NPDB; LOPD; MPS I, II, IVA, VI; and FD) and the effects of such treatment. Although some studies indicated that ERT was helpful in terms of reducing chest computed tomography abnormalities, infection frequency and organomegaly, the data are not conclusive, and the mechanism of action of ERT in the respiratory system remains unclear for some LSDs including late-onset Pompe disease and Gaucher disease type III. The optimal timing of treatment for pre-symptomatic or symptomatic patients, treatment duration and whether such treatment modulates inflammation (as has been suggested in patients with Fabry disease), remain to be explored.

Hematopoietic stem cell transplantation in Niemann-Pick disease type B monitored by chitotriosidase activity.

Here, we report a patient with Niemann-Pick disease type B, with early severe onset of disease and pulmonary involvement, treated with hematopoietic stem cell transplant (HSCT) from a bone marrow matched unrelated donor. We confirm that HSCT is feasible and potentially beneficial for patients with severe phenotype. Noteworthy, we discussed the potential usefulness of the activity of peripheral chitotriosidase for the longitudinal evaluation of HSCT success and effectiveness.

Limited benefits of presymptomatic cord blood transplantation in neurovisceral acid sphingomyelinase deficiency (ASMD) intermediate type.

Acid sphingomyelinase (ASM) deficient Niemann-Pick disease is a lysosomal storage disorder resulting from mutations in the SMPD1 gene. The clinical spectrum distinguishes a severe infantile neurological form (type A), a non-neurological visceral form (type B) and a rare intermediate neurovisceral form. We report the first case of presymptomatic cord blood transplantation in a child with the intermediate type of ASM deficiency due to a homozygous Tyr369Cys mutation, whose affected elder brother had developed neurodevelopmental delay from 19 months of age, and had died from severe visceral complications at the age of 3. In the transplanted propositus, neurological deterioration became evident by 4 years of age; the child was alive at age 8, although severely disabled. Whereas the transplant prevented visceral progression and early death, it could only delay neurocognitive deterioration.

[Acid sphingomyelinase deficiency (Niemann-Pick disease type B) in adulthood: A retrospective multicentric study of 28 adult cases]. / Déficit en sphingomyélinase acide (maladie de Niemann-Pick B) : une étude rétrospective multicentrique de 28 patients adultes.

INTRODUCTION: Acid sphingomyelinase deficiency (ASMD) is an autosomal recessive disease with a clinical spectrum ranging from a neurovisceral infantile form (Niemann-Pick disease type A) to a chronic visceral form also encountered in adults (Niemann-Pick disease type B, NP-B). METHODS: Retrospective multicentric analysis of French adult patients with ASMD over the period 1985-March 2015. Clinical, biological, and imaging data were analyzed. RESULTS: Twenty-eight patients (19 males, 9 females) were analyzed. Diagnosis was made before the age of 10 years in 16 cases. Main symptoms at diagnosis were spleen/liver enlargement and interstitial lung disease. Biological abnormalities included: thrombocytopenia (platelet count <150 000/mm3) in 24 cases including 4 patients with platelet count <60 000/mm3, constantly low high-density lipoprotein (HDL) cholesterol, polyclonal hypergammaglobulinemia (n=6), monoclonal gammopathy of unknown significance (n=5), normal prothrombin level discordant with low factor V (n=5), elevated chitotriosidase level (n=11). The diagnosis was confirmed in all cases by deficient acid sphingomyelinase enzyme activity. SMPD1 gene sequencing was performed in 25 cases. The frequent p.R610del mutation was largely predominant, constituting 62% of the non-related alleles. During the follow-up period, three patients died before 50 years of age from cirrhosis, heart failure and lung insufficiency, respectively. CONCLUSION: ASMD in adulthood (NP-B) associates spleen/liver enlargement and interstitial lung disease. Early diagnosis and appropriate management are essential for reducing the risk of complications, improving quality of life, and avoiding inappropriate procedures such as splenectomy. To date, only symptomatic therapy is available. A phase 2/3 therapeutic trial with IV infusion of recombinant enzyme is on-going.

Successful within-patient dose escalation of olipudase alfa in acid sphingomyelinase deficiency.

BACKGROUND: Olipudase alfa, a recombinant human acid sphingomyelinase (rhASM), is an investigational enzyme replacement therapy (ERT) for patients with ASM deficiency [ASMD; Niemann-Pick Disease (NPD) A and B]. This open-label phase 1b study assessed the safety and tolerability of olipudase alfa using within-patient dose escalation to gradually debulk accumulated sphingomyelin and mitigate the rapid production of metabolites, which can be toxic. Secondary objectives were pharmacokinetics, pharmacodynamics, and exploratory efficacy. METHODS: Five adults with nonneuronopathic ASMD (NPD B) received escalating doses (0.1 to 3.0 mg/kg) of olipudase alfa intravenously every 2 weeks for 26 weeks. RESULTS: All patients successfully reached 3.0mg/kg without serious or severe adverse events. One patient repeated a dose (2.0 mg/kg) and another had a temporary dose reduction (1.0 to 0.6 mg/kg). Most adverse events (97%) were mild and all resolved without sequelae. The most common adverse events were headache, arthralgia, nausea and abdominal pain. Two patients experienced single acute phase reactions. No patient developed hypersensitivity or anti-olipudase alfa antibodies. The mean circulating half-life of olipudase alfa ranged from 20.9 to 23.4h across doses without accumulation. Ceramide, a sphingomyelin catabolite, rose transiently in plasma after each dose, but decreased over time. Reductions in sphingomyelin storage, spleen and liver volumes, and serum chitotriosidase activity, as well as improvements in infiltrative lung disease, lipid profiles, platelet counts, and quality of life assessments, were observed. CONCLUSIONS: This study provides proof-of-concept for the safety and efficacy of within-patient dose escalation of olipudase alfa in patients with nonneuronopathic ASMD.

Generalized Lichen Nitidus in a boy with Niemann-Pick disease type B / Liquen nitido generalizado em paciente com doenca de Niemann-Pick tipo B

Generalized lichen nitidus is an uncommon chronic inflammatory dermatosis with very characteristic histological findings. Its pathogenesis is still unclear; very rarely it has been associated with genetic disorders. Herein we report the case of a 12-year-old boy with Niemann-Pick disease who developed generalized lichen nitidus.

Líquen nítido generalizado é uma dermatose inflamatória crônica, rara, com achados histológicos muito característicos. Sua patogênese não está completamente esclarecida e, muito raramente, tem sido associado a doenças genéticas. Reportamos o caso de um doente do sexo masculino, de 12 anos de idade, com Doença de Niemann-Pick, que desenvolveu líquen nítido generalizado.