Long-term follow-up of indolent mastocytosis in adults.

OBJECTIVE: To evaluate the natural course of indolent mastocytosis in adults. DESIGN: A retrospective long-term follow-up study. SETTING: The Department of Endocrinology of a University Hospital. PATIENTS: Sixteen adult patients with a diagnosis of indolent mastocytosis and sufficient biochemical data for statistical analysis. One patient had paediatric-onset cutaneous mastocytosis, whilst the others had adult-onset systemic mastocytosis. Ages at the end of follow-up ranged from 23 to 79, median 50 years. Follow-up periods per patient lasted from 13 to 135 months, median 90 months. MEASUREMENTS: Urinary excretions of the histamine metabolites N tau-methylhistamine (MH) and N tau-methylimidazoleacetic acid (MIMA), and signs and symptoms of the disease. RESULTS: The excretion of MH but not MIMA increased in four patients (ages 37, 45, 61 and 65 years) and decreased in two patients (ages 26 and 48 years), including the only patient with paediatric-onset cutaneous mastocytosis. The excretion of MIMA but not MH increased in none and decreased in one patients (age 51 years). The excretions of both MH and MIMA increased in one patient (age 23 years) and decreased in two patients (ages 65 and 79 years). The excretion of MH and MIMA can be considered to have been stable in one patient (age 49 years). In the five remaining patients, observation periods were rather short. A definite judgement on the course of their disease could not be given. In the two patients in whom the excretion of both MH and MIMA decreased, the enlarged spleen decreased in size, whilst in the other patients, signs and symptoms did not change. There were no accompanying myeloproliferative disorders in any patient. No special treatment aiming at a reduction in mast cell load has been given. Rates of change over the whole follow-up period ranged from -8.4 to +25.1% per year. CONCLUSION: The natural course of indolent adult-onset mastocytosis is not always progressive. Our data show that the activity of adult-onset indolent mastocytosis, as measured by urinary excretion of MH and MIMA and clinical signs and symptoms, can substantially decline, especially in older patients.

Lysinuric protein intolerance characterized by bone marrow abnormalities and severe clinical course.

STUDY OBJECTIVE: To evaluate phenotypic variability of lysinuric protein intolerance in a cohort of nine Italian patients. DESIGN: Retrospective analysis of patient records. SUBJECTS: Nine Italian patients (seven independent families), all originating from southern Italy, observed during the last 14 years. RESULTS: Some of the patients had unique clinical features, including bone marrow abnormalities featuring erythroblastophagocytosis (five patients) and clinical course and the outcome of the disease, have also been observed: respiratory involvement was present in five cases, with a lethal picture of "alveolar proteinosis" in one. Severe kidney involvement, with both glomerular and tubular damage and rapidly progressing to chronic renal failure, has been observed in one case. CONCLUSION: Lysinuric protein intolerance may cause severe multisystem involvement, which requires early and careful monitoring. Some peculiar clinical findings observed in Italian patients point to a genetic heterogeneity of lysinuric protein intolerance.

Elevated urinary dolichol excretion in the Hermansky-Pudlak syndrome. Indicator of lysosomal dysfunction.

The Hermansky-Pudlak syndrome, a triad of albinism, platelets lacking dense bodies, and storage of ceroid-like material in tissues, occurs approximately once in 2,000 northwestern Puerto Ricans. The manifestations of storage disease are variable and include granulomatous colitis, restrictive lung disease, kidney failure, and cardiomyopathy. The autofluorescent material stored in the Hermansky-Pudlak syndrome is histochemically similar to that stored in neuronal ceroid/lipofuscinosis. The material in neuronal ceroid/lipofuscinosis contains dolichols, which are components of lysosomes, and patients show increased urinary excretion of dolichols. This study of 49 patients with the Hermansky-Pudlak syndrome found that urinary dolichol levels are increased in those patients with evidence of ceroid storage in the kidneys but are not elevated when storage occurs in tissues other than the kidneys. The excretion of ceroid was not influenced by the saturation state of dietary fat. A defect in processing of membranes of lysosomes, melanosomes, and dense bodies may be involved in the syndrome.