Endocrinological and metabolic profile of Gaucher disease patients treated with enzyme replacement therapy.

OBJECTIVES: Gaucher disease (GD) is a lysosomal storage disease caused by glucocerebrosidase (GCase) enzyme deficiency. Gaucher cells transformed from the macrophages by progressive sphingolipid accumulation and infiltrate bone marrow, spleen, liver, and other organs. The accumulation of substrate causes inflammation, compromised cellular homeostasis, and disturbed autophagy. It has been hypothesized that this proinflammatory state of GD leads cytokines and chemokines release. As a result of inflammatory process, the cellular dysfunction caused by disruption of cellular signaling, organelle dysfunction, or autoimmune antibodies may affect endocrine profile of GD patients such as hormone levels, lipid profile, and bone mineral density status. METHODS: A total of 13 patients confirmed to have GD, 12 non-neuronopathic type and one subacute neuronopathic type, were enrolled in our study. RESULTS: The median treatment duration in the enzyme therapy was 13.33 years (9-26 years). At least one endocrinological abnormality was detected in blood tests of nine patients. Hyperinsulinism was the most common finding although fasting blood glucose levels HgbA1c levels were normal in all patients. Two patients had osteopenia, and osteoporosis was detected in two patients. Low HDL levels were detected in six patients, but HDL levels below 23 mg/dL associated with disease severity have been detected in two patients who have not receiving enzyme replacement therapy. None of patients had thyroidal dysfunction. CONCLUSIONS: This study had revealed endocrinological abnormalities in GD patients that have not led any severe morbidity in our patients. However, thyroid hormone abnormalities, insulin resistance, or lipid profile abnormalities may cause unpredictable comorbidities. Endocrinological assessment in GD patients in routine follow-up may prevent possible clinical manifestation in long term as well as can define efficacy of ERT on endocrine abnormalities.

Mucopolysaccharidosis type IIID: 12 new patients and 15 novel mutations.

Mucopolysaccharidosis III D (Sanfilippo disease type D, MPS IIID) is a rare autosomal recessive lysosomal storage disorder previously described in only 20 patients. MPS IIID is caused by a deficiency of N-acetylglucosamine-6-sulphate sulphatase (GNS), one of the enzymes required for the degradation of heparan sulphate. So far only seven mutations in the GNS gene have been reported. The clinical phenotype of 12 new MPS IIID patients from 10 families was studied. Mutation analysis of GNS was performed in 16 patients (14 index cases). Clinical signs and symptoms of the MPS IIID patients appeared to be similar to previously described patients with MPS III. Early development was normal with onset of behavioral problems around the age of 4 years, followed by developmental stagnation, deterioration of verbal communication and subsequent deterioration of motor functions. Sequence analysis of the coding regions of the gene encoding GNS (GNS) resulted in the identification of 15 novel mutations: 3 missense mutations, 1 nonsense mutation, 4 splice site mutations, 3 frame shift mutations, 3 large deletions and 1 in-frame small deletion. They include the first missense mutations and a relatively high proportion of large rearrangements, which warrants the inclusion of quantitative techniques in routine mutation screening of the GNS gene.

Endothelial activation and inflammation in prepubertal obese Turkish children.

To investigate the degree of endothelial activation and inflammation in prepubertal obese children and to determine the relationship between the markers of endothelial activation, inflammation, and cardiovascular risk factors. In 30 obese and 28 healthy prepubertal children, soluble intercellular adhesion molecule-1 and endothelial leukocyte adhesion molecule-1 (sE-selectin) as markers of endothelial activation and soluble vascular cell adhesion molecule-1 (sVCAM-1) and C-reactive protein (CRP) as markers of endothelial inflammation in addition to cardiovascular risk factors including blood lipids, glucose, insulin, hemoglobin A1c, and systolic and diastolic blood pressure were investigated and compared. The tests were repeated after an oral glucose tolerance test in the obese group. Fasting CRP levels were found to be significantly higher in obese children. Vascular cell adhesion molecule-1 levels were found to be significantly increased in obese children after oral glucose tolerance test. Fasting CRP was positively correlated with body mass index (BMI) and low-density lipoprotein, whereas sE-selectin was positively correlated with total cholesterol. In the obese group, postload levels of soluble sE-selectin was positively correlated with low-density lipoprotein; sVCAM-1 was positively correlated with insulin and homeostasis model assessment values. Postload soluble intercellular adhesion molecule-1, sVCAM-1, and soluble sE-selectin levels were also positively correlated with each other. In the fasting state, BMI was the significant independent risk factor for CRP, and total cholesterol was the significant risk factor for soluble sE-selectin. Insulin resistance was the significant independent risk factor for postload sVCAM-1, and postload low-density lipoprotein stood as the significant independent risk factor for postload soluble sE-selectin. Endothelial inflammation is present in obese prepubertal children and is mainly associated with insulin resistance and lipid levels as well as BMI.