Rehabilitative treatment in peripheral artery disease: protocol application and follow-up.

AIM: Peripheral arterial disease (PAD) is a chronic figure suitable to be treated at the II stage to prevent the extreme developments both of the critical limb ischemia and the amputation, as well. The aim of this study was to establish a rehabilitation program (pharmacological and physical) focused not only on the improvement of the flow but also on the metabolic rebalancing in the claudicant limb. METHODS: The study enrolled 222 patients, (125 non-diabetics and 97 diabetics): 54 II A and 168 II B stage; 172 patients (131 II B and 41 II A; 104 non-diabetics and 68 diabetics) were submitted to iv. L-propionil carnytine (Lpc) and physical training on treadmill or exercise bike and 50 patients to iv. therapy alone. Instrumental (Rheoscreen, Oximetry, ABI, walking distance measurement) and clinical checks (questionnaire - Appendix 1) were performed at days: T0, T45,T 90,T180, T230 and during the follow up stated at T 90,T180,T360 from T 230 (end of DH). RESULTS: A significant increasing of the walking distance has been reached in the group undergoing the rehabilitation program. Treadmill: non-diabetics +261.48% at 0% and +122.53% at slope 10% (T230) further increasing to +502.31% at 0% and +289.42% at slope 10% (T360); diabetics: + 158.49% at T0 and + 98.26% at slope 10% (T230) further increased to +287.74% at 0% and +197.39% at 10% (T360) in comparison with the group which had only iv. Lpc : non-diabetics +141.63% at 0% and +104.08% at slope 10% (T230) further increased to +202.064% at 0% and +155.10% at slope 10% (T360); diabetics: +109.124% at T0 and +100% at slop 10% (T230) further increased to +171.08% at 0% and +140% at 10% (T360) . Exercise bike: non-diabetics: +170.27% at T230 in comparison T0 increased to +305.4% at T360; diabetics: +166.66 at T230 reaching +288.88% at T 360. CONCLUSION: Our rehabilitative program gives not only good results at the end of the treatment but mainly stable, with the chance to reach further improving of both walking distance and quality of life, particularly in those patients which observe constantly the physical training.

Plasma levels of adrenomedullin, a vasoactive peptide, in type 2 diabetic patients with and without retinopathy.

AIM: The aim of this study was to investigate whether adrenomedullin (AM) secretion is modified in type 2 diabetic patients with and without retinopathy. METHODS: The study was performed on 92 patients with type 2 diabetes, 65 of whom had uncomplicated diabetes, 27 had retinopathy, and 40 had mild to moderate hypertension. Patients with serum creatinine levels >1.2 mg/dL, were excluded. Circulating AM was assayed using a specific radioimmunoassay. RESULTS: AM concentrations were significantly higher in type 2 diabetic patients (25+/-2.1 pg/mL) than in the 31 normal subjects (11+/-0.8 pg/mL) (P<0.001). Type 2 diabetic patients with retinopathy had significantly greater AM levels (30.8+/-3.4 pg/mL) than both controls (P<0.001) and type 2 diabetic patients without retinopathy (25.2+/-2 pg/mL same as previous value) (P<0.001). No statistical difference was found between diabetic patients with pre-proliferative retinopathy (27.3+/-4.7 pg/mL) and proliferative retinopathy (24+/-3.1 pg/mL) (P=0.543). In type 2 diabetic patients, a significant correlation between plasma AM levels and HbA1c values (r=0.467; P<0.01) was found. CONCLUSION: Our findings indicate that circulating AM is increased in type 2 diabetic patients and that increase correlates with poor glucose metabolic control and presence of retinopathy.

[Transverse study of personality characteristics in patients with arterial hypertension]. / Studio trasversale sui caratteri di personalità in pazienti ipertesi.

OBJECTIVE: To verify whether hypertensive patients, with recent or old poor-controlled hypertension, asymptomatic for anxiety and/or depression, seem more disturbed in personality than normotensive patients. MATERIALS AND METHODS: 122 patients with arterial hypertension (62 women, 60 men, mean age 47 +/- 12.7 years, divided in new-hypertensive patients who don't take any drugs and old-hypertensive patients with a chronic therapy) and 65 normotensive subjects (37 women, 28 men, middle age 41 +/- 11.7 years) answered two self-extiming questionnaires: A.S.Q. by Krug and Cattel and C.D.Q. by Krug and Laughlin. For every group of variables it has been calculated the mean and standard deviation and statistical analysis was performed by Mann-Whitney's t test. A value of p < 0.05 was considered statistically significatant. RESULTS: 37 hypertensive patients (30.3%) were positive in the C.D.Q. and 34 (27.8%) in the A.S.Q. test. In the group of normotensive subjects, 13 (20%) were positive in C.D.Q. and 12 (8.4%) in A.S.Q. There was a statistic difference in C.D.Q and A.S.Q. between hypertensive and normotensive subjects. No statistic difference was found in C.D.Q. and A.S.Q. between new and old-hypertensives. CONCLUSIONS: The study has shown a significant higher level of anxiety and depression in hypertensive subjects as compared to normotensives. However, no significant difference in anxiety and depression levels was found between new- and old-hypertensive patients or in relation with the use of antihypertensive drugs.

Ambulatory monitoring of blood pressure (AMBP) in patients with primary hyperparathyroidism.

The purpose of our study was to evaluate the behaviour of blood pressure (BP) by ambulatory monitoring of blood pressure (AMBP) in 53 patients with primary hyperparathyroidism (PHPT) compared to 100 essential hypertensive (EH) and 31 healthy subjects (HS). The correlations between calcium-phosphorus metabolism and haemodynamic parameters in all groups are included in the study. AMBP was performed using the oscillometric technique (Space-Labs, 90207, Redmond, WA, USA) and the following AMBP parameters were evaluated: average day time systolic (S) and diastolic (D) blood pressure (BP) and heart rate (HR) (when awake), average night time SBP, DBP and HR (when asleep) and average 24-h-SBP, DBP and HR. The definition of 'dipper' or 'non-dipper' subjects was established if night time SBP and DBP fall was >10% and <10%, respectively. In total, 25 PHPT patients (47.2%) were hypertensive (HT-PHPT) and 28 PHPT (52.8%) were normotensive (NT-PHPT). Mean 24-h-SBP and DBP obtained by AMBP was higher in HT-PHPT (P < 0.05) and EH (P < 0.05) than in NT-PHPT and HS. The multiple linear regression has shown that in PHPT-HT patients ionized calcium is an independent factor for the rise of 24-h-DBP values (r: 0.497; P < 0.05) and daytime DBP values (r: 0.497; P < 0.05). In 56% of HT-PHPT patients there is an absence of physiological BP nocturnal fall ('non-dipper'), which is statistically significant (P < 0.05) compared with 'non-dipper' EH patients (30%). In conclusion, in our study the prevalence of hypertension in PHPT was 47%. AMBP revealed that the 'non-dipping 'pattern was much higher in HT-PHPT patients in respect to EH patients.

Acute hyperinsulinemia is associated with increased plasma adrenomedullin concentrations in uncomplicated obesity.

OBJECTIVE: Adrenomedullin (AM) is a potent hypotensive peptide which may be implicated in the insulin regulatory system. Acute hyperinsulinemia exerts no influence on plasma AM in normal subjects while no data on obese subjects has been reported. PURPOSE: The aim of the study was to investigate the effect of acute hyperinsulinemia on the plasma AM concentration in patients with uncomplicated obesity. RESEARCH METHODS: We measured the plasma AM levels in 23 obese subjects (BMI 41.9 +/- 9.8 kg/m2), 21 females and 2 males (mean age 31 +/- 7.2 years), before and during a euglycemic hyperinsulinemic clamp. The control group consisted of 43 healthy subjects (HS) (22 males and 21 females; mean age 38 +/- 12 years; BMI 23.3 +/- 3.2 kg/m2). RESULTS: Baseline plasma AM was found to be higher in obese subjects (20.4 +/- 8.4 pg/ml) than in normal subjects (11.3 +/- 0.8 pg/ml) (p < 0.001). A significant increase in the plasma AM levels was observed in obese subjects during acute hyperinsulinemia (from 20.4 +/- 8.4 pg/ml at 0 min to 26 +/- 8.9 pg/ml at 120 min, p < 0.02). Plasma AM concentrations were significantly correlated with insulin levels at 30 min (r = 0.44; p = 0.04) and 120 min (r = 0.40, p = 0.05) during the clamp. DISCUSSION: In conclusion, acute hyperinsulinemia induced a significant increase in the plasma levels of AM in uncomplicated obese subjects. Hyperinsulinemia may, at least in part, regulate levels of AM in obesity, explaining the high levels of the peptide in these subjects.

Adrenomedullin, a new peptide, in patients with insulinoma.

BACKGROUND: It has been demonstrated that adrenomedullin, a newly discovered peptide, affects the release of insulin from pancreatic islets cells, suggesting a role in the insulin-regulating system. OBJECTIVE: To investigate whether adrenomedullin secretion is modified in patients with insulin-secreting islet cell tumours. DESIGN: The study was performed in nine patients with surgically treated insulinoma. Circulating adrenomedullin was assayed using a specific radioimmunoassay and its localization and distribution in the tumour were determined by means of immunohistochemistry. RESULTS: Adrenomedullin concentrations were significantly greater in patients with insulinoma (6.6 +/- 3.2 fmol/ml) than in controls (2.1 +/- 1.1 fmol/ml). In six patients monitored before and after surgery, plasma adrenomedullin decreased from 6.3 +/- 2.9 fmol/ml to 3.0 +/- 1.6 fmol/ml. Immunoreactive adrenomedullin was localized exclusively in the tumours cells, whereas stroma, surrounding pancreas parenchyma and major ducts were negative for the peptide. CONCLUSIONS: Our findings indicate that circulating adrenomedullin is increased in insulinoma and that this increase is related to the neoplastic phenotype.

Adrenomedullin concentrations are elevated in plasma of patients with primary hyperparathyroidism.

The aim of the study was to evaluate plasma adrenomedullin (AM) concentration in primary hyperparathyroidism (PHP) and its effect on the regulation of blood pressure. Forty-one patients with PHP (25 normotensive and 16 hypertensive), and 31 healthy subjects (HS) were included in the study. As expected the total and ionized calcium and i-PTH serum levels were significantly higher in patients with PHP than in HS (P <.001). No significant difference was found in calcium-phosphorus metabolism parameters between normotensive and hypertensive PHP patients. Serum i-PTH levels correlated positively with systolic blood pressure (SBP) (r = 0.510; P <.02), diastolic blood pressure (DBP) (r = 0.586; P <.01) and heart rate (HR) (r = 0.486; P <.043) only in hypertensive PHP patients. Overall, mean plasma AM concentrations were significantly higher in PHP patients (16.1 +/- 7.9 pg/mL) than in HS (11.3 +/- 4.8 pg/mL) (P <.003) and correlated with i-PTH (r = 0.430; P <.005). However, in hypertensive PHP patients plasma AM levels (22.5 +/- 4.7 pg/mL) were higher than in normotensive PHP patients (11.6 +/- 1.8 pg/mL) (P <.001) and correlated with DBP (r = 0.902, P <.0029). In HS no correlation was found between plasma AM values and biohumoral, hormonal, or hemodynamic parameters. In conclusion, we demonstrated that in patients with PHP, plasma AM concentrations are increased and correlate with i-PTH and blood pressure values. We suggest that increased AM levels could be a compensatory factor in the defence mechanism against further blood pressure elevation.

Plasma levels of endothelin-1 increase in patients with sarcoidosis and fall after disease remission.

BACKGROUND: Sarcoidosis is a chronic systemic disease, characterized by an imbalance of immunity processes and the presence of granuloma. Endothelin-1, a new vasoactive and bronchoconstrictive peptide, is a powerful mitogen for smooth muscle cells and fibroblasts and plays a role in the inflammation state. We postulate that endothelin-1 has a role in sarcoidosis. METHODS: We studied the behaviour of circulating levels of endothelin-1 in 20 patients with sarcoidosis and its correlation with some biochemical parameters of activity disease, such as erythrocyte sedimentation rate (ESR) and serum angiotensin-converting enzyme (SACE). We measured serum levels of ESR, SACE, calcium and plasma endothelin-1 levels in all patients at the beginning of the study and one again in 9 patients with clinical-biochemical remission of disease after steroid treatment. RESULTS: In patients with sarcoidosis, circulating levels of endothelin-1, SACE and ESR were significantly higher (p<0.001) than those of healthy subjects. Moreover, in patients with pulmonary involvement, there was a significant statistical difference (p<0.001) between endothelin-1 levels and radiological stage compared to normal subjects. In the 9 patients with remission of disease, both endothelin-1 levels and parameters of activity disease normalized. CONCLUSIONS: Our results seem to suggest that the increase of plasma endothelin-1 levels in active sarcoidosis can represent an expression of the endothelial dysfunction and reflect the picture of cellular activation.

[Incidentalomas of the adrenal glands. Personal cases and review of the literature]. / Incidentalomi del surrene. Casistica personale e revisione della letteratura.

BACKGROUND: The growing use of sensitive non-invasive methods to image the abdomen such as ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI), have resulted in increasing recognition of adrenal incidentalomas. METHODS: In this study, we report the clinical, endocrine and radiologic evaluation of 75 patients (50 women and 25 men, mean age 56 +/- 14 years) with adrenal incidentaloma (size 1 to 18 cm, mean 3 +/- 2.5 cm). None of the patients showed any symptoms or clinical signs that might indicate the existence of adrenal dysfunction. The patients underwent basal and dynamic evaluation of the hypothalamic-pituitary-adrenal axis, renin-angiotensin-aldosterone system, and adrenomedullary function. Moreover, CT and MRI scan and Iodo-cholesterol (NP-59) scintigraphy were performed. RESULTS: The endocrine evaluation indicated 11 cases of pre-clinical Cushing's syndrome, 2 cases of pheochromocytoma and 62 not-functionally adrenal masses. On the basis of endocrine and morphologic data, 29 patients underwent surgical treatment: 20 adrenocortical adenoma, 2 pheochromocytomas, 2 not-cortisol-secreting adrenal carcinomas, 1 adrenal lymphoma, 1 adrenal metastasis, 1 myelolipoma, 1 hemorrhage and 1 pseudocystis. CONCLUSIONS: In conclusion, patient with an incidentally discovered mass has to be investigated to detect malignancy and subtle hormonal overproduction, to select the cases for surgical treatment.

Plasma adrenomedullin concentrations in patients with renovascular or malignant hypertension.

AIM: The aim of the present study was to investigate the behaviour of plasma adrenomedullin (AM), a hypotensive peptide, in patients with malignant (MHT) and renovascular hypertension (RVH), 2 pathologic conditions in which renin-angiotensin system (RAS) is activated and to compare them with those in essential hypertensive patients (EHT) and normotensive subjects (NS). METHODS: Three groups of hypertensive patients have been studied: group 1 (4 patients with MHT), group 2 (10 patients with RVH), group 3 (24 patients with EHT) and 21 patients NS were enrolled as controls. In all patients, 10 ml vein blood samples were collected and AM was measured with specific radioimmunoassay. RESULTS: As expected, the plasma renin activity (PRA) levels in the RVH and MHT patients were significantly higher (p<0.0001) respect to NS and EHT. The mean plasma AM (+/-SD) concentrations in EHT (22.5+/-9.1 pg/ml) and RVH (46.8+/-19.4 pg/ml) were significantly (p<0.0001) higher than those in NS (13.7+/-6.1 pg/ml). The plasma AM concentrations were further elevated in MHT patients (107+/-12.3 pg/ml) and were significantly higher (p<0.0001) than those in EHT and RVH patients. In the MHT patients the elevated plasma AM levels, similarly to blood pressure and PRA values, declined after antihypertensive treatment (36.8+/-5.7 pg/ml; p<0.01). CONCLUSION: In conclusion, the findings demonstrated that the plasma AM concentrations were increased in proportion to the severity of arterial hypertension. RAS was activated in patients with MHT and RVH suggesting that activation of this system may contribute to increased in the plasma levels of AM.

Endothelin-1 circulating levels increase in patients with orthotopic heart transplantation and in chronic therapy with cyclosporine.

BACKGROUND: The aim of the study was to investigate the behaviour of plasma levels of endothelin-1 (ET-1), an endothelial peptide with vasoconstrictive and proliferative actions, in patients with cardiac transplantation and in chronic treatment with cyclosporine A, some of whom became hypertensive after cardiac transplantation. METHODS: We studied: 1) 18 consecutive patients (15 M, 3F; mean age 53 +/- 7 yrs) who underwent cardiac transplantation about six months ago at least (range 6-108 months); 2) 15 patients with essential arterial hypertension (10 M, 5 F; mean age 42 +/- 15 yrs) without organ damage; 3) 21 normal subjects (15 M, 6 F; mean age 31 +/- 12 yrs). Plasma levels of ET-1 (RIA), haemodynamic and functional renal parameters were determined in all groups and plasma levels of cyclosporine were measured in patients with cardiac transplantation. RESULTS: ET-1 was higher in patients with cardiac transplantation than in the other two groups (p < 0.05); instead there was no difference between patients with essential arterial hypertension and controls (p>0.05). A statistical difference was found between circulating ET-1 in hypertensive transplanted patients. In heart transplanted patients a positive and significative correlation was found between plasma levels of ET-1 and systolic (r=0.525; p<0.037) blood pressure.

[High circulating levels of adrenomedullin and endothelin-1 in obesity associated with arterial hypertension]. / Elevati livelli circolanti di adrenomedullina e di endotelina-1 nell'obesità associata ad ipertensione arteriosa.

BACKGROUND: The aim of the study was to investigate the behavior of two endothelial vasoactive peptides, adrenomedullin (vasodilator) and endothelin-1 (vasoconstrictor), in human obesity with and without arterial hypertension. METHODS: The study was carried out on 30 obese subjects (body mass index > 27 kg/m2) divided into two groups: 15 normotensive obese patients (10 males, 5 females, mean age 42 +/- 12 years) and 15 hypertensive obese patients (9 males, 6 females, mean age 42 +/- 13 years). The control group consisted of 21 normal subjects (12 males, 9 females, mean age 38 +/- 12 years) and of 16 patients with essential hypertension (10 males, 6 females, mean age 41 +/- 12 years) but without organ damage. All studied subjects were taking a normocaloric (20-22 kcal/kg/day), normosodic (120-140 mEq/day) and normopotassic (50-60 mEq/day) diet. Between 8.00 and 9.00 a.m., a venous blood sample was taken for the determination (radioimmunoassay) of plasma adrenomedullin and endothelin-1 concentrations. RESULTS: Plasma adrenomedullin levels in normal subjects (13.7 +/- 6.1 pg/ml) were similar to those in normotensive obese patients (14.8 +/- 7.2 pg/ml), whereas in hypertensive obese patients (22.5 +/- 9.1 pg/ml) and in those with essential hypertension (22.7 +/- 8.2 pg/ml) levels were significantly higher (ANOVA = 0.000, p < 0.05) than those of normal subjects and of normotensive obese patients. Moreover, endothelin-1 plasma concentrations were found to be significantly higher (ANOVA = 0.000, p < 0.05) in hypertensive obese patients (10.3 +/- 2.7 pg/ml) compared to normal subjects (6.5 +/- 2.4 pg/ml), normotensive obese patients (8.3 +/- 1.5 pg/ml) and to those with essential hypertension (8.5 +/- 2.9 pg/ml). In patients with essential hypertension, a positive correlation (r = 0.493, p < 0.05) was found between adrenomedullin and endothelin-1 plasma levels. CONCLUSIONS: These results revealed that in human obesity associated with arterial hypertension there is an increased production of plasma adrenomedullin and endothelin-1 that, with their opposite vasoactive properties (vasodilation/vasoconstriction), can contribute to this pathological association.

Severity of human hypertension in relation to the age in which high blood pressure makes its presumptive appearance.

PURPOSE: The present study investigates the properties of blood pressure (BP) circadian rhythm (CR) in newly-diagnosed hypertensives (NDH) as a function of the chronological age in which hypertension became manifest. MATERIALS AND METHODS: The study was performed on 141 NDH (71 males and 70 females, ranging in age from 24 year to 79 years), who were monitored in their 24-h BP via a non-invasive, ambulatory, automated recorder. The relation between the properties of BP CR and the age of the development of hypertension was investigated via the Clinospectror method, a trend analysis (periodic-linear regression method) for rhythmic biophenomena. RESULTS: A trend was detected for each one of the three properties of BP CR in relation with the age in which high BP made its appearance. As a matter of fact, the daily mean level (mesor) of BP CR was seen to be progressively less pronounced. The amplitude was found to show a progressive increment of its extent. The acrophase was seen to show a progressive antemeridian rotation of its timing. CONCLUSIONS: These trends suggest that hypertension tends to be less severe when its development occurs in subjects older in age. Such a less pronounced severity is, however, accompanied by a more pronounced oscillation of BP values during the 24-h of the day. Such a higher circadian variability, in turn, tends to show its highest expression during the morning hours of the day.

False-positive diagnosis of adrenal pheochromocytoma on iodine-123-MIBG scan.

1-123 metaiodobenzylguanidine (1-123 MIBG) scintigraphy is known for its high specificity in detecting pheochromocytoma and other tumors of neural crest origin. In this rare case report, we describe a definite adrenocortical adenoma that demonstrated false-positive uptake at I-123 MIBG scintigraphy and a remarkable accumulation of 75-SE-6-beta-selenomethyl-norcholesterol.

A case of pheochromocytoma with renal artery stenosis and post-surgical watery diarrhea.

A 35-year-old woman was admitted to our hospital with the following complaints, headache, sweating, anxiety, dizziness, nausea, vomiting and severe hypertension. The technical images (abdominal CT, scintigraphic octreotide scan and renal arteriography) revealed the presence of a left adrenal pheochromocytoma and stenosis of the renal artery. Ten days following adrenalectomy, watery diarrhea appeared. The long-acting somatostatin analogue octreotide (LAR, 30 mg/month, i.m.), was started, and after 2 weeks diarrhea decreased and gradually disappeared. In conclusion, we were confronted with an unusual case of pheochromocytoma associated with renal artery stenosis and the appearance of watery diarrhea some days after surgical treatment. Treatment with octreotide brought about the remission of diarrhea in this patient.

Plasma adrenomedullin concentrations in patients with adrenal pheochromocytoma.

BACKGROUND: The hypotensive peptide adrenomedullin was first isolated in extracts of human pheochromocytoma. There is, however, no information available on the behaviour of circulating adrenomedullin or on the correlation with catecholamines in patients with pheochromocytoma. OBJECTIVES: 1) to investigate whether plasma adrenomedullin levels were changed in 10 patients with pheochromocytoma when compared to 21 healthy subjects and 16 patients with essential hypertension; 2) to determine whether or not adrenomedullin has a counter-regulatory role in catecholamine excess in pheochromocytoma or is responsible for hemodynamic modifications before and after tumour resection; 3) to determine tissue distribution of iradrenomedullin in the pheochromocytoma. METHODS: Plasma adrenomedullin and catecholamine levels were measured in all patients with pheochromocytoma before and four weeks after tumour removal. In the four patients undergoing resection of tumours, plasma levels of adrenomedullin were measured at different time-points during surgery. RESULTS: The mean plasma adrenomedullin concentrations ( SD) in patients with pheochromocytoma (37.9 +/- 6pg/ml) were significantly higher (p<0.0001) than those in normal subjects (13.7 +/- 6.1 pg/mI) and patients with essential hypertension (22.5 +/- 9.lpg/ml). Adrenomedullin levels correlated with plasma noradrenaline (r = 0.516, p = 0.0124). In all patients with pheochromocytoma, plasma adrenomedullin concentrations decreased after removal of tumours (from 37.9 +/- 6 to 10.9 +/- 4.6 pg/ml; p < 0.0001). In the four patients studied during surgery, baseline plasma adrenomedullin and noradrenaline levels were markedly elevated, and increased significantly with tumour manipulation, decreasing 24 hours after operation. Adrenal medulla cells surrounding the pheochromocytoma site stained for ir-adrenomedullin, whereas only isolated cells of pheochromocytoma stained for the peptide. CONCLUSIONS: This study demonstrates that circulating adrenomedullin is increased in pheochromocytoma, and is also correlated with plasma noradrenaline levels. Adrenomedullin may represent an additional biochemical parameter for clinical monitoring of patients with pheochromocytoma.

Type II benign osteopetrosis (Albers-Schönberg disease) caused by a novel mutation in CLCN7 presenting with unusual clinical manifestations.

A 16-year-old male patient with type II autosomal dominant benign osteopetrosis (ADO) was genotyped and found to harbor a novel mutation in exon 25 of the gene encoding for the osteoclast-specific chloride channel, CLCN7, inherited from the father, who was asymptomatic. The patient had normal biochemical findings and acid-base balance, except for increased serum levels of creatine kinase, lactic dehydrogenase, and the bone formation markers bone alkaline phosphatase isoenzyme, osteocalcin and N-terminal type I collagen telopeptide/creatinine ratio. Unusual generalized osteosclerosis was observed together with a canonical increase in vertebral and pelvis bone mass. An affected first grade cousin presented with normal biochemical findings and a milder osteosclerotic pattern of the pelvis. At the cellular level, cultured osteoclasts from the patient showed increased motility, with lamellipodia, membrane ruffling and motile pattern of podosome distribution, all of which could have contributed to functional impairment of bone resorption. The present report documents a novel mutation of the CLCN7 gene causing osteopetrosis in a radiologically uncertain form of the diseases, with apparent incomplete penetrance.