Three Siblings With Woodhouse-Sakati Syndrome: A Case Report of A New Saudi Family.

Woodhouse-Sakati syndrome (WSS) is a rare autosomal recessive multi-system genetic disease caused by loss of function mutations in the DCAF17 gene on chromosome 2q31.1. The disease is characterized by gradual neurologic degeneration and polyendocrinopathy, particularly noteworthy for hypogonadism, beginning in early adolescence. Clinical features show wide variability with no clear genotype-phenotype correlation. The pathophysiology of WSS is unclear at present and no specific treatment is available other than hormone replacement which is administered in the course of individualized symptomatic multidisciplinary care. Genetic testing helps in confirming the diagnosis along with genetic counseling of the patient and family members. Here we report multiple cases of WSS in three siblings from a new Saudi Arabia family who were diagnosed with WSS as a consequence of a common founder mutation in the DCAF17 gene with DNA analysis showing a homozygous single nucleotide frameshift deletion (c.436delC) in exon 4 of the gene.

Bone mineral density in patients with longstanding type 1 diabetes: Results from the Canadian Study of Longevity in Type 1 Diabetes.

AIM: It is currently unclear if longstanding type 1 diabetes (T1D) affects bone mineral density (BMD). METHODS: BMD measured by dual-energy X-ray absorptiometry and history of fragility fracture was determined in 75 T1D participants with ≥50 years of diabetes duration and 75 age- and sex-matched non-diabetic controls. BMD T-scores were determined for the lumbar spine (LS), total hip (TH) and femoral neck (FN). RESULTS: T1D participants had median diabetes duration of 54 [52, 58] years, 41 (55%) were females, and mean A1c was 7.3 ±â€¯0.8%. T1D females had higher LS T-scores compared to female controls (-0.3 ±â€¯1.2 vs. -1.1 ±â€¯1.4, p = 0.014), lower FN T-scores (-1.5 ±â€¯1.0 vs. -1.2 ±â€¯0.9, p = 0.042) and more fragility fractures (7 (17%) vs. 1 (2%), p = 0.021). In T1D, higher A1c was associated with higher adjusted odds of fragility fracture (p = 0.006). T1D males and controls showed no difference in BMD or fractures. CONCLUSIONS: There were no substantial differences in T-score between T1D and matched controls; however, T1D females showed higher BMD at the LS and possibly paradoxically higher fragility fractures compared to matched controls. These findings suggest that lower T-scores may not be associated with a history of fragility fracture in females with longstanding T1D and that other factors should be investigated.

Adiposity Impacts Intrarenal Hemodynamic Function in Adults With Long-standing Type 1 Diabetes With and Without Diabetic Nephropathy: Results From the Canadian Study of Longevity in Type 1 Diabetes.

OBJECTIVE: Central adiposity is considered to be an important cardiorenal risk factor in the general population and in type 1 diabetes. We sought to determine the relationship between central adiposity and intrarenal hemodynamic function in adults with long-standing type 1 diabetes with and without diabetic nephropathy (DN). RESEARCH DESIGN AND METHODS: Patients with type 1 diabetes (n = 66, duration ≥50 years) and age-/sex-matched control subjects (n = 73) were studied. The cohort was stratified into 44 DN Resistors (estimated glomerular filtration rate [eGFR] >60 mL/min/1.73 m2 and <30 mg/day urine albumin) and 22 patients with DN (eGFR ≤60 mL/min/1.73 m2 or ≥30 mg/day urine albumin). Intrarenal hemodynamic function (glomerular filtration rate for inulin [GFRINULIN], effective renal plasma flow for p-aminohippuric acid [ERPFPAH]) was measured. Afferent arteriolar resistance, efferent arteriolar resistance, renal blood flow, renal vascular resistance [RVR], filtration fraction, and glomerular pressure were derived from the Gomez equations. Fat and lean mass were quantified by DXA. RESULTS: Whereas measures of adiposity did not associate with GFRINULIN or ERPFPAH in healthy control subjects, trunk fat mass inversely correlated with GFRINULIN (r = -0.46, P < 0.0001) and ERPFPAH (r = -0.31, P = 0.01) and positively correlated with RVR (r = 0.53, P = 0.0003) in type 1 diabetes. In analyses stratified by DN status, greater central adiposity related to lower GFRINULIN values in DN and DN Resistors, but the relationships between central adiposity and ERPFPAH and RVR were attenuated and/or reversed in patients with DN compared with DN Resistors. CONCLUSIONS: The adiposity-intrarenal hemodynamic function relationship may be modified by the presence of type 1 diabetes and DN, requiring further study of the mechanisms by which adiposity influences renal hemodynamic function.

Carbonic Anhydrase II Deficiency in a Saudi Woman.

OBJECTIVE: Carbonic anhydrase (CA) II deficiency is a rare autosomal recessive disorder caused by mutation in the CA II gene that leads to osteopetrosis, renal tubular acidosis (RTA), and cerebral calcification. Our aim is to present a patient with the classic triad of CA II deficiency syndrome to enhance the awareness about this rare syndrome. METHODS: We describe the clinical and radiological findings of a Saudi woman patient with CA II deficiency syndrome. RESULTS: A Saudi woman in her 20s presented to our hospital for evaluation of increased bone density. She was known to have delayed developmental milestone with growth retardation and poor scholastic performance. She had multiple fragile fractures started at the age of 15 involving the lower extremities. A physical examination revealed dysmorphic features and intellectual disability with intelligence quotient (IQ) of 36. The initial blood workup showed a picture of distal RTA with hypokalemia, and the radiological imaging confirmed the presence of osteopetrosis and multiple kidney stones. The combination of osteopetrosis with RTA raised the possibility of CA II deficiency. Therefore, computed tomography (CT) of the brain was done and showed intracranial calcification involving the basal ganglia. She was started on potassium chloride and sodium bicarbonate. In addition, she underwent right-sided percutaneous nephrolithotripsy. Her DNA analysis came to show a sequence variant c.232+1G>A, which was detected in both of the CA II genes (homozygous). CONCLUSION: Early recognition of the disease is a key, as an early appropriate treatment institution is essential in order to prevent further complications.

Effect of vitamin d3 on untreated graves' disease with vitamin d deficiency.

OBJECTIVE: Besides its classical role in calcium and bone homeostasis, vitamin D is considered a potent immunomodulator that can affect the pathogenesis of several autoimmune diseases. Our aim is to evaluate the effect of vitamin D correction to a patient with new onset Graves' disease (GD) with an underlying vitamin D deficiency. METHOD: We describe the effect of vitamin D3 on untreated Graves' disease with vitamin D deficiency. RESULTS: A healthy Saudi woman in her 40s sought consultation with a three-month history of palpitation. She denied any history of heat intolerance, weight loss, menstrual irregularity or sweating. She has a history of chronic muscle aches and pains. Physical examination revealed a mild diffusely enlarged and non-tender thyroid gland with no bruit. She had no signs of Graves' ophthalmopathy. In laboratory examinations, the initial thyroid function test, which was done in an outside hospital, revealed a TSH, 0.01 mIU/L; FT4, 22.5 pmol/L and FT3, 6.5 pmol/L. Vitamin D 25-OH level was done in our hospital and showed a result of 26.0 nmol/L with a TSH, 0.013 mIU/L; FT4, 16.7 pmol/L; and FT3, 3.8 pmol/L. TSH receptor antibody was positive. TC-99 m thyroid scintigraphy demonstrated an enlarged thyroid gland with increased radiotracer trapping and heterogeneous distribution. The patient was given only oral cholecalciferol 4000 IU per day since November 2012 (prescribed by an outside hospital) then from May 2013 onwards she was given 50,000 IU per month. Follow-up laboratory exams revealed improved vitamin D levels as well as TSH and FT4. She eventually improved both clinically and biochemically with a satisfactory outcome. CONCLUSION: Vitamin D deficiency may exacerbate the onset and/or development of GD and correction of the deficiency may be able to reverse it. However, further prospective clinical studies will be needed to define the role of vitamin D treatment in GD.