Clinical, Endocrine, and Molecular Genetic Analysis of a Large Cohort of Saudi Arabian Patients with Laron Syndrome.

BACKGROUND/AIMS: Laron syndrome (LS) is an autosomal recessive disease characterized by marked short stature and very low serum IGF-1 and IGFBP-3 levels. This study assessed the clinical and endocrine features alongside determining the growth hormone receptor gene (GHR) mutation in Saudi Arabian patients with LS in order to establish whether or not a genotype/phenotype correlation is evident in this large cohort. SUBJECTS AND METHODS: A total of 40 Saudi Arabian patients with a suspected diagnosis of LS were recruited and subjected to a full clinical and endocrine investigation together with direct sequencing of the coding regions of the GHR gene. RESULTS: GHR mutations were identified in 34 patients from 22 separate nuclear families. All 34 molecularly confirmed patients had the typical clinical and endocrinological manifestations of LS. Eleven different mutations (9 previously unreported) were detected in this cohort of patients, all inherited in an autosomal recessive homozygous form. No genotype/phenotype correlation was apparent. CONCLUSION: The identification of pathogenic mutations causing LS will be of tremendous use for the molecular diagnosis of patients in Saudi Arabia and the region in general, with respect to prevention of this disease in the forms of future carrier testing, prenatal testing, premarital screening and preimplantation genetic diagnosis.

Continuous subcutaneous insulin infusion in type 1 diabetic Saudi children. A comparison with conventional insulin therapy.

OBJECTIVE: To assess the efficacy and effectiveness of continuous subcutaneous insulin infusion (CSII) therapy in type 1 diabetic Saudi children in comparison with conventional insulin (CI) therapy. METHODS: Continuous subcutaneous insulin infusion was initiated in 14 Saudi children with type 1 diabetes mellitus (T1DM) through insulin pump therapy between October 2002 and June 2004. All children were followed at the Diabetes Clinic, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia. The patients were initially on CI therapy, which is usually defined as 2 or fewer insulin injections per day before shifting them to CSII. The patients were trained on carbohydrates counting and started on continuously basal insulin infusion aside from the meal and high blood glucose correction insulin boluses. RESULTS: The patients included in the study had T1DM for a mean duration of 6 years. The age of the children ranged from 4-18 years. They were followed on insulin pump therapy for a mean duration of 10 months. There was a significant reduction in hemoglobin A1c, mean blood glucose level, total insulin requirement, frequency of hypoglycemic episodes and frequency of diabetic ketoacidosis (DKA) events during CSII therapy. CONCLUSION: Continuous subcutaneous insulin infusion improved the glycemic control in diabetic Saudi children with decreased frequency of hypoglycemic episodes and DKA events. Long follow-up studies are needed to confirm these results.

The syndrome of septo-optic dysplasia in Saudi children.

OBJECTIVE: To describe the clinical, ophthalmological, endocrinological and radiological features of 10 Saudi children with the syndrome of septo-optic dysplasia and hypothalamic hypopituitarism. METHODS: All patients underwent complete ophthalmological and endocrinological evaluation at the Pediatric Endocrine Clinics, King Faisal Specialist Hospital and Research Center and King Fahad National Guard Hospital, Riyadh, Kingdom of Saudi Arabia, from October 1999 through to May 2004. The hormonal evaluation included growth hormone, adrenocorticotrophic hormone, thyroid stimulating hormone, gonadotropin and anti diuretic hormone testing, and the neuroradiological assessment included brain magnetic resonance imaging or computed tomogram scanning, or both. RESULTS: The current age of patients ranged from 18- months to 5-years. The mean age of initial presentation for endocrine evaluation was 14-months. Hormonal studies indicated that all children had multiple pituitary hormone deficiencies (2 or more of the pituitary hormones were deficient). Ten children had growth hormone deficiency, 8 had thyroid stimulating hormone deficiency, 8 had adrenocorticotrophic hormone deficiency, 2 children were suspected to have gonadotropin deficiency and central diabetes insipidus was present in one patient. Pendular nystagmus and impaired vision were common initial signs. All children had bilateral optic nerve hypoplasia. Neuroradiologic findings were variable. Eight children had absent septum pellucidum, 3 had pituitary gland hypoplasia, 2 had pituitary stalk dysplasia (pituitary stalk was either attenuated or not visualized), 2 had absent corpus callosum and one had absent posterior pituitary high intensity signal. All patients were replaced with appropriate hormonal replacement therapy. Two male children had micropenis which responded to testosterone therapy. CONCLUSION: The syndrome of septo-optic dysplasia is commonly associated with hypothalamic hypopituitarism including anterior and posterior pituitary hormonal deficiencies. Early diagnosis of this syndrome is critical as the hormonal deficiencies can be life threatening.

Prevalence and characteristics of celiac disease in type I diabetes mellitus in Saudi Arabia.

OBJECTIVE: To examine the prevalence of celiac disease in young patients in the Kingdom of Saudi Arabia with type I diabetes mellitus. METHODS: Serum gliadin immunoglobulin (Ig) A and reticulin IgA antibody determination was performed in 123 patients with type I diabetes mellitus attending the pediatric diabetic clinic at King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia between 1995 and 1996. RESULTS: Elevated serum gliadin and reticulin IgA antibodies were found in the sera of 10 (8.1%) of the 123 diabetic children; none had gastrointestinal symptoms. Six of the 10 subjects had jejunal biopsy, which showed total villus atrophy. Four subjects did not undergo jejunal biopsy. The gender ratio of the biopsy positive is 5 male:1 female. All subjects with IgA positive were put on gluten free diet and normalized in a few months. CONCLUSION: The maximum prevalence of celiac disease in our population was 8.1% based on immunological marker and the minimum was 4.9% based on antibodies and biopsy results.

Persistent hyperinsulinemic hypoglycemia of infancy in 38 children.

OBJECTIVE: To describe the clinical, biochemical, radiological and electrophysiological features of 38 Saudi children with persistent hyperinsulinemic hypoglycemia of infancy that have been followed since 1983. METHODS: Data from 38 patients followed at King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia from 1983 through to 2002 was retrospectively analyzed. Persistent hyperinsulinemic hypoglycemia of infancy was diagnosed on the basis of high intravenous glucose requirement, high insulin to glucose ratio, negative urinary ketones and normal tandem mass spectrometry. The patients were assessed radiologically by brain magnetic resonance imaging, computed tomography, or both and electrophysiologically by brain stem auditory evoked potential, visual evoked response and electroencephalogram. The patients who failed medical therapy had subtotal pancreatectomy. RESULTS: The patients were severely hypoglycemic and intolerant to fast. Hypoglycemic convulsion was the most commonly presenting complaint. Eighteen patients were developmentally delayed and 14 of them had brain atrophy. All patients, except nine, did not respond to medical treatment and had surgery. Four pancreatectomized patients developed diabetes and 2 had malabsorption. One patient was treated medically during childhood and developed diabetes and weight gain during adolescence. CONCLUSION: Persistent hyperinsulinemic hypoglycemia of infancy is a relatively common and serious disease among Saudi children. Early medical intervention is necessary to avoid neurological damage in our patients who are severely hypoglycemic and medical therapy unresponsive. Surgically and probably medically treated patients are at high risk of developing diabetes that could be the natural outcome of this disease.

Long-term follow up of carbonic anhydrase II deficiency syndrome.

OBJECTIVE: To describe the long term clinical, biochemical and radiological features of 35 Saudi Arabian children with carbonic anhydrase II deficiency syndrome who have been followed at King Faisal Specialist Hospital and Research Center, Riyadh since 1979. METHODS: The records of these patients were retrospectively evaluated. The diagnosis was based on the clinical and the radiological evidence of the disease. Carbonic anhydrase II level was measured in 9 patients. RESULTS: Clinically, these patients had typical facial features, growth failure and varying degrees of psychomotor retardation. Biochemically, all children had renal tubular acidosis that was of distal type in the majority of them. Radiologically, this syndrome was characterized by metyphyseal osteopetrosis and intracranial calcification that was progressive in 2 patients. Five patients were blind secondary to optic nerve entrapment and 2 patients developed anemia and secondary erythropoesis due to bone marrow involvement. Nineteen patients had attained the final adult height; the mean adult height was 146 cm (-3 standard deviation) in 11 females and 152 cm (-4 standard deviation) in 8 males. Two patients were married and had clinically and radiologically normal children. CONCLUSION: The syndrome of carbonic anhydrase II deficiency is usually benign in nature and compatible with long term survival, however it can progress and involve the cranial nerves. Close clinical and neurological assessment of these patients is mandatory to early detect and manage potential serious complications.