Precocious puberty: An experience from a major teaching hospital in Central Saudi Arabia.

Precocious puberty is a developmental process that gives rise to secondary sexual characteristics before the age of 8 years in girls and 9 years in boys. In general, precocious puberty can be classified as central or peripheral. This is a retrospective hospital-based study was conducted at King Khalid University Hospital (KKUH), Riyadh, Saudi Arabia, during the period January 1990 and December 2016. Data were abstracted from the medical records of patients diagnosed with precocious puberty, with special emphasis on age, sex, clinical characteristics, and relevant hormonal assay. A total of 62 patients were diagnosed with Precocious Puberty (PP); 43 had Central Precocious Puberty (CPP) while 19 had peripheral precocious puberty (PPP). The majority of girls with CPP (68%) had idiopathic PP, while pathological causes were found in (50%) of boys. The commonest cause of PPP was congenital adrenal hyperplasia (42%) and chronic hypothyroidism (26%). In conclusion, this study showed that precocious Puberty is a common endocrine problem in our center. The etiology of CPP was idiopathic in the majority of girls while it was caused by CNS pathology in most of the boys in this cohort. Peripheral precocious puberty is not that rare and mainly caused by congenital adrenal hyperplasia or hypothyroidism.

Autoimmune thyroiditis associated with Sanjad-Sakati syndrome: A call for regular thyroid screening.

Sanjad-Sakati Syndrome (SSS) is a rare autosomal recessive disorder characterized by congenital hypoparathyroidism, growth retardation and dysmorphism. Thyroid status of patients with SSS has not been widely explored. Therefore, we aimed to review the occurrence of autoimmune thyroiditis, which is commonly associated with other genetic disorders, in SSS. A retrospective hospital based study was conducted at King Khalid University Hospital, Riyadh, Saudi Arabia, to determine the thyroid status of patients with SSS attending the hospital between 1990 and 2015. Data were extracted from the medical records of patients diagnosed with Sanjad-Sakati syndrome with special emphasis on the clinical features, thyroid function, thyroid antibodies, molecular studies and other relevant investigations. A total of 18 patients with a diagnosis of Sanjad-Sakati Syndrome based on typical clinical features and low parathyroid hormone, were evaluated. Furthermore, molecular study was available on 15 patients; all had homozygous deletion of 12 bp (155-166) in exon 3 of the TCBE gene. In 6 patients the thyroid functions were abnormal (one patient with overt hypothyroidism and five patients with sub clinical hypothyroidism). Thyroid autoantibodies were positive in 4 patients. In conclusion, one third of this cohort with SSS had abnormal thyroid function test attributed mainly to autoimmune thyroiditis. Therefore, we recommend routine screening of patients with SSS for thyroid function and autoimmune antibodies during follow up.

The spectrum of 46XY disorders of sex development in a University centre in Saudi Arabia.

BACKGROUND: The term disorders of sex development (DSD) includes congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical. The spectrum of the 46XY (DSD) is so broad. In this study, we reviewed the clinical spectrum of a cohort of patients with 46XY DSD in a tertiary institute in the Middle East over two decades. OBJECTIVE: To define the clinical spectrum of 46XY DSD in a major teaching hospital, Riyadh, Saudi Arabia. MATERIALS AND METHODS: This is a retrospective, case series hospital-based study. The case notes, laboratory investigations, and imaging studies were reviewed for patients with 46XY DSD over a 20 years period (1989-2010) at King Khalid University Hospital, Riyadh, Saudi Arabia. Molecular genetics were not available in all patients. RESULTS: During the period under review; a total of 56 patients were seen with 46XY DSD due to variable etiologies. Androgen insensitivity syndromes (AIS) and 5-α-reductase deficiency were among the commonest (44.6%), with multiple siblings involvement within the family. Of these, 16 patients were showing variable degrees of insensitivity ranging between complete (n=5, 31.2%) and partial (n=11, 68.8%) insensitivity, whereas in nine patients the diagnosis of 5-α-reductase deficiency was entertained based on hormonal studies. Of interest to see was a high number of patients (n=14, 25%) either with a localized congenital anomalies such as the cloacal anomalies or generalized congenital malformations following the pattern of certain syndromes. CONCLUSION: A wide spectrum of causes were noted. Androgen insensitivity syndrome was the commonest. In Saudi Arabia, where consanguineous mating is high, 5-α-reductase is also a common cause of 46XY DSD.

The clinical pattern of diabetes Insipidus in a large university hospital in the Middle East.

Diabetes insipidus is a rare but serious endocrine disorder. Paediatric patients were evaluated for polyuria at King Khalid University Hospital, Riyadh, Saudi Arabia, over a decade (2000-13). Relevant clinical examination and/or a triad of high serum osmolality, hypernatremia and low urine osmolality due to increased urine output confirmed the diagnosis. Water deprivation test was required in some cases with non-classic presentations. Appropriate brain imaging was performed whenever central diabetes insipidus (CDI) was suspected. Twenty-eight patients, 15 males (53.6%) and 13 females (46.4%), aged 0-17 years (mean: 6 years) were included. The calculated period prevalence was 7 in 10,000. In our cohort, 60.7% (17 of 28 patients) had CDI, 21.4% (6 of 28) were diagnosed with nephrogenic diabetes insipidus (NDI) and 17.9% (5 of 30) had psychogenic polydipsia. CDI was due to variable aetiology. Though CDI was the commonest, NDI was not a rare encounter in our community, possibly because of high consanguineous marriages.

A novel pathogenic mutation of the CYP27B1 gene in a patient with vitamin D-dependent rickets type 1: a case report.

BACKGROUND: Rickets can occur due to Vitamin D deficiency or defects in its metabolism. Three rare genetic types of rickets with different alterations of genes have been reported, including: Vitamin D dependent rickets type 1, Vitamin D dependent rickets type 2 or also known as Vitamin D resistant rickets and 25 hydroxylase deficiency rickets. Vitamin D dependent rickets type 1 is inherited in an autosomal recessive pattern, and is caused by mutations in the CYP27B1 gene encoding the 1α-hydroxylase enzyme. We report here a new mutation in CYP27B1, which lead to Vitamin D dependent rickets type 1. CASE PRESENTATION: We report on a 13-month-old Arabic Saudi girl with Vitamin D dependent rickets type 1 presented with multiple fractures and classic features of rickets. A whole exome sequencing identified a novel pathogenic missense mutation (CYP27B1:Homozygous c.1510C > T(p.Q504X)) which results in a protein truncating alteration. Both parents are heterozygous carriers of the mutation. Based on data search in Human Gene Mutation Database, 63 CYP27B1 alterations were reported: only 28.6% are protein truncating (5 nonsense, 13 frameshift insertions/deletions, 0 gross deletions), while 61.9% are non-truncating (38 missense, 1 small in-frame insertions/deletion), and 9.5% are possible protein-truncating (5 splice, 1 regulatory). CONCLUSION: The deleterious effect of this alteration, which was the only mutation detected in the CYP27B1 common gene of Vitamin D dependent rickets type 1 in the proband, and its autosomal recessive inheritance fashion, both support a pathogenic nature of this mutation as the cause of Vitamin D dependent rickets type 1.

Rickets and osteomalacia in Saudi children and adolescents attending endocrine clinic, Riyadh, Saudi Arabia.

This is a retrospective study in which we report our clinical experience during the period from January 1990 to December 2009, from a paediatric endocrine clinic at King Khalid University Hospital (KKUH), Riyadh, Saudi Arabia. The diagnosis of rickets and oestomalacia was based on clinical, biochemical and radiological data. Eighty-one (34 males and 47 females) children and adolescents with rickets or osteomalacia aged 2 to 18 years (mean; 9.5 years) were evaluated. The commonest causes were nutritional; either low Vitamin D or calcium, or both. In 58 (71.60%) patients, eight patients (9.87%) were due to chronic use of anticonvulsant medications, while five (6.17%) patients were diagnosed to have celiac disease. Non-specific symptoms, such as bone pain and fatigue were the most common presenting symptoms which may indicate that other cases were possibly missed. Lack of direct sun exposure and malnutritional practices were evident. Several genetically inherited disorders were diagnosed; including; hypophosphataemic rickets in three (3.70%), vitamin D-dependent-rickets type 2 in five (6.17%) and pseudohypo-hyperparathyroidism in one (1.23%) child. Rickets was secondary to chronic renal failure in only one patient (1.23%). In conclusion, a diversity of disorders caused rickets or osteomalacia in our series. Paediatricians should be familiar with such different types and able to differentiate them from disorders mimicking rickets. rickets, such as hypophosphatasia, and metaphyseal dysplasias. An active plan should be put in place to prevent rickets and osteomalacia among young age groups.

Ambiguous genitalia: two decades of experience.

BACKGROUND AND OBJECTIVES: Ambiguous genitalia is a complex, medical and social emergency. The aim of this study is to present our experience over two decades, focusing on the pattern and clinical presentation. DESIGN AND SETTING: A retrospective study conducted in the pediatric endocrine clinic at a university hospital Saudi Arabia during the period 1989-2008. PATIENTS AND METHODS: Medical records of children with ambiguous genitalia were reviewed and the genitalia described. RESULTS: Of the 81 children with ambiguous genitalia, 53 (65.4%) patients were genetically females (46XX), with congenital adrenal hyperplasia being the common cause in 51 (96.5%) patients. Hyperpigmentation, variable degrees of salt wasting and a family history of a similar problem helped in diagnosis. Male genetic sex (46XY) was present in only 28 (34.6%) patients with a diversity of causes; multiple congenital anomalies in 9 (32.1%), local anorectal anomalies in 2 (7.1%), congenital adrenal hyperplasia (3-ß-hydroxysteroid dehydrogenase deficiency) in 2 (7.14%), 5-α-reductase deficiency in 4 (14.28%), partial androgen insensitivity in 3 (10.7%), complete androgen insensitivity in 4 (14.28%), and hypogonadotrophin deficiency in 4 (14.3%).Twenty-five (47.2%) of females were wrongly assigned as males, where only two (7.1%) males were wrongly assigned as females. CONCLUSION: Ambiguous genitalia, currently termed disorders of sex development (DSD), is not uncommon in our community. Increased awareness, a detailed history, and a careful physical examination, coupled with appropriate laboratory and radiological investigations aid in early diagnosis and avoid serious sequelae.