Hyperinsulinism and hyperammonaemia.
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Adolescent↗
Biomedical subjects
A al-Ashwal
Publications and source records attributed to A al-Ashwal.
Gender reversal in 46XX congenital virilizing adrenal hyperplasia.
OBJECTIVE: To review the results of gender reversal in six patients with 46XX congenital virilizing adrenal hyperplasia (CVAH). PATIENTS AND METHODS: Fifty-one patients with 46XX CVAH were seen in an 8 year period; 45 were managed by conventional feminizing genitoplasty, but six underwent gender reversal and were managed as males. The clinical decision for gender reversal was made after appropriate counselling and was based primarily on parental choice, this being influenced significantly by a delayed diagnosis in four patients. Surgical management consisted of gonadectomy, excision of Müllerian structures and staged hypospadias repair/ chordee correction in four patients, and circumcision in two completely masculinized children. RESULTS: All six boys are well adjusted to their gender of rearing, with ages ranging from 3 years to 16.5 years (mean 8.5) at the time of review. Two children have normal penises and four have a satisfactory result after two-stage repair of hypospadias/chordee. CONCLUSION: Most patients with 46XX CVAH are preferably raised as females and require a feminizing genitoplasty. However, the clinical decision may be influenced by many factors, including delay in diagnosis, social bias and the premium on male rearing in certain communities. When male rearing is chosen, early gonadectomy and excision of Müllerian structures, together with staged hypospadias repair, gives satisfactory results.
Adolescent↗
A novel mutation in the deoxyribonucleic acid-binding domain of the vitamin D receptor causes hereditary 1,25-dihydroxyvitamin D-resistant rickets.
Mutations in the vitamin D receptor (VDR) result in hereditary 1,25-dihydroxyvitamin D3-resistant rickets (HVDRR), an autosomal recessive disease caused by target organ resistance to the action of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. In this study, we investigated the molecular basis of HVDRR in a child from Saudi Arabia who was previously shown to be resistant to 1,25-(OH)2D3 action, but whose cultured skin fibroblasts exhibited normal [3H]1,25-(OH)2D3 binding. Using the PCR, exons 2 and 3 of the VDR gene that encode the DNA-binding region of the receptor were amplified and sequenced. A novel point mutation at nucleotide 252 in exon 2 of the VDR was identified. This missense mutation (GGC to GAC) resulted in the conversion of glycine to aspartic acid at amino acid position 46 (G46D), located at the base of the first zinc finger. This single base change was introduced into wild-type VDR complementary DNA by site-directed mutagenesis, and the mutant VDR was then expressed in COS-1 cells. The expressed mutant VDR displayed a normal binding affinity (Kd = 1.2 x 10(-10) mol/L) for [3H]1,25-(OH)2D3 as determined by Scatchard analysis. However, the mutant VDR was shown to have reduced binding affinity for DNA by DNA-cellulose chromatography. In COS-7 cells cotransfected with a vitamin D response element-chloramphenicol acetyltransferase reporter construct and the mutant VDR complementary DNA expression vector, the mutant VDR was unable to activate gene transcription in cells treated with up to 100 nmol/L 1,25-(OH)2D3. Restriction fragment length polymorphism analysis using MwoI restriction digests of exon 2 demonstrated that the affected child is homozygous for the mutation, whereas the child's father is heterozygous and a carrier of the defective allele. In conclusion, a new mutation was identified in exon 2 of the VDR gene. This mutation, which occurs in the first zinc finger of the DNA-binding domain of the receptor, blocks 1,25-(OH)2D3 action and leads to the syndrome of HVDRR.
Base Sequence↗
Persistent hyperinsulinemic hypoglycemia of infancy: experience with 28 cases.
Twenty-eight infants with persistent hyperinsulinemic hypoglycemia of infancy (PHHI) were seen during a 10-year period. There were 13 males and 15 females. Their age at time of presentation ranged from a few hours to 6 months. Consanguinity was reported in 20 cases (71.4%). One family had two affected siblings and two affected cousins, another had three affected siblings and one affected cousin, and three others had lost siblings because of hypoglycemia and seizures. The primary clinical presentation was jitters and seizures in association with hypoglycemia. The diagnosis was suspected when the therapeutic glucose requirement was found to be more than 12 mg/kg/min and also when there was a good response to glucagon after exclusion of metabolic and storage diseases. A high insulin-to-glucose ratio was noted for all patients. Twenty-two had near-total (90%) pancreatectomy; the result was excellent in all but four, who required supplemental medical therapy. Five patients were treated medically, and one patient's family refused treatment. Twelve patients sustained moderate to severe brain injury before referral. There were no deaths, and only one patient had evidence of malabsorption after the pancreatectomy. PHHI correlates well with consanguinity and family history. Clinical awareness is essential to permit early diagnosis and prompt medical and supportive therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗