Congenital lipoid adrenal hyperplasia with 46, XY karyotype and male external genitalia: Two cases and literature review / 中华内分泌代谢杂志

Congenital lipoid adrenal hyperplasia (CLAH) is a rare autosomal recessive disorder, which is characterized by adrenal insufficiency and 46, XY sex reversal. Two cases of CLAH with 46, XY karyotype exhibited male external genitalia were reported to explore the clinical and genetic features. A retrospective analysis of CLAH with relevant literatures was performed.

A study of congenital lipoid adrenal hyperplasia in two pedigrees / 中华内分泌代谢杂志

The clinical features and laboratory data of two patients with congenital lipoid adrenal hyperplasia (CLAH)were collected. The genomic DNA was extracted from the peripheral blood white cells in the two patients and their family members and the STAR gene was screened for mutations by PCR and Sanger sequencing. Patient 1 was a girl aged 2 years and 8 months,and she visited us because of continual cyanosis for more than two years. Physical examination showed no obvious pigmentation or clitoral hypertrophy,and Tanner stage was B1P1. Clinical examination revealed serum ACTH 1 284.1 pg/ml and 17α-hydoxyprogesterone(17-OHP)0.54 ng/ml, with Karyotype 46, XX. Genetic analysis showed compound heterozygous mutations of c.201_202delCT and c.229C>T in the STAR gene. Her father carried heterozygous c.201_202delCT mutation, and her mother showed heterozygous c.229C>T mutation. Patient 2 was a girl aged 22 years and referred to us because of dark skin for more than 21 years. Physical examination revealed generalized hyperpigmentation,with Tanner stage B5P2. Hormone examination showed ACTH>2 000 pg/ml and serum cortisol 0.77μg/dl. Karyotype analysis revealed 46,XX. Genetic analysis found compound heterozygous mutations of c.64+1G>C and c.707_708delinsCTT in the STAR gene,which descended from her father and mother respectively. Of note,c.64+1G>C is a novel splicing mutation of STAR gene.

Rare type of congenital adrenal hyperplasia / 中华实用儿科临床杂志

Congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic disease due to glucocorticoid biosynthesis enzyme deficiency,in addition to the common types such as 21-hydroxylase,11 β-hydroxylase deficiency,also include rare types such as 3 β-hydroxysteroid dehydrogenase deficiency,17α-hydroxylase deficiency and congenital lipoid adrenal hyperplasia (CLAH).These rare types of CAH have multiple clinical manifestations,which are easily missed or misdiagnosed.This article focus on molecular genetics,pathophysiology,clinical manifestations and treatment principles of above 3 rare types of CAH.

Mutation analysis of steroid acute regulatory protein gene in a patient affected with congenital lipoid adrenal hyperplasia / 中华内分泌代谢杂志

Objective To analyze the clinical characteristic s of an infant with congenital lipoid adrenal hyperplasia (CLAH),and to sequence the acute regulatory protein (steroid acute regulatory,StAR) gene of the infant patient and her pedigree.Methods Physical examination,laboratory tests,and imaging examination of the 11-month-old patient with CLAH were collected.DNA was extracted from blood samples of the patient and her parents.The 7 exons of StAR gene were amplified by PCR and then sequenced.Results Dark skin,girl vulva,and one each 1.0 cm×1.0 cm palpable lump in inguinal area bilaterally were observed.The adrenocorticotropic hormone (ACTH) was 253 pg/ml,cortisol was 27.6 nmol/L at 8 am,17-hydroxyprogesterone was 3 nmol/L.Uhrasound showed that sign of testicular ultrasonography existed in bilateral inguinal regions.Karyotype analysis showed 46,XY.Sequencing of PCR amplified fragments showed that there were two heterozygous mutations c.229C ＞ T,p (Gln77X) and C.659A＞G,p (His220Arg) of StAR gene in this patient.By rectifying the disturbance of electrolyte,and treating with hydrocortisone and 9α fludrocortisone,etc,the patient has been stable so far.Conclusion The patient presents typical clinical manifestations.Two heterozygous mutations including c.229C ＞T,p (Gln77X) from maternal and C.659A＞G,p (His220Arg) from paternal of StAR gene were detected.Wherein the c.659A＞G,p.(His220Arg) as a novel point mutation of StAR gene,has not been reported so far.

Congenital Lipoid Adrenal Hyperplasia Developed in a Brother and Sister / 대한주산의학회잡지

Congenital lipoid adrenal hyperplasia (lipoid CAH) is an autosomal recessive disorder characterized by severe adrenal insufficiency. Clinical findings of patients are salt loss, hypoglycemia, pigmentation and male sex reversal. And also the baby with inadequate treatment may result in sudden death from adrenal crisis. We report the case of lipoid CAH developed in siblings with a brief review of associated literatures.

A Case of Congenital Lipoid Adrenal Hyperplasia: Early Diagnosis by Using Computed Tomography / 대한소아내분비학회지

Congenital lipoid adrenal hyperplasia, the most severe form of congenital adrenal hyperplasia, is caused by mutations in the steroidogenic acute regulatory protien (StAR). It is characterized by failure of synthesis of all three classes of adrenal steroids and massive accumulation of lipids and cholesterol in the adrenal cortex. The computed tomography (CT) unequivocally delineated massively enlarged adrenal glands of fat-tissue attenuation, enabling early diagnosis and replacement therapy. We report a case of congenital lipoid adrenal hyperplasia, in which CT established that lipoid deposition at the adrenal cortex disappeared after the adrenal hormone replacement therapy.

A Molecular Genetic Study with EcoRII Restriction Enzyme on the Steroidogenic Acute Regulatory Protein (StAR) Gene / 대한소아내분비학회지

The molecular defect of congenital lipoid adrenal hyperplasia has been discovered to be in the transport of cholesterol into mitochondria due to defective regulatory protein called "Steroidogenic Acute Regulatory Protein (StAR)", while the enzyme P450scc itself is normal. This study with EcoRII restriction enzyme aimed at elucidating more conveniently the molecular defect in the StAR gene. The genomic DNAs were extracted from their peripheral blood. We amplified the exon 7, hot spot, of the StAR gene with 1 set of primers by Polymerase Chain Reaction (PCR). Subsequently, a PCR product corresponding to target sequence (~437 bps) from the patient and her father have been sequenced by automatic sequence analyzer. The PCR-RFLP (Restriction Fragment Length Polymorphism) analysis after restriction digestion with EcoRII restriction enzyme was also performed on 12% polyacrylamide gel electrophoresis. The mutation was identified in the exon 7 of the StAR gene, substituting C for T at codon 258, consequently replacing glutamine by stop codon. This mutation alters EcoRII restriction site. In addition, we obtained the good result of PCR-RFLP (Restriction Fragment Length Polymorphism) analysis on 12% polyacrylamide gel electrophoresis. Therefore, the PCR-RFLP (Restriction Fragment Length Polymorphism) analysis with EcoRII restriction enzyme can be easily utilized to screen carrier, diagnose the patient prenatally or postnatally.

The Molecular Genetic Study Using Automatic Sequence Analyzer on the Steroidogenic Acute Relulatory Protein(StAR) Gene / 대한소아내분비학회지

PURPOSE:The lesion of Congenital Lipoid Adrenal Hyperplasia has been suggested to be in the 1st step of steroidogenesis of conversion of cholesterol to pregnenolone by P450scc. In 1995, however, the molecular defect of this disease has been located in the transport of cholesterol into mitochondria due to defective regulatory protein called Steroidogenic Acute Regulatory Protein(StAR), while the enzyme P450scc itself is normal. This genetic study using automatic sequence analyzer aimed at elucidating the molecular defect in the StAR gene of the two patients. METHODS:This study was performed on the two patients of Congenital Lipoid Adrenal Hyperplasia. Both children were phenotypically females. However, one turned out to have a karyotype of 46, XY, the other 46, XX. Genomic DNAs were extracted from their peripheral blood. We amplified the last exon, hot spot, of the StAR gene using 1 set of primer, S4, 5'-CCT GGC AGC CTG TTT GTG ATA G-3' AS4, 5'-CCT CAT GTC ATA GCT AAT CAG TG-3'. Subsequently, one PCR product have been directly sequenced by dideoxy termination method, and also the other products(patient's and her father's) have been sequenced by automatic sequence analyzer. RESULTS:The mutation was identified in the last exon of the StAR gene, substituting T for A at codon 258, replacing glutamine by stop codon in the two unrelated Korean patients with congenital lipoid adrenal hyperplasia. One patient were found to be homozygote, but the other to be heterozygote for the mutation. CONCLUSIONS:These results indicate that Korean children with congenital lipoid adrenal hyperplasia may be genetically identical as in Japanese. But, we discovered that the hot spot, codon 258, are not always homozygote. We want to emphasize the different point, and to say that we did experiece the automatic sequence analyzer successfully.

A Case of Congenital Lipoid Adrenal Hyperplasia

Congenital lipoid adrenal hyperplasia is the rarest type among salt losing types of congenital adrenal hyperplasia. The defect of this disorder is in the cholesterol side chain cleavage enzyme(P450SCC)which converts cholesterol to pregnenolone. W experienced a case of 20,22 desmolse deficiency in a 21-day old phenotypically female who was admitted to our hospital due to lethargy and dark skin pigmentation. The characteristic findings were decreased serum cortisol, aldosterone, testosterone, increased ACTH. The ACTH and hCG stimulation test were performed and there were no response. The sex chromosomal analysis showed made XY. One year later after hormone therapy, growth and development are normal.