Cholesterol side-chain cleavage enzyme activity and cytochrome P-450 content in adrenal mitochondria of a patient with congenital lipoid adrenal hyperplasia (Prader disease)

Koizumi, Satoshi; Seizo, Kyoya; Miyawaki, Toshio; Kawabata, Hiroshi; Funabashi, Takashi; Nakashima, Hitoshi; Nakanuma, Yasuni; Ohta, Goroku; Itagaki, Eiji; Katagiri, Masayuki

doi:10.1016/0009-8981(77)90233-9

Cited by 66 publications

(4 citation statements)

References 7 publications

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“…Patient B was born in spring 1979 (Koizumi et al, 1977; Khoury et al, 2004). She had skin hyperpigmentation since the age of 1.5 months.…”

Section: Patient B (46xx Karyotype)mentioning

confidence: 99%

“…Because mitochondria from affected adrenal and gonads fail to transform cholesterol to pregnenolone, it has been postulated for many years that LCAH disease was due to a defect in the cholesterol side chain cleavage enzyme complex cytochrome P450 (P450scc) (Degenhart et al, 1972; Koizumi et al, 1977; Matteson et al, 1986) which is the first step in steroidogenesis: The conversion of cholesterol to pregnenolone. In searching for such defect, Lin et al (1991), Sakai et al (1994) and Fukami et al (1995) found no mutations in the CYP11A1 gene of affected individuals.…”

Section: Introductionmentioning

confidence: 99%

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Thirty-Eight-Year Follow-Up of Two Sibling Lipoid Congenital Adrenal Hyperplasia Patients Due to Homozygous Steroidogenic Acute Regulatory (STARD1) Protein Mutation. Molecular Structure and Modeling of the STARD1 L275P Mutation

et al. 2016

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Objective: Review the impact of StAR (STARD1) mutations on steroidogenesis and fertility in LCAH patients. Examine the endocrine mechanisms underlying the pathology of the disorder and the appropriate therapy for promoting fertility and pregnancies.Design: Published data in the literature and a detailed 38-year follow-up of two sibling LCAH patients. Molecular structure and modeling of the STARD1 L275P mutation.Setting: University hospital.Patients: Patient A (46,XY female phenotype) and patient B (46,XX female) with LCAH bearing the L275P mutation in STARD1.Interventions: Since early-age diagnosis, both patients underwent corticoid replacement therapy. Patient A received estrogen therapy at pubertal age. Clomiphene therapy was given to Patient B to induce ovulation. Pregnancies were protected with progesterone administration.Main Outcome Measures: Clinical and molecular assessment of adrenal and gonadal functions.Results: Both patients have classic manifestations of corticosteroid deficiency observed in LCAH. Time of onset and severity were different. Patient A developed into a female phenotype due to early and severe damage of Leydig cells. Patient B started a progressive pubertal development, menarche and regular non-ovulatory cycle. She was able to have successful pregnancies.Conclusions: Understanding the molecular structure and function of STARD1 in all steroidogenic tissues is the key for comprehending the heterogeneous clinical manifestations of LCAH, and the development of an appropriate strategy for the induction of ovulation and protecting pregnancies in this disease.

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“…Patient B was born in spring 1979 (Koizumi et al, 1977; Khoury et al, 2004). She had skin hyperpigmentation since the age of 1.5 months.…”

Section: Patient B (46xx Karyotype)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Thirty-Eight-Year Follow-Up of Two Sibling Lipoid Congenital Adrenal Hyperplasia Patients Due to Homozygous Steroidogenic Acute Regulatory (STARD1) Protein Mutation. Molecular Structure and Modeling of the STARD1 L275P Mutation

et al. 2016

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“…A clinical defect of all steroidogenesis was first reported in 1955 18) , and several studies of affected tissue indicated defective conversion of cholesterol to pregnenolone 2 , 19 , 20) , so this disorder was thought to represent an enzymatic defect originally termed '20, 22 desmolase deficiency' 1) . However, studies of DNA from affected patients revealed that the CYP11A1 gene encoding P450scc was normal 21 , 22 , 23 , 24) , and in 1995 this disease was more properly termed 'congenital lipoid adrenal hyperplasia (lipoid CAH)', and it was caused by mutations in the gene encoding StAR 3 , 25) .…”

Section: Steroid Biosynthesismentioning

confidence: 99%

Congenital lipoid adrenal hyperplasia

Kim

2014

Ann Pediatr Endocrinol Metab

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Congenital lipoid adrenal hyperplasia (lipoid CAH) is the most fatal form of CAH, as it disrupts adrenal and gonadal steroidogenesis. Most cases of lipoid CAH are caused by recessive mutations in the gene encoding steroidogenic acute regulatory protein (StAR). Affected patients typically present with signs of severe adrenal failure in early infancy and 46,XY genetic males are phenotypic females due to disrupted testicular androgen secretion. The StAR p.Q258X mutation accounts for about 70% of affected alleles in most patients of Japanese and Korean ancestry. However, it is more prevalent (92.3%) in the Korean population. Recently, some patients have been showed that they had late and mild clinical findings. These cases and studies constitute a new entity of 'nonclassic lipoid CAH'. The cholesterol side-chain cleavage enzyme, P450scc (CYP11A1), plays an essential role converting cholesterol to pregnenolone. Although progesterone production from the fetally derived placenta is necessary to maintain a pregnancy to term, some patients with P450scc mutations have recently been reported. P450scc mutations can also cause lipoid CAH and establish a recently recognized human endocrine disorder.

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“…This disorder is inherited as an autosomal recessive trait, and the affected individuals are all phenotypically female with a severe salt-losing syndrome that is fatal unless treated with steroid replacement therapy (6). Because mitochondria from affected adrenal glands and gonads fail to convert cholesterol to pregnenolone, it was postulated that this disorder might be caused by a defect in SCC (7, 8). However, no mutations have been revealed in the CYP11A1 gene encoding SCC in affected individuals (9,10,11).…”

Section: History and Genetics Of Scc Deficiencymentioning

confidence: 99%

Cholesterol Side-Chain Cleavage Enzyme (SCC) Deficiency

Katsumata¹

2007

Clin Pediatr Endocrinol

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Cholesterol side-chain cleavage enzyme (SCC) catalyzes the conversion of cholesterol to pregnenolone, the first step in the biosynthesis of all steroid hormones. It was once postulated that SCC deficiency would be lethal, but recent studies have established that SCC deficiency is an autosomal recessive disorder caused by inactivating mutations in the CYP11A1 gene. Clinical manifestations include adrenal insufficiency and 46,XY sex reversal due to disrupted steroidogenesis, which are similar to StAR deficiency. Further accumulation of patients with SCC deficiency should clarify the similarities and differences between SCC deficiency and StAR deficiency.

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Cholesterol side-chain cleavage enzyme activity and cytochrome P-450 content in adrenal mitochondria of a patient with congenital lipoid adrenal hyperplasia (Prader disease)

Cited by 66 publications

References 7 publications

Thirty-Eight-Year Follow-Up of Two Sibling Lipoid Congenital Adrenal Hyperplasia Patients Due to Homozygous Steroidogenic Acute Regulatory (STARD1) Protein Mutation. Molecular Structure and Modeling of the STARD1 L275P Mutation

Thirty-Eight-Year Follow-Up of Two Sibling Lipoid Congenital Adrenal Hyperplasia Patients Due to Homozygous Steroidogenic Acute Regulatory (STARD1) Protein Mutation. Molecular Structure and Modeling of the STARD1 L275P Mutation

Congenital lipoid adrenal hyperplasia

Cholesterol Side-Chain Cleavage Enzyme (SCC) Deficiency

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