Sparse hair and multiple endocrine disorders in two women heterozygous for adrenoleukodystrophy

Dumić, M; Gubarev, N.; Šikić, Nada; Roscher, Adelbert A.; Plavšić, Vesna; Filipović‐Grčić, Boris

doi:10.1002/ajmg.1320430515

Cited by 21 publications

(11 citation statements)

References 14 publications

(3 reference statements)

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“…In fact, in the very ®rst report of a patient with AMN, ®rst areolar, then diffuse alopecia was noted from the age of 8 years: a skin biopsy revealed chronic in¯ammatory in®ltrates in the corium (Budka et al, 1976). Additionally, the coexistence of X-ALD and autoimmune endocrine disease has been reported in several patients (Federico et al, 1988;Dumic et al, 1992). Similarly, in patient Z the biochemical defect of X-ALD and an autoimmune polyglandular syndrome were intertwined.…”

Section: Discussionmentioning

confidence: 95%

Signs of testicular insufficiency in adrenomyeloneuropathy and neurologically asymptomatic X‐linked adrenoleukodystrophy: a retrospective study

et al. 1997

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Summary X-linked adrenoleukodystrophy (X-ALD) is characterized by central nervous system demyelination, and impaired steroidogenesis in the adrenal cortex and testis. Most patients develop adrenocortical insuf®ciency. We studied retrospectively the frequency and severity of testicular dysfunction in 26 men with X-ALD. Twenty-one had adrenomyeloneuropathy and ®ve patients were neurologically asymptomatic. In addition to obtaining a routine history and physical examination, we studied plasma levels of testosterone, sex hormone binding globulin, the free androgen index, and the plasma concentrations of dehydroepiandrosterone-sulphate, LH and FSH. In a subset of patients, the testosterone response to hCG and the LH and FSH responses to GnRH were also determined. Clinical signs of gonadal dysfunction were manifested by diminished libido (46%), largely overlapping with erectile dysfunction (58%), and failure of the testes to descend (15%). Physical examination revealed diminished body sexual hair (50%), gynaecomastia (35%), and small testes (12%). Laboratory studies showed low plasma total testosterone levels in 12%, and an insuf®cient increase after stimulation with hCG in 88% (15 of 17 patients tested). Plasma LH concentration was increased in 16%, and the plasma FSH level was elevated in 32%. The response of LH concentrations to GnRH stimulation was abnormally high in 47% (nine of 19 patients studied), and the response of FSH levels was too low in 16% (three of 19 patients tested). In conclusion, in a retrospective study of 26 men' with X-ALD, in 20 some signs of clinical hypogonadism were found. Plasma testosterone values were generally in the normal range, but upon testing of the hypothalamo-pituitary-testis axis some abnormalities became apparent.

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Section: Discussionmentioning

confidence: 95%

Signs of testicular insufficiency in adrenomyeloneuropathy and neurologically asymptomatic X‐linked adrenoleukodystrophy: a retrospective study

et al. 1997

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“…A disturbed hair growth has frequently been reported in men with ALD/AMN [5, 8, 9, 10, 11, 12, 13, 14, 15]. It was the aim of the present study to further characterize the involvement of hair in AMN.…”

Section: Introductionmentioning

confidence: 83%

“…Remarkably, Dumic et al [10]described 2 sisters who were heterozygous carriers of the ALD gene. They had marked alopecia and sparse body hair and one of them showed, in addition, madarosis and sparse eyebrows.…”

Section: Discussionmentioning

confidence: 99%

An X-Linked Gene Involved in Androgenetic Alopecia: A Lesson to Be Learned from Adrenoleukodystrophy

et al. 2000

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Background: Adrenoleukodystrophy (ALD), including its adult variant adrenomyeloneuropathy (AMN), is an X-linked recessive trait characterized by progressive demyelinization of the nervous system. The gene defect involves a peroxisomal transporter protein, resulting in accumulation of very-long-chain fatty acids in the brain and other organs such as the adrenal glands. Affected men show various endocrine disorders. Moreover, disturbances of hair growth are frequently mentioned in reports on ALD/AMN. Objective: This study was performed to delineate further the hair status and type of hair loss in men with AMN. Methods: We examined and documented the status of hair growth in 16 men suffering from AMN. A meticulous history with particular regard to hair changes was taken from all patients and their family members. Results: The age of the patients varied between 27 and 62 years, their mean age was 39.8 years. Twelve men showed male-pattern androgenetic alopecia (AGA), Hamilton grades IV–VIII, 3 men had a female-pattern AGA (Ludwig grade I or II). Ten of the patients with male-pattern AGA had reached Hamilton stage VII or VIII. The remaining scalp hair was unusually scarce and thin in 11 cases, regardless of the grade of AGA. Moreover, in 10 of 16 patients the eyelids showed pronounced madarosis. The remaining body hair was found to be normal. If present, endocrine manifestations had started prior to the onset of alopecia, and in 11 of 12 patients hair loss was apparent before neurological symptoms were noted. Conclusion: ALD/AMN gives rise to two different types of hair loss. Firstly, affected men show diffuse hair loss involving the entire scalp and the eyelashes. Secondly, they tend to develop AGA more frequently and earlier and in a severer form. Paradoxically, pronounced AGA is present although the patients may simultaneously show some degree of hypogonadism. Hence, the X-linked ALD mutation can be taken as a well-defined gene within the polygenic spectrum of genes responsible for AGA. This may be of theoretical importance for the elucidation of the pathogenetic pathways of AGA.

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“…Females heterozygous for ALD may have loss of body hairs and sparse scalp hair [15]. However, more in-depth investiga tions on hair have not yet been performed in those patients; histology from a bald area of the patient reported by Papini et al [8] showed hypotrophy of the hair follicles and hyper plasia of sebaceous glands.…”

mentioning

confidence: 99%

“…It has been found that these chemicals trigger recep tors (so-called peroxisome-proliferator-associated recep tors, PPAR) that are members of the nuclear hormone receptor superfamily, to which retinoic acid receptors and retinoid X receptors belong [17], A target gene for PPAR has been recently identified, that is the acylcoenzyme A oxidase gene, which encodes the key enzyme of the peroxi somal fatty acid (5-oxidation system [15]. Furthermore, a convergence of PPAR and retinoid-dependent signaling pathways is suggested by the facilitating binding of PPAR to cognate response elements by retinoid X receptor a [18], the ligand of which is 9-cis-retinoic acid.…”

mentioning

confidence: 99%

Peroxisome Disorders and Cutaneous Manifestations

Saurat¹,

Itin²

1994

Dermatology

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Beside complex structures such as endoplasmic reticu lum or mitochondria that electron microscopy reveals in human cells, there are organelles bounded by a single membrane; some of these vesicles contain hydrogen-peroxide-generating enzymes and were therefore called 'peroxi somes' to reflect their role in peroxide metabolism. It was later found that enzymes catalyzing the p-oxidation of fatty acids were located not only in mitochondria but also in per oxisomes; in fact the most important metabolic role of the peroxisome seems to be shortening of very-long-chain fatty acids (>22 carbon atoms) and oxidizing di-and trihydroxycoprostanic acids and pristanic acid, a metabolite of phyta nic acid [1], Thus peroxisomes contain enzymatic activities for P-oxidation of fatty acids that are distinct from the mito chondrial pathway.Peroxisomes Papini et al. [8] report the dermatological findings in a patient with X-linked ALD and the metabolic disturbances detectable in the skin sur face lipids.X-linked ALD is a rare peroxisomal disorder, affecting 1/20,000 males. The disease is characterized by an accumu lation of very-long-chain fatty acids because of impaired shortening in peroxisomes. Diagnosis of X-linked ALD is based on the demonstration of high serum levels of verylong-chain fatty acids. Clinical manifestations are central nervous system demyelination and adrenal insufficiency. However, striking variation of the clinical phenotype exists. The gene locus for ALD has been mapped to the ter Prof. J. Ulrich is acknowledged for kindly reviewing the manuscript.

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Sparse hair and multiple endocrine disorders in two women heterozygous for adrenoleukodystrophy

Cited by 21 publications

References 14 publications

Signs of testicular insufficiency in adrenomyeloneuropathy and neurologically asymptomatic X‐linked adrenoleukodystrophy: a retrospective study

Signs of testicular insufficiency in adrenomyeloneuropathy and neurologically asymptomatic X‐linked adrenoleukodystrophy: a retrospective study

An X-Linked Gene Involved in Androgenetic Alopecia: A Lesson to Be Learned from Adrenoleukodystrophy

Peroxisome Disorders and Cutaneous Manifestations

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