Severe Neonatal Cholestasis as an Early Presentation of McCune Albright Syndrome

Coles, Nicole; Comeau, Ian; Muñoz, T. De Haro; Harrington, Jennifer; Mendoza-Londoño, Roberto; Schulze, Andreas; Kives, Sari; Kamath, Binita M.; Hamilton, Jill

doi:10.4274/jcrpe.0110

Cited by 3 publications

(11 citation statements)

References 8 publications

(12 reference statements)

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“…In our case, as in other previously reported neonatal cases of MAS, hyperthyroidism and cardiac dysfunction were present as well. Although hyperthyroidism results from the presence of the Gαs mutation in thyroid tissue that leads to a ligand‐independent activation of the TSH/G‐protein/cAMP pathway with subsequent hyperplasia and hyperfunction of the gland, as well as an increase in thyroxine to triiodothyronine conversion, the pathogenesis of the cardiac dysfunction is more complex.…”

Section: Discussionsupporting

confidence: 89%

“…Nonetheless, an osteopenic bone phenotype, most likely secondary to hypercortisolism, was the major determinant of lethality, with multiple pulmonary marrow emboli originating from fractures of osteopenic ribs. This case and previous reports of MAS with very early onset highlight a syndromic profile of the disease that appears to be unique to the neonatal period, and requires a prompt diagnosis, but may be difficult to recognize. In addition, our case highlights the importance of bone changes that, in the absence of FD or any other direct impact of the disease genotype on bone, may contribute to the lethal outcome of MAS in neonatal patients.…”

Section: Introductionmentioning

confidence: 59%

“…The hepatobiliary dysfunction is another well‐established nonendocrine abnormality in MAS patients . As is the case for GNAS mutation‐associated CS, the hepatobiliary dysfunction occurs when MAS appears early after birth . It tends to progressively wane with age and has never been associated with a functional defect in the synthesis of hepatic factors or with intra‐ or extrahepatic bile ducts obstruction .…”

Section: Discussionmentioning

confidence: 99%

“…Presentation of MAS in neonatal life is a rare and often lethal event . We report here a case of multiorgan disease caused by a gain‐of‐function mutation of GNAS that presented at birth and had an unfavorable outcome.…”

Section: Introductionmentioning

confidence: 98%

“…Presentation of MAS in neonatal life is a rare and often lethal event. (3,(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34) We report here a case of multiorgan disease caused by a gain-of-function mutation of GNAS that presented at birth and had an unfavorable outcome. Major pathological changes were observed in the adrenal glands and liver, consistent with the detection of the greatest concentration of the disease genotype at these sites.…”

Section: Introductionmentioning

confidence: 99%

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Neonatal McCune‐Albright Syndrome: A Unique Syndromic Profile With an Unfavorable Outcome

et al. 2019

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Somatic gain‐of‐function mutations of GNAS cause a spectrum of clinical phenotypes, ranging from McCune‐Albright syndrome (MAS) to isolated disease of bone, endocrine glands, and more rarely, other organs. In MAS, a syndrome classically characterized by polyostotic fibrous dysplasia (FD), café‐au‐lait (CAL) skin spots, and precocious puberty, the heterogenity of organ involvement, age of onset, and clinical severity of the disease are thought to reflect the variable size and the random distribution of the mutated cell clone arising from the postzygotic mutation. We report a case of neonatal MAS with hypercortisolism and cholestatic hepatobiliary dysfunction in which bone changes indirectly emanating from the disease genotype, and distinct from FD, led to a fatal outcome. Pulmonary embolism of marrow and bone fragments secondary to rib fractures was the immediate cause of death. Ribs, and all other skeletal segments, were free of changes of typical FD and fractures appeared to be the result of a mild‐to‐moderate degree of osteopenia. The mutated allele was abundant in the adrenal glands and liver, but not in skin, muscle, and fractured ribs, where it could only be demonstrated using a much more sensitive PNA hybridization probe‐based FRET (Förster resonance energy transfer) technique. Histologically, bilateral adrenal hyperplasia and cholestatic disease matched the abundant disease genotype in the adrenals and liver. Based on this case and other sporadic reports, it appears that gain‐of‐function mutations of GNAS underlie a unique syndromic profile in neonates characterized by CAL skin spots, hypercortisolism, hyperthyroidism, hepatic and cardiac dysfunction, and an absence (or latency) of FD, often with a lethal outcome. Taken together, our and previous cases highlight the phenotypic severity and the diagnostic and therapeutic challenges of MAS in neonates. Furthermore, our case specifically points out how secondary bone changes, unrelated to the direct impact of the mutation, may contribute to the unfavorable outcome of very early‐onset MAS. © 2018 The Authors JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Neonatal McCune‐Albright Syndrome: A Unique Syndromic Profile With an Unfavorable Outcome

et al. 2019

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Hepatic Lesions Associated With McCune Albright Syndrome

Johansen¹,

Haller²,

Thyagarajan

et al. 2019

J. pediatr. gastroenterol. nutr.

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McCune-Albright syndrome (MAS) results from a GNAS gene mutation. It is associated with café au lait macules, fibrous dysplasia, and several endocrinopathies to include gonadotropin-independent precocious puberty, growth hormone excess, Cushing syndrome, thyroid disease, and renal phosphate wasting. It is recognized to be a rare cause of neonatal cholestasis. We describe the hepatic outcome of 3 children with MAS referred to a single national liver unit. All presented with high gamma-glutamyl transpeptidase cholestasis and hepatitis. Cholestasis resolved by 1 year; but hepatic inflammation persisted, and 2 children developed progressive atypical focal nodular hyperplasia and 1 developed hepatoblastoma. This the first reported malignant hepatic lesion associated with MAS. MAS should be considered part of the differential diagnosis of neonatal cholestasis and affected children should be closely monitored for the development of hepatic lesions with regular liver ultrasound and alpha fetoprotein level.

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Neonatal cholestasis as the onset symptom of McCune–Albright syndrome: case reports and a literature review

Fang,

Zhang,

Chen

et al. 2023

Front. Pediatr.

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AimThis study aimed to summarize and show the characteristics and evolutionary process of neonatal cholestasis caused by McCune–Albright syndrome (MAS), as neonatal cholestasis may be the initial manifestation of MAS before other classic clinical features appear.MethodsThe clinical characteristics, treatment methods, and outcomes of three neonatal cholestasis cases caused by MAS in our center were retrospectively studied. In addition, all the reported cases of MAS combined with cholestasis were reviewed and summarized to show the cholestatic features in them.ResultsWe have confirmed three MAS cases in our center, presenting onset symptoms of jaundice, pale stool, and neonatal cholestasis soon after birth. The cholestasis subsided spontaneously at around the sixth month. The literature review showed that the levels of total bilirubin, conjugated bilirubin, ALT, AST, and GGT in neonatal MAS cholestasis cases were 207 μmol/L (range 65–445 μmol/L), 162 μmol/L (range 46–412 μmol/L), 821 U/L (range 85–3,597 U/L), 532 U/L (range 127–3,633 U/L), and 244 U/L (range 79–3,800 U/L), respectively. Liver histology showed canalicular and hepatocellular cholestasis, giant hepatic cell transformation, and bile paucity. Extrahepatic manifestations such as café-au-lait pigmented skin lesions, Cushing's syndrome, hyperthyroidism, renal tubular dysfunction, and skeletal abnormalities could occur simultaneously when jaundice occurred. GNAS mutations had a high positive rate (83.3%–100%) in liver tissue with cholestasis. Neonatal cholestasis caused by MAS could be self-resolved, but hepatic lesions persist and have malignant potential.ConclusionMAS can be one of the causes of neonatal cholestasis, which may be the first manifestation of the disease. Extrahepatic coexisting symptoms of MAS and liver histology can help to distinguish MAS from other etiology of cholestasis. Detecting GNAS mutations in liver tissue may shorten diagnostic time and is of particular interest in the partial and atypical forms of MAS with neonatal cholestasis. Neonatal cholestasis in children with MAS can self-resolve, but liver dysfunction and malignant lesions persist.

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Severe Neonatal Cholestasis as an Early Presentation of McCune Albright Syndrome

Cited by 3 publications

References 8 publications

Neonatal McCune‐Albright Syndrome: A Unique Syndromic Profile With an Unfavorable Outcome

Neonatal McCune‐Albright Syndrome: A Unique Syndromic Profile With an Unfavorable Outcome

Hepatic Lesions Associated With McCune Albright Syndrome

Neonatal cholestasis as the onset symptom of McCune–Albright syndrome: case reports and a literature review

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