17α-hydroxylase/17,20 carbon chain lyase deficiency caused by p.Tyr329fs homozygous mutation: Three case reports

AbstractBackground:Congenital hyperinsulinism results in refractory hypoglycemia. If a therapy with diazoxide has been unresponsive this has been treated by subtotal pancreatectomy in the past. This therapeutic option poses an increased risk of developing diabetes at a later stage. There have been a few case reports on the use of sirolimus in such situations in the recent past.Case presentation:Our patient was started on sirolimus very early, on day 29 of life and at the age of 14 months is doing well on sirolimus therapy. His growth and development have been good and he has not had any major complications so far. Genetic testing showed a novelKCNJ11homozygous mutation on next generation sequencing and the parents were heterozygous carriers.Conclusions:We report the successful use of sirolimus in the management of diazoxide unresponsive congenital hyperinsulinism with diffuse pancreatic involvement. We believe this is the youngest patient to be initiated on sirolimus so far.

Download Full-text

Late-onset riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (MADD): case reports and epidemiology of ETFDH gene mutations

BMC Neurology ◽

10.1186/s12883-019-1562-5 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 4

Author(s):

Wei Chen ◽

Youqiao Zhang ◽

Yifeng Ni ◽

Shaoyu Cai ◽

Xin Zheng ◽

...

Keyword(s):

Dehydrogenase Deficiency ◽

Late Onset ◽

Southern China ◽

Case Reports ◽

Lipid Storage ◽

Chinese Family ◽

Homozygous Mutation ◽

Muscle Enzymes ◽

Lipid Storage Myopathy ◽

Southern Min

Abstract Background Multiple acyl-CoA dehydrogenase deficiency (MADD) is a riboflavin-responsive lipid-storage myopathy caused by mutations in the EFTA, EFTB or ETFDH genes. We report a Chinese family of Southern Min origin with two affected siblings with late-onset riboflavin-responsive MADD due to a homozygous c.250G > A EFTDH mutation and review the genetic epidemiology of the c.250G > A mutation. Case presentation Both siblings presented with exercise-induced myalgia, progressive proximal muscle weakness and high levels of serum muscle enzymes and were initially diagnosed as polymyositis after a muscle biopsy. A repeat biopsy in one sibling subsequently showed features of lipid storage myopathy and genetic analysis identified a homozygous mutation (c.250G > A) in the ETFDH gene in both siblings and carriage of the same mutation by both parents. Glucocorticoid therapy led to improvement in muscle enzyme levels, but little change in muscle symptoms, and only after treatment with riboflavin was there marked improvement in exercise tolerance and muscle strength. The frequency and geographic distribution of the c.250G > A mutation were determined from a literature search for all previously reported cases of MADD with documented mutations. Our study found the c.250G > A mutation is the most common EFTDH mutation in riboflavin-responsive MADD (RR-MADD) and is most prevalent in China and South-East Asia where its epidemiology correlates with the distribution and migration patterns of the southern Min population in Southern China and neighbouring countries. Conclusions Mutations in ETFDH should be screened for in individuals with lipid-storage myopathy to identify patients who are responsive to riboflavin. The c.250G > A mutation should be suspected particularly in individuals of southern Min Chinese background.

Download Full-text

Homozygous Mutation in the FANCD2 Gene Observed in a Saudi Male Infant with Severe Ambiguous Genitalia

Case Reports in Endocrinology ◽

10.1155/2021/6686312 ◽

2021 ◽

Vol 2021 ◽

pp. 1-4

Author(s):

Aida Al Jabri ◽

Nusaybah Al Naim ◽

Abeer Al Dossari

Keyword(s):

Gene Mutation ◽

Fanconi Anemia ◽

Case Reports ◽

Bone Marrow Failure ◽

Skin Pigmentation ◽

Gene Mutations ◽

Male Infant ◽

Ambiguous Genitalia ◽

Homozygous Mutation ◽

Inherited Disease

Fanconi anemia (FA) is a rare autosomal recessive inherited disease caused by gene mutations that are primarily involved in the response to or repair of DNA damage. FA characterizes by multiple congenital abnormalities and malformations including growth retardation, renal agenesis, absence of radial bones and thumbs as well, progressive bone marrow failure, irregular skin pigmentation patterns, and increased susceptibility to cancer. FANCD2 gene mutation is believed to be one of the causative mutations in Fanconi anemia, and despite many case reports that link the FANC gene mutation to multiple congenital anomalies and disease, there is no case report found to link it with genitalia abnormalities. In our paper, we report a male Saudi infant who presented to the endocrine clinic at the age of 9 months with severe ambiguous genitalia and found that he carries a homozygous variant mutation in the FANCD2 gene and we face a challenge to treat this patient since there was no previous similar case.

Download Full-text

Hemolytic Uremic Syndrome Due to Methylmalonic Acidemia and Homocystinuria in an Infant: A Case Report and Literature Review

Children ◽

10.3390/children8020112 ◽

2021 ◽

Vol 8 (2) ◽

pp. 112

Author(s):

Vasiliki Karava ◽

Antonia Kondou ◽

John Dotis ◽

Georgia Sotiriou ◽

Spyridon Gerou ◽

...

Keyword(s):

Hemolytic Uremic Syndrome ◽

Early Onset ◽

Renal Damage ◽

Early Recognition ◽

Case Reports ◽

Brain Magnetic Resonance Imaging ◽

Methylmalonic Acidemia ◽

Delayed Response ◽

Homozygous Mutation ◽

Uremic Syndrome

Methylmalonic acidemia and homocystinuria cobalamin C (cblC) type is the most common inborn error of the intracellular cobalamin metabolism, associated with multisystem involvement and high mortality rates, especially in the early-onset form of the disease. Hemolytic uremic syndrome (HUS) is a rare manifestation and needs to be distinguished from other causes of renal thrombotic microangiopathy. We describe a case of a 3-month-old infant, with failure to thrive, hypotonia and pallor, who developed HUS in the setting of cblC deficit, along with dilated cardiomyopathy, and presented delayed response to optic stimulation in visual evoked potentials, as well as enlarged bilateral subarachnoid spaces and delayed myelination in brain magnetic resonance imaging. Renal damage was reversed, while neurodevelopmental profile and eye contact improved after supplementation with parenteral hydroxycobalamin, oral folic acid, betaine and levocarnitine. Homozygous mutation of c.271dupA in the MMACHC gene was ultimately detected. In this report, we highlight the diagnostic challenges as well as the significance of early recognition and multidisciplinary management of this unusual condition. A brief review of published case reports of early-onset cblC deficit and related HUS is depicted, pointing out the initial clinical presentation, signs of renal damage and outcome, MMACHC gene type of mutations and accompanying extra-renal manifestations.

Download Full-text

17α-Hydroxylase/17,20-Lyase Deficiency Caused by a Novel Homozygous Mutation (Y27Stop) in the Cytochrome CYP17 Gene

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2005-0136 ◽

2005 ◽

Vol 90 (7) ◽

pp. 4362-4365 ◽

Cited By ~ 16

Author(s):

Karsten Müssig ◽

Simone Kaltenbach ◽

Fausto Machicao ◽

Christiane Maser-Gluth ◽

Michaela F. Hartmann ◽

...

Keyword(s):

Homozygous Mutation ◽

Lyase Deficiency ◽

Cyp17 Gene

Download Full-text

Homozygous Mutation G539R in the Gene for P450 Oxidoreductase in a Family Previously Diagnosed as Having 17,20-Lyase Deficiency

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2008-0051 ◽

2008 ◽

Vol 93 (9) ◽

pp. 3584-3588 ◽

Cited By ~ 54

Author(s):

Eli Hershkovitz ◽

Ruthi Parvari ◽

Stefan A. Wudy ◽

Michaela F. Hartmann ◽

Larissa G. Gomes ◽

...

Keyword(s):

Mass Spectrometry ◽

Gas Chromatography ◽

Gas Chromatography Mass Spectrometry ◽

Homozygous Mutation ◽

P450 Oxidoreductase ◽

Lyase Deficiency ◽

Redox Partner ◽

Chromatography Mass Spectrometry ◽

Urinary Steroid

Context: Very few patients have been described with isolated 17,20-lyase deficiency who have had their mutations in P450c17 (17α-hydroxylase/17,20-lyase) proven by DNA sequencing and in vitro characterization of the mutations. Most patients with 17,20-lyase deficiency have mutations in the domain of P450c17 that interact with the electron-donating redox partner, P450 oxidoreductase (POR). Objective: Our objective was to clarify the genetic and functional basis of isolated 17,20-lyase deficiency in familial cases who were previously reported as having 17,20-lyase deficiency. Patients: Four undervirilized males of an extended Bedouin family were investigated. One of these has previously been reported to carry mutations in the CYP17A1 gene encoding P450c17 causing isolated 17,20-lyase deficiency. Methods: Serum hormones were evaluated before and after stimulation with ACTH. Urinary steroid metabolites were profiled by gas chromatography-mass spectrometry. Exons 1 and 8 of CYP17A1 previously reported to harbor mutations in one of these patients and all 15 coding exons of POR were sequenced. Results: Gas chromatography-mass spectrometry (GC-MS) urinary steroid profiling and serum steroid measurements showed combined deficiencies of 17,20-lyase and 21-hydroxylase. Sequencing of exons 1 and 8 of CYP17A1 in two different laboratories showed no mutations. Sequencing of POR showed that all four patients were homozygous for G539R, a previously studied mutation that retains 46% of normal capacity to support the 17α-hydroxylase activity but only 8% of the 17,20-lyase activity of P450c17. Conclusion: POR deficiency can masquerade clinically as isolated 17,20-lyase deficiency.

Download Full-text

Disseminated lymphocytoma cutis. Case reports of miliarial and nodular types

Archives of Dermatology ◽

10.1001/archderm.100.4.459 ◽

1969 ◽

Vol 100 (4) ◽

pp. 459-464 ◽

Cited By ~ 1

Author(s):

S. J. Self

Keyword(s):

Case Reports

Download Full-text

Case Reports Link ADHD Stimulants to Skin Eruptions

Pediatric News ◽

10.1016/s0031-398x(11)70320-4 ◽

2011 ◽

Vol 45 (12) ◽

pp. 10

Author(s):

SHERRY BOSCHERT

Keyword(s):

Case Reports

Download Full-text

Abstract #347: Correlation of Serum Levels of Pro-insulin With Tumor Size of Insulinomas: Two Case Reports

Endocrine Practice ◽

10.1016/s1530-891x(20)44091-1 ◽

2006 ◽

Vol 12 ◽

pp. 9

Author(s):

Marielba Agosto Mujica

Keyword(s):

Tumor Size ◽

Case Reports ◽

Serum Levels

Download Full-text

Bowel ischaemia after endovascular aneurysm repair

VASA ◽

10.1024/0301-1526/a000698 ◽

2018 ◽

Vol 47 (4) ◽

pp. 273-277

Author(s):

Christopher Lowe ◽

Oussama El Bakbachi ◽

Damian Kelleher ◽

Imran Asghar ◽

Francesco Torella ◽

...

Keyword(s):

Case Reports ◽

Endovascular Aneurysm Repair ◽

Artery Occlusion ◽

Bibliographic Databases ◽

Bowel Ischaemia ◽

Prophylactic Measures ◽

Increased Risk ◽

Prisma Statement ◽

Meta Analyses ◽

Aneurysm Repair

Abstract. The aim of this review was to investigate presentation, aetiology, management, and outcomes of bowel ischaemia following EVAR. We present a case report and searched electronic bibliographic databases to identify published reports of bowel ischaemia following elective infra-renal EVAR not involving hypogastric artery coverage or iliac branch devices. We conducted our review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement standards. In total, five cohort studies and three case reports were included. These studies detailed some 6,184 infra-renal elective EVARs, without procedure-related occlusion of the hypogastric arteries, performed between 1996 and 2014. Bowel ischaemia in this setting is uncommon with an incidence ranging from 0.5 to 2.8 % and includes a spectrum of severity from mucosal to transmural ischaemia. Due to varying reporting standards, an overall proportion of patients requiring bowel resection could not be ascertained. In the larger series, mortality ranged from 35 to 80 %. Atheroembolization, hypotension, and inferior mesenteric artery occlusion were reported as potential causative factors. Elderly patients and those undergoing prolonged procedures appear at higher risk. Bowel ischaemia is a rare but potentially devastating complication following elective infra-renal EVAR and can occur in the setting of patent mesenteric vessels and hypogastric arteries. Mortality ranges from 35 to 80 %. Further research is required to identify risk factors and establish prophylactic measures in patients that have an increased risk of developing bowel ischaemia after standard infra-renal EVAR.

Download Full-text