Syndrome of Congenital Insulin Resistance Caused by a Novel INSR Gene Mutation

Mutations in the INSR gene result in rare inherited syndromes causing insulin resistance, such as leprechaunism (Donohue syndrome), Rabson-Mendenhall syndrome and insulin resistance type A. Leprechaunism is an autosomal recessive disorder associated with extreme insulin resistance that leads to hyperinsulinemia, impaired glucose homeostasis, fasting hypoglycemia and postprandial hyperglycemia. Impaired insulin action causes prenatal and postnatal growth retardation. Lipoatrophy, dysmorphic facies, hypertrichosis, macrogenitosomia and hypertrophy of internal organs are also present. A male infant with congenital insulin resistance was born at term after a normal pregnancy with a weight of 1905 g (<3 c), a length of 48 cm (<3 c), and an Apgar score of 10. Intrauterine growth retardation, transient hypoglycemia, pneumonia, urinary tract infection and heart defects [patent foramen ovale (PFO); patent ductus arteriosus (PDA)] were diagnosed after birth. At 5 weeks of age, he was admitted to the regional hospital with severe fever, diarrhea and dehydration. Hyperglycemia was observed (672 mg/dL), and insulin was administered. He was referred to a hospital at 7 weeks of age for suspected neonatal diabetes and hypertrophic cardiomyopathy. The physical examination revealed a loud systolic heart murmur, tachycardia, tachypnea, dysmorphic facies, hypertrichosis, acanthosis nigricans, hypotonia, swollen nipples and enlarged testicles. Glycemic fluctuations (50-250 mg/dL) were observed. The serum insulin concentration was high (maximum 1200 IU/mL) at normoglycemia. Ultrasound of the heart confirmed progressive hypertrophic cardiomyopathy. Leprechaunism was confirmed by genetic analysis of INSR, in which a novel c.320C>G; p. Thr107Arg homozygous missense mutation was found in exon 2.

Combination 1550 nm non-ablative fractional resurfacing and laser hair removal for treatment of Becker's nevi in skin types III-VI.

OBJECTIVES: Becker's nevus is a cosmetically bothersome benign hamartoma typically associated with basal layer hyperpigmentation and hypertrichosis. We herein present the largest case series characterizing treatment parameters and clinical outcomes of combined 1550 nm non-ablative fractional resurfacing and laser hair removal (long-pulsed neodymium-doped yttrium aluminum garnet or alexandrite) in the treatment of Becker's nevus. This is also the largest case series of laser treatment of Becker's nevus in Fitzpatrick skin types V and VI. METHODS: We performed a retrospective review of patients treated between 2016 and 2021. Clinical photographs were graded by three independent physicians using a 5-point visual analog scale. RESULTS: Twelve patients (mean age: 24.8 years, Fitzpatrick skin types III-VI) were treated for Becker's nevus on the face (4) or the trunk and/or extremities (8). Four patients were Fitzpatrick skin types V or VI. On average, patients received 5.3 treatments in 1-4-month intervals. Ten of the 12 patients had concomitant laser hair removal preceding same-day non-ablative fractional resurfacing (n = 7 with long-pulsed 1064 nm neodymium-doped yttrium aluminum garnet and n = 3 with long-pulsed 755 nm alexandrite). The number of treatments with each modality was determined by patient satisfaction with improvement in hyperpigmentation and hypertrichosis. At follow-up, which ranged from 6 to 40 weeks (mean 10.5 weeks), patients were given a mean improvement score of 51%-75%. No long-term adverse events were encountered in either group. Limitations include a small sample size and a lack of long-term follow-up. CONCLUSION: Combination 1550 nm non-ablative fractional resurfacing and laser hair removal is safe and efficacious in the cosmetic reduction of hyperpigmentation and hypertrichosis associated with Becker's nevus, including those with Fitzpatrick skin types V and VI.

Hair and Nail Conditions: Hypertrichosis and Hirsutism.

Hypertrichosis and hirsutism can be signs of underlying conditions, some of which may be life-threatening. They also can result in significant psychosocial distress for patients. Hypertrichosis refers to excessive hair growth beyond normal variation for a patient's age, sex, or race or for a particular body area. Hirsutism refers to an abnormal excess of hair growth solely in androgen-dependent areas of the body in females. The standard for hirsutism assessment is the modified Ferriman-Gallwey (mFG) score. Hirsutism can be idiopathic or associated with endocrine conditions, most commonly polycystic ovary syndrome (PCOS). Evaluation for underlying causes may be indicated depending on the clinical presentation. For premenopausal patients with an abnormal hirsutism score (ie, mFG score of 8 or greater), a serum total testosterone level should be obtained. If the level is normal in patients with moderate to severe hirsutism and/or evidence of a hyperandrogenic endocrine condition, an early morning serum total testosterone level and a free testosterone level should be obtained. An elevated total testosterone level indicates a hyperandrogenic state, and further testing is needed to determine if this is due to PCOS or another endocrine condition. Hair removal options for patients with hirsutism include temporary methods, electrolysis, and laser treatments. Pharmacotherapies include topical creams, combination oral contraceptives, and antiandrogens. Referral to an endocrinologist may be indicated if an underlying endocrine condition is suspected.

Atypical comorbidities in a child considered to have type 1 diabetes led to the diagnosis of SLC29A3 spectrum disorder.

INTRODUCTION: SLC29A3 spectrum disorder is an autosomal, recessively inherited, autoinflammatory, multisystem disorder characterized by distinctive cutaneous features, including hyperpigmentation or hypertrichosis, hepatosplenomegaly, hearing loss, cardiac anomalies, hypogonadism, short stature, and insulin-dependent diabetes. CASE PRESENTATION: Herein, we report a 6-year-old boy who presented with features resembling type 1 diabetes mellitus, but his clinical course was complicated by IgA nephropathy, pure red cell aplasia, and recurrent febrile episodes. The patient was tested for the presence of pathogenic variants in 53 genes related to monogenic diabetes and found to be compound heterozygous for two SLC29A3 pathogenic variants (p. Arg386Gln and p. Leu298fs). CONCLUSION: This case demonstrated that SLC29A3 spectrum disorder should be included in the differential diagnosis of diabetes with atypical comorbidities, even when the distinctive dermatological hallmarks of SLC29A3 spectrum disorder are entirely absent.

Approach to the Patient With Pseudoacromegaly.

Pseudoacromegaly encompasses a heterogeneous group of conditions in which patients have clinical features of acromegaly or gigantism, but no excess of GH or IGF-1. Acromegaloid physical features or accelerated growth in a patient may prompt referral to endocrinologists. Because pseudoacromegaly conditions are rare and heterogeneous, often with overlapping clinical features, the underlying diagnosis may be challenging to establish. As many of these have a genetic origin, such as pachydermoperiostosis, Sotos syndrome, Weaver syndrome, or Cantú syndrome, collaboration is key with clinical geneticists in the diagnosis of these patients. Although rare, awareness of these uncommon conditions and their characteristic features will help their timely recognition.

Case of melorheostosis associated with ipsilateral verrucous epidermal nevus, linear connective tissue nevus, diffuse hyperpigmentation and hypertrichosis: A fortuitous coincidence?

Melorheostosis (MEL) is a rare benign bone disorder that can be associated with several anomalies, including vascular abnormalities, nevus sebaceus, unilateral nevoid telangiectasia, linear scleroderma and hypertrichosis. We report the case of a 6-year-old patient who showed an unusual co-occurrence of bone hyperostosis and different skin lesions affecting the same side of the body: MEL, verrucous epidermal nevus, connective tissue nevus, linear scleroderma-like disorder, hyperpigmentation and hypertrichosis. The spatial co-occurrence of these conditions made us speculate as to whether they originated from a common genetic mechanism or if their co-occurrence was completely accidental.

Oliver McFarlane syndrome and choroidal neovascularisation: a case report.

BACKGROUND: Oliver McFarlane syndrome (OMS) is a rare autosomal recessive disorder characterised by pigmentary chorioretinal atrophy with no previous reports of choroidal neovascularisation (CNV). MATERIAL AND METHODS: We describe the history, findings of clinical examination, retinal imaging and electrodiagnostic studies, and the treatment of a patient with CNV secondary to OMS. CASE DESCRIPTION: CNV secondary to OMS was diagnosed in a ten-year-old white female who presented with reduced visual acuity and a macular haemorrhage in her right eye. CNV was confirmed on optical coherence tomography. She was initially treated with a single injection of intravitreal bevacizumab and 2 years later with an injection of intravitreal ranibizumab for a recurrence. Although macular scarring secondary to the CNV was observed, her vision has stabilised and she continues to be closely monitored. CONCLUSION: We report the first case of CNV secondary to OMS and its successful treatment with intravitreal anti-vascular endothelial growth factor injections.

A novel 3' untranslated region mutation in the SLC29A3 gene associated with pigmentary hypertrichosis and non-autoimmune insulin-dependent diabetes mellitus syndrome.

BACKGROUND: Pigmentary hypertrichosis and non-autoimmune insulin-dependent diabetes mellitus (PHID) is one of the rare H syndrome diseases mainly characterized by hyperpigmentation, hypertrichosis, sensorineural hearing loss, cardiac complications, developmental delay, and diabetes mellitus (DM). Mutations in the coding regions of the SLC29A3 gene that encodes for an equilibrative nucleoside transporter (ENT3) have been reported to cause the phenotypic spectrum of the H syndrome. Disease-causing mutations in the untranslated regions (UTRs) of the SLC29A3 gene have not been previously described in the literature. The aim of the study is to describe and assess the pathogenicity of a novel 3'UTR mutation in the SLC29A3 gene associated with the PHID phenotype in two Turkish patients. METHODS: The mutation was identified by a targeted gene approach. To understand the pathogenicity of this 3'UTR mutation, RNA and protein expression studies were performed by using the quantitative real-time polymerase chain reaction method and western blotting, respectively, using fibroblasts cultured from the patients' skin biopsies. RESULTS: SLC29A3 and ENT3 expression levels were both decreased in the patients compared to controls matched for passage numbers, RNA, and protein extraction methods. CONCLUSIONS: A novel 3'UTR mutation in the SLC29A3 gene is associated with the PHID syndrome, highlighting a potentially new pathological mechanism for this disease. The involvement of the 3'UTR has not been previously established in any of the H syndrome disease cluster or in any complex syndrome of DM.

Identification of a novel homozygous frameshift mutation in SLC29A3 gene in a case with H syndrome from Iran.

H syndrome is a rare monogenic autosomal recessive disease with characteristic cutaneous findings and multisystem involvement. The aim of this study is to present an Iranian patient with H syndrome and to describe a novel frameshift mutation in SLC29A3 gene. The patient was diagnosed with a few small areas of hyperpigmentation and accompanying hypertrichosis in the lumbar area of her back. Her clinical phenotypes included short stature, hepatosplenomegaly, facial widespread bilateral telangiectatic lesions, bilateral hypertrophy of the parotid gland, upper extremity flexion contracture, elevated inflammatory markers (ESR, CRP) and diabetes mellitus. The identification of a novel homozygous frameshift mutation (c.307_308delTT, p.F103Ter) in SLC29A3 gene, together with the characteristic clinical manifestations of H syndrome, provided accurate diagnosis for this patient.

The First Reported Case of Fibrous Hamartoma of Infancy with Hyperhidrosis and Hypertrichosis in Korea.

Fibrous hamartoma of infancy (FHI) is a rare entity with a benign nature. The typical clinical features are a single, slowly growing, painless mass on the trunk that appears within the first 2 years of life. We report a 13-month-old boy who presented with a plaque on the lower back since 4 months of age. The plaque had gradually become larger and firm, and hyperhidrosis and hypertrichosis were noticed. No visible connection between the spinal cord and the lesion was found in radiologic studies, indicating a disease other than spinal dysraphism. Histopathological findings showed well-defined fibrous trabeculae, mature adipose tissue, and primitive mesenchymal cells, all consistent with FHI. This is the first case of FHI presenting with hyperhidrosis and hypertrichosis reported in Korea.

Porfiria cutánea tarda en un paciente con hepatitis C / Porphyria cutanea tarda in a patient with hepatitis C

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