Thomas Riebel

Expanded clinical spectrum in hepatocyte nuclear factor 1B-maturity-onset diabetes of the young

AIMS HNF1B-maturity-onset diabetes of the young is caused by abnormalities in the HNF1B gene encoding the transcription factor HNF-1beta. We aimed to investigate detailed clinical features and the type of HNF1B gene anomaly in five pediatric cases with HNF1B-MODY. METHODS From a cohort of 995 children and adolescents with diabetes, we analyzed the most frequent maturity-onset diabetes of the young genes (GCK, HNF1A, HNF4A) including HNF1B sequencing and deletion analysis by quantitative Multiplex-PCR of Short Fluorescent Fragments (QMPSF) if patients were islet autoantibody-negative and had one parent with diabetes or associated extrapancreatic features or detectable C-peptide outside honeymoon phase. Presence and size of disease-causing chromosomal rearrangements detected by QMPSF were further analyzed by array comparative genomic hybridization. RESULTS Overall, five patients had a heterozygous HNF1B deletion, presenting renal disease, elevated liver enzymes, and diabetes. Diabetes was characterized by insulin resistance and adolescent onset of hyperglycemia. Additionally, clinical features in some patients were pancreas dysplasia and exocrine insufficiency (two of five patients), genital defects (three of five), mental retardation (two of five), and eye abnormalities (coloboma, cataract in two of five). One case also had severe growth deficit combined with congenital cholestasis, and another case had common variable immune deficiency. All patients reported here had monoallelic loss of the entire HNF1B gene. Whole genome array comparative genomic hybridization confirmed a precurrent genomic deletion of approximately 1.3-1.7 Mb in size. CONCLUSION The clinical data of our cases enlarge the wide spectrum of patients with HNF1B anomaly. The underlying molecular defect in all cases was a 1.3- to 1.7-Mb deletion, and paired, segmental duplications along with breakpoints were most likely involved in this recurrent chromosomal microdeletion.

Monocarboxylate transporter 8 deficiency: altered thyroid morphology and persistent high triiodothyronine/thyroxine ratio after thyroidectomy

CONTEXT Thyroid hormone transport across the plasma membrane depends on transmembrane transport proteins, including monocarboxylate transporter 8 (MCT8). Mutations in MCT8 (or SLC16A2) lead to a severe form of X-linked psychomotor retardation, which is characterised by elevated plasma triiodothyronine (T(3)) and low/normal thyroxine (T(4)). MCT8 contributes to hormone release from the thyroid gland. OBJECTIVE To characterise the potential impact of MCT8-deficiency on thyroid morphology in a patient and in Mct8-deficient mice. DESIGN Thyroid morphology in a patient carrying the A224V mutation was followed by ultrasound imaging for over 10 years. After thyroidectomy, a histopathological analysis was carried out. The findings were compared with histological analyses of mouse thyroids from the Mct8(-/y) model. RESULTS We show that an inactivating mutation in MCT8 leads to a unique, progressive thyroid follicular pathology in a patient. After thyroidectomy, histological analysis revealed gross morphological changes, including several hyperplastic nodules, microfollicular areas with stromal fibrosis and a small focus of microfollicular structures with nuclear features reminiscent of papillary thyroid carcinoma (PTC). These findings are supported by an Mct8-null mouse model in which we found massive papillary hyperplasia in 6- to 12-month-old mice and nuclear features consistent with PTC in almost 2-year-old animals. After complete thyroidectomy and substitution with levothyroxine (l-T(4)), the preoperative, inadequately low T(4) and free T(4) remained, while increasing the l-T(4) dosage led to T(3) serum concentrations above the normal range. CONCLUSIONS Our results implicate peripheral deiodination in the peculiar hormonal constellation of MCT8-deficient patients. Other MCT8-deficient patients should be closely monitored for potential thyroid abnormalities.

Uncommon synovial cysts in children

Popliteal synovial cysts (Baker’s cysts) are a common occurrence in children and adults. Synovial cysts in other locations and/or with atypical extension are less common and may be confounded with tumors or other medical conditions. In this article we describe the underlying disease, clinical presentation and clinical course in six children with a sudden onset of paraarticular soft tissue masses or non-specific chronic pain. Ultrasound was the initial imaging method used in all cases; this was supplemented by MRI in three patients. Four children were diagnosed to be suffering from juvenile idiopathic arthritis (JIA), one child from Lyme Arthritis, whereas in one child no underlying disease was identified. Well-demarcated hypoechogenic lesions without signs of perfusion extending from the shoulder (two patients), elbow (one patient), hip (one patient), knee (1) or ankle (one patient) far into the adjacent musculature were detected on ultrasonography. A direct connection to the joint was demonstrated in all cases. All synovial cysts in the five arthritic patients resolved rapidly with medical treatment for arthritis, whereas the cyst persisted in the non-JIA patient. Conclusion: Uncommon synovial cysts occur in particular as a complication of arthritis. Ultrasonography is the initial and follow-up imaging method of choice, which can be supplemented by MRI in unusual cases. Apart from treatment for arthritis, no specific therapeutic interventions were required in the present cases.

Intraventricular hemorrhage in a full-term neonate associated with sinus venous thrombosis and homozygosity for the plasminogen activator inhibitor-1 4G/4G polymorphism.

bleeding from the subependymal germinal matrix with subsequent rupture into the cerebrospinal fluid of the ventricles (IVH). Major IVH in term infants appears to be a rare event associated with intrapartum hypoxia and trauma. However, in a considerable proportion of IVH cases of term newborns, attempts to define pathogenetic factors have failed. Here we report severe bilateral IVH occurring in a 6-day-old term newborn without potentially precipitating events who subsequently was found to have sinus venous thrombosis and a prothrombotic genetic disposition.

Xanthogranulomatous pyelonephritis in children: diagnostic and therapeutic aspects

Xanthogranulomatous pyelonephritis (XGP) is a rare, chronic inflammatory disease of the kidneys. It is characterized by destruction of renal parenchyma and accumulation of lipid-laden foamy macrophages. Diffuse and focal forms are known. The condition is mainly observed in middle-aged women, and it is very rare in childhood. Of 32 nephrectomies carried out in children for various diseases in our hospital over the course of 2 years, there were two cases of diffuse XGP. In both cases, the preoperative diagnosis based on ultrasound findings was highly suggestive of XGP. We present the two cases and define the typical ultrasonographic signs for distinguishing XGP from other renal masses. The diagnostic and therapeutic management is discussed and an overview of the literature is given.

A rare location for extratruncular vascular malformation

ZusammenfassungWir berichten über einen zunächst unklaren Tumor im ulnaren Ellenbogenbereich eines 15-jährigen Jungen. Die klinische Untersuchung zeigte eine schmerzhafte Schwellung entlang des N. ulnaris in Ellenbogenhöhe, es bestanden sensible und motorische Ausfälle der linken Hand, der Funktion des N. ulnaris entsprechend. In der Sonographie und MRT-Untersuchung ließ sich ein adäquates Substrat,dem Verlauf des N. ulnaris folgend, darstellen. Die chirurgische Therapie bestand in der Dekompression des Tumors durch Faszienspaltung.Die Histologie zeigte ein den N. ulnaris durchsetzendes kapilläres Hämangiom.Postoperativ wurde oral Cortison (5 mg/kg/Tag) über eine Woche mit wöchentlicher Pause innerhalb von vier Wochen verabreicht.Unter dieser Therapie kam es zur raschen Verkleinerung des Tumors und zur fast vollständigen Wiederherstellung der ulnaren, nervalen Funktion.AbstractWe report on an undefined tumor of the right ulnar side of the elbow in a 15-year-old boy.The clinical examination showed painful swelling in the area of the ulnar nerve at the right elbow as well as sensory and motor deficits of the right hand corresponding to distribution of the ulnar nerve. Ultrasound examination and magnetic resonance imaging showed a tumor along the nerve. Subsequent surgical therapy included tumor decompression by division of the fascia. The histological examination demonstrated a capillary hemangioma that infiltrated the ulnar nerve.After surgery, oral glucocorticoid therapy with cortisone (5 mg/kg per day) was administered over a period of 4 weeks, alternating between 1 week of therapy and 1 week without medication.The result of this combined therapy was a rapid diminution of the tumor and an almost complete restitution of the neural function.

Schilddrüsenknoten bei Kindern und Jugendlichen

ZusammenfassungIm Unterschied zu Erwachsenen sind Schilddrüsenknoten im Kindes- und Jugendalter selten; nur in 0,5% der Kinder können sonographisch Knoten nachgewiesen werden. In den meisten Fällen der in Routineultraschalluntersuchungen diagnostizierten Knoten handelt es sich um gutartige Proliferationen von Schilddrüsenzellen, die keiner weiteren Therapie bedürfen, und nur in einem geringen Prozentsatz lässt sich ein maligner Tumor detektieren. Die vorliegende Übersichtsarbeit erläutert die wichtigsten differenzialdiagnostischen Schritte, die mittels Sonographie und Feinnadelbiopsie eine hohe Sensitivität in der Diagnose der malignen Knoten gewährleisten sollen, bei gleichzeitig möglichst geringer Rate an unnötigen Schilddrüsenoperationen. Eine Zusammenarbeit mit Untersuchern, die über große Erfahrung in der Knotensonographie und der Durchführung der Feinnadelbiopsie verfügen, ist für eine erfolgreiche Diagnostik zwingend erforderlich.AbstractIn contrast to the situation in adults, thyroid nodules are rare in childhood; only 0.5% of pediatric ultrasound surveys detect nodules. In most cases, these nodules represent benign proliferations of thyroid cells and do not require surgical treatment. This review summarizes the various differential diagnostic steps that should lead to identifying those nodules that are likely malignant and need resection by thyroidectomy. The central approaches are ultrasound and fine-needle biopsy. Cooperation with colleagues experienced in performing nodule ultrasound and fine-needle aspiration is essential to reach an appropriate level of correct diagnoses.

Spontaneous regression of a vascular tumor of the skull base--infantile hemangioendothelioma?

Extracerebral masses involving the skull base in children and adolescents are rare. We report on a 4-month-old infant who was diagnosed with a large extracerebral mass in the anterior fossa. Subtotal resection to prevent impending blindness was complicated by almost fatal bleeding. Histopathologically, vessel malformation, epitheloid hemangioendothelioma, and angiosarcoma were possible diagnoses. The residual tumor regressed spontaneously and completely within 6 months after surgery. Retrospectively, histologic and radiologic findings and clinical course prompted the diagnosis of an infantile hemangioendothelioma. To our knowledge, this is the first report on an infantile hemangioendothelioma of the skull base.