HUM-MOLGEN archive: DIAG (6 messages)

***************************************************************** HUM-MOLGEN DIAGnostics/Clinical Research ***************************************************************** This DIAG message contains 5 professional and 1 patient request: 1) Neuronpathic type III Gaucher disease 2) Spastic paraplegia 3) Carey-Finemam-Ziter syndrome 4) Renal failure and haemolytic Tja antibodies 5) Twins with Albers-Schonberg syndrome 6) Lebers Congenital Amaurosis (Patient request) Replies to message 6 (patient request) should be sent to HUM-MOLGEN. REPLIES TO ALL OTHER MESSAGES SHOULD BE SENT TO THE PERSON MAKING THE REQUEST AND NOT TO HUM-MOLGEN. Carlo Gambacorti, MD, Editor, Harker Rhodes, MD, Assistant Editor Human Molecular Genetics Network Diagnostics/Clinical Research Section ***************************************************************************** ***************************************************************************** 1) Neuronpathic type III Gaucher disease We are interested in clarifying the pathogenesis of the neuronpathic type III Gaucher disease (GD). GD is the most prevalent hereditary metabolic storage disease, and the most common genetic idsorder in individuals of Ashkenazi Jewish ancestry. GD transmitted in an autosomal recessive manner is mostly caused by a deficient activity of the enzyme glucocerebrosidase (GBA). The clinical phenotypes are classified into three groups: non-neuronpathic (type I, which is the most common variant with an incidence of 1 in 30.000, acute neuronpathic (Type II) and chronic (subacute) neuronopathic (type III). ALthough many different point mutations, some insertions, deletions and more complex disease alleles due to recombination events with the GBA pseudogene (GBAP) have been identified, in about 25-35% of all Caucasian GD patients the mutation is still unknown. To get more detailed information of the distribution and frequency of the mutational pattern in European-non-Jewish, Caucasian GD patients we have up to now analyzed the entire GBA coding region in 75 non-Jewish GD patients from whom 11 suffered fom the chronic neuronpathic GD variant. The enzyme replacement therapy which is highly effective in patients with type I has only moderate benefit in patients with type III. As part of our genetic research project we are lookin for further type III GD patients which are mainly characterized by multifocal myoclonus and generalized seizures, horizontal supranuclear gaze palsy, ataxia, spasticity and in the most cases only moderate herpatosplenomegaly and thrombocytopenis. We have established a sequencing procedure for the complete coding GBA as well as for the Nimann-Pick type C- (NPC1)-gene since Niemann-Pick type C is the major differential diagnosis of GD. If you have patients with seizures of unclear etiology in combination with a hepatosplenomegaly, ataxia or supranuclear gaze palsy we are offering a genetic analysis for the GBA and NPC1 gene. We would be grateful also for collaboration with other groups who are aware of type III GD families. Arndt Rolfs, M.D. Professor for Neurology University of Rostock Gehlsheimerstr. 20 D-18055 Rostock Tel.: -49-381-494-9540 FAX.: - 49-381-494-9542 email: arndt.rolfs@medizin.uni-rostock.de ********** 2) Spastic paraplegia We have isolated and characterized the gene involved in a new form of spastic paraplegia and found several mutations. On a collaborative basis, we are currently collecting pure and complicated spastic paraplegia families, both recessive and dominant, as well as sporadic cases with the aim of scanning for mutations and performing phenotype-genotype correlations. Please contact: Dr Giorgio Casari casari@tigem.it ********** 3) Carey-Finemam-Ziter syndrome We have a patient with a possible Carey-Finemam-Ziter syndrome. At birth he had hypotonia, dysmorphic and myopathic face: hypertelorism, epicantus, down labial comisures, Pierre Robin anomaly, bilateral VI and VII nerve palsy. Hypoplastic right thumb without flexion crease, clinodactily bilateral of the 2nd finger, single flexion crease in the left 5th finger and clubbed foot. A tracheotomy was performed at 3 months. Since then he needs mechanical ventilation. Metabolic screening in blood and urine, muscular enzymes, biochemical, hematopoyetic and cytogenetic studies were normal. Muscle biopsy showed minimum and nonspecifics changes. EMG detect normal answer of limbs squeletic muscle, and absence activity of voluntary and reflexes face musculature. Molecular study of myotonic dystrophy was normal. MRI findings included ventricular dilatation, light brain and brainstem atrophy. We would like to know your opinion and extra information about the evolution of this entity (we have the articles: Carey et al.1982, Schimke et al.1993, Baraitser and Reardon 1994) allado@imsb.bcn.es (A.Lladonosa / M.Calvo) ********** 4) Renal failure and haemolytic Tja antibodies We need to know if somebody has experience in kidney transplant in a patient with renal failure and haemolytic Tja antibodies positives. Our patient is 45 years old women with chronic renal failure in heamodyalisis for 10 years and we are interested in making she a renaltransplantation. Dra. Ana Fernandez. fsanchez@CORREO.HPINO.RCANARIA.ES ********** 5) Twins with Albers-Schonberg syndrome: (Apparent patient location: China) Twin A is a 10-month-old girl admitted to a hospital on February 12,1998 for an intermittent fever and cough for 20 days, watery diarrhea for one week, and an increasing anterior frontanelle. She had poor appetite,loss of body weight, untranquil sleep and hyperhidrosis. Vomiting and convulsions were not observed. She can't crawl or turn over her body. She had no history of familial diseases. On physical examination her temperature was36.5deg.C, body weight was 7kg, development was slow, her head circumference was 44cm, anterior frontanelle was3x3cm2 with its tension slightly higher, no occipital atrichia and varicose scalp were found. She was found to have slight nasal obstruction and congestion of throat with her palate arch slightly higher and normal size of tonsil. No abnormality was found in her heart or abdomen except slight respiratory harshness in her two lungs and liver edge was palpable 3cm below the right costal margin and the spleen was palpable 1cm below left costal margin.No abnormality was found in her nervous system except hypomyotonia in her lower extremities. By MR she had slight enlargement of the lateral and 3rd ventricles and a dysplastic, polycystic left kidney.The right kidney was normal by MR but enlarged by ultrasound. Increased density was found in femora, tibiae, fibula, calcaneus, and carpal bone with pachynsis of their cortices and occlusion of their marrow cavities as well as increased pachynsis and hardness of their cranial bones such as middle sphenoid bone wing,sella base,dorsum sellae and both anterior and posterior clinoid processes.These findings brought it into accord with the manifestations of osteopetrosis. Twin A was tentatively diagnosed as: 1. Osteopetrosis(hydrocrania,moderate anemia,slightly slow brain development,slow growth development) 2. Dysplasia of left kidney,renal cyst. 3. Upper respiratory tract infection. 4. Rachitis. Twin B has a similar clinical presentation. We would appreciate advice or assistance treating these patients. They are financially able to travel abroad for therapy. Unit:Pediatric Department,General Hospital of Beijing Military Command Address:No.5 Nan Men Cang,Dongcheng District,Beijing,China(100700) Email address:bmghplhc@public3.bta.net.cn Tel: (010)66721629-8067(O) (010)64049871(H) Fax: (010)66721010 e-mail: jiaosc@cdm.imicams.ac.cn Contact:Professor Liu Ke. -------------------- 6) Lebers Congenital Amaurosis Patient request - please reply to HUM-MOLGEN I am the mother of an 11 month old baby daughter who has been diagnosed with the genetic disorder Lebers Congenital Amaurosis. I am searching for information regarding the current genetic research being conducted into this disorder and would be very grateful for any information or sources. Thank you. ************************************************************************ HUM-MOLGEN - Internet Communication Forumin Human Genetics E-mail: HUM-MOLGEN@nic.surfnet.nl WWW: http://www.informatik.uni-rostock.de/HUM-MOLGEN/ Phone: 020-5664598 (The Netherlands), (206) 386-2101 (USA) Fax: 020-691 6521 (The Netherlands), (206) 386-2555 (USA) ---------------------------------------------------------------------------- --------------- >"copyright HUM-MOLGEN"