RESUMEN
Wolcott-Rallison's syndrome (WRS) is a rare nonautoimmune autosomal recessive disorder characterized by neonatal diabetes mellitus, epiphyseal dysplasia, and growth retardation. This is the most common cause of diabetes mellitus in patients with consanguineous parents. WRS is distinguished from other types of neonatal or early-onset diabetes by clinical characteristics and genetic testing. Here, we report four cases of WRS from South India. All four children reported here were born to consanguineous parents and were diagnosed with neonatal diabetes and skeletal dysplasia. Case 1 is a 13-year-old girl with neonatal diabetes and skeletal dysplasia. Case 2 is a 6-month-old male infant who also has primary hypothyroidism. Case 3 was a girl who lived until the age of 4 years before succumbing to liver failure. Case 4 is an 8-month-old female infant born to a third-degree married couple who presented with neonatal diabetes and diabetic ketoacidosis. Genetic testing revealed that she had WRS, which helps us in the anticipation and early treatment of complications.
RESUMEN
BACKGROUND AND AIM: Neonatal diabetes mellitus (NDM) is a rare monogenic disorder of pancreatic beta cell mass and/or function. In the present study we aimed to evaluate the INS gene mutations in a cohort of children with Permanent Neonatal Diabetes Mellitus (PNDM) and to explore the clinical and genetic characteristics of PNDM caused by INS mutations. METHODS: Direct sequencing of all exons of INS genes was carried out in 189 children with PNDM. Clinical and biochemical data were collected and correlated. The pathogenicity of mutations was determined based on the American College of Medical Genetics and Genomics and Association of Medical Pathology guidelines. RESULTS: Two novel mutations (His34Pro, Leu35Met) in a compound heterozygous state and seven known mutations (Gly32Ser, Phe48Cys, Arg89Cys, Cys96Tyr, Ser98Ile, Try108Asp and Cys109Phe) in the INS gene were identified in 8 patients out of the total of 189 PNDM children studied. Four mutations were involved in defects with disulphide bond formation and hence were in crucial regions of the gene. All the mutations were de novo in origin. CONCLUSIONS: This is the first comprehensive study from India to investigate the insulin gene mutations in PNDM and to show that INS gene mutations also contribute to the causation of PNDM.
Asunto(s)
Diabetes Mellitus/genética , Insulina , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología , Femenino , Humanos , India/epidemiología , Lactante , Recién Nacido , Insulina/genética , Masculino , Mutación , Linaje , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a benign disorder of reversible subcortical vasogenic cerebral edema. CASE CHARACTERISTICS: A 13-yr-old girl presented 4 days after complete recovery from diabetic ketoacidosis with symptoms of headache, altered sensorium, seizures, and visual loss. There was no hypertension or biochemical abnormalities identified. MRI brain showed hyperintense areas in subcortical and periventricular white matter of bilateral fronto-parieto-occipetal lobes, with possible diagnosis of normotensive PRES. OUTCOME: Full recovery without sequelae, following neuro-protection and expectant treatment. MESSAGE: Identifying PRES in diabetic ketoacidosis assists appropriate treatment and prognostication.