Ballinger-Wallace Syndrome

Maternally transmitted syndrome with diabetes mellitus (DM), neurosensory deafness, and ophthalmic abnormalities.

Maternally Inherited Diabetes Mellitus-Deafness Syndrome; Noninsulin-Dependent Diabetes Mellitus with Deafness.

Unknown. DM affects 5% of the population in the Western world. It consists of a genetically heterogeneous group of disorders with glucose intolerance being the common clinical feature. More than 60 different hereditary DM syndromes have been described. Maternally inherited DM and deafness represents a unique syndrome within this grouping.

The mitochondrial form of DM and deafness is inherited in a heterogeneous pattern. The syndrome has been associated with a 10.4-kb mitochondrial DNA (mtDNA) deletion and a mutation in nucleotide 3243, altering the mitochondrial tRNA for leucine. The deletion is unique because it is maternally transmitted, removes the light strand origin of mtDNA replication, inhibits mitochondrial protein synthesis, and is not associated with the hallmarks of other mtDNA deletion syndromes (ptosis, ophthalmoplegia, or muscle weakness).

The mtDNA deletion causes a defect in the mitochondrial oxidative phosphorylation, which impairs pancreatic islet cell function. Once the mitochondrial adenosine triphosphate (ATP) production of the islet cells falls below the level required for appropriate glucose “sensing,” DM ensues. The exact mechanism of protein synthesis inhibition is unclear.

Based on clinical features consistent with the disorder (see below). Pathologic glucose tolerance test, audiometry testing, and ophthalmic examination. The pedigree demonstrates maternal inheritance.

The syndrome is characterized by DM (noninsulin and insulin dependent with age of onset between 20 and 30 years), progressive bilateral neurosensory hearing loss, and impaired vestibular function (unsteady gait, dizziness). Ophthalmologic examination reveals pigmentary retinal degeneration (normal visual acuity with concentric narrowing of the visual fields) and eventually external ophthalmoplegia. Seizures and dysarthria have also been reported.

Obtain a detailed clinical history and a thorough clinical examination to determine the systemic involvement of DM (coronary artery disease, arterial hypertension, nephropathy, neuropathy, retinopathy) and the degree of hearing loss and vestibular impairment. Review the treatment for DM (actual blood glucose level, glycemia control, diabetic medication regimen). Evaluate cardiac function (electrocardiography, exercise electrocardiography, echocardiogram), neurologic function (peripheral and autonomic neuropathy), and renal function (urea, creatinine, electrolytes, glomerular filtration rate). Blood work should include a complete blood count.

Diabetic patients have a higher perioperative morbidity and mortality compared to nondiabetic patients. Diabetic patients should receive priority on all scheduled operating lists. Perioperative monitoring of blood glucose and cardiac, pulmonary, and renal function is essential. Meticulous attention must be paid to patient positioning because of peripheral neuropathy, and increased propensity to tissue damage. Patients with autonomic neuropathy are unable to compensate for positional changes, and sympathectomy because of central neuraxial blockade may result in severe arterial hypotension. Remember that these patients are at increased risk for ileus and aspiration (especially patients suffering from diabetic ketoacidosis or autonomic neuropathy with delayed gastric emptying because of gastric atony) and require a rapid sequence induction. Use lactate-containing solutions (lactated Ringer solution) carefully (or avoid them altogether) because they may exacerbate a preexisting lactic acidosis in hyperglycemic states.

Patients on preoperative long-acting sulfonylureas (glibenclamide) and metformin should be switched to short-acting sulfonylureas (glipizide, gliclazide, tolbutamide) 3 days before operation. Patients on long-acting insulin should be changed to a combination of shortand intermediate-acting insulins in the preoperative period. The choice of regimen for perioperative diabetic management depends on the type of diabetes (insulin or noninsulin dependent), preoperative diabetic control, and type of surgery. Patients controlled with diet or oral antidiabetic drugs usually will require insulin for moderate and major surgery. Insulin-dependent patients will require intravenous insulin for all but the most minor procedures. Two common approaches are used: separate infusions of insulin and glucose with potassium, or a single combined glucose-potassium insulin infusion (GPI). Both require regular blood sugar monitoring (1-2 hourly) and adjustment of infusion rates.

Wolfram Syndrome: Autosomal recessive inherited syndrome with the defect on the short arm of chromosome 4 often referred to as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) syndrome. However, only insulin-dependent DM and bilateral progressive optic atrophy are required for the diagnosis. DM commonly precedes the other signs of DIDMOAD and often develops earlier in these patients (age 3-10 years) when compared to Ballinger-Wallace syndrome. An inherited abnormality of thiamine metabolism may be responsible for the multisystemic manifestations of DIDMOAD syndrome. Some patients present with sideroblastic or megaloblastic anemia, neutropenia, or thrombocytopenia, which responded well to treatment with thiamin. Cardiomyopathy, hypothyroidism, mental retardation, nystagmus, and seizures may be present. Diabetes insipidus is caused by a loss of vasopressin neurons in the supraoptic nucleus and a defect in processing vasopressin precursors. In addition to the aforementioned precautions before anesthesia, the presence of diabetes insipidus may require preoperative correction and careful intraoperative and postoperative monitoring of the patient's fluid balance.

Rogers Syndrome: Autosomal recessive inherited disorder. Triad of thiamine-responsive anemia (macrocytic anemia, sometimes with moderate thrombocytopenia), DM, and sensorineural deafness. Some cases may have a situs inversus viscerum totalis or a cardiac septal defect. Preoperative evaluation may include echocardiography and subacute bacterial endocarditis prophylaxis. Situs inversus should be kept in mind for all invasive procedures.