The Case Files

Welcome to the Case Files!
The Case Files is an anecdotal collection of emergency medicine cases to enable physicians and researchers to find clinically important information on unusual conditions.

Case reports should focus on:

  • Unusual side effects or adverse interactions.
  • Unusual presentations of a disease.
  • Presentations of new and emerging diseases, including new street drugs.
  • Findings that shed new light on a disease or an adverse effect.

Comment on a case or submit your own case following the instructions in the Submissions box to the right.

Tuesday, May 23, 2017


A 51-year-old woman presented to the emergency department with severe mid-abdominal pain that had begun early that morning and progressively worsened. The patient also reported having loose bloody stools, bouts of nausea, and several episodes of vomiting yellow bilious fluid.

Her medical history was negative for similar episodes. Past medical history was significant for asthma, gastroesophageal reflux disease, hyperlipidemia, hypertension, colonic polyps, constipation, and thyroid disease. Surgical history included cholecystectomy, C-section, and Nissen fundoplication. Social history was significant for smoking. Her vital signs were within normal limits, but complete blood counts showed white blood cells were elevated to 16.58 thous/uL with left shift of neutrophils, 11.6%. Abdominal CT scan demonstrated the classic target-like sign (photo), indicating an intussusception of the ileocolic area with secondary partial bowel obstruction. (BMJ Case Rep 2014 Jun 20; 2014, doi: 10.1136/bcr-2013-203156; Radiol Med 2015;120[1]:105.)

Sudden Pain Onset

Clinically, intussusception presents with sudden onset of episodic cramping and abdominal pain. It may be associated with emesis, blood in stool, and an elongated mass of the upper right quadrant. (Acta Chir Belg 2015;115[5]:327.) Diagnosis is made using CT scan, and it should show the classic “bull's eye” appearance of the affected segment of bowel. (Radiol Med 2015;120[1]:105.) Diagnosis of intussusception can reliably be done through CT, and the imaging is 83.3% sensitive. Other diagnostic tools still being used to identify intussusceptions include plain abdominal x-rays, barium enema, colonoscopy, and ultrasound. (Acta Medica [Hradec Kralove] 2015;58[2]:66.)​

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Pre-operative CT scan showing the characteristic bull's eye sign for intussusception on patient's left side.

A gastrografin enema was performed in this patient, which resolved the intussusception and her symptoms. A pre-operative colonoscopy was performed, and two polyps were biopsied. One was located in the cecum and did not show any hyperplastic or adenomatous changes. The second was biopsied from the transverse colon, and was a tubular adenoma. The patient's previous history is significant for other polyps, none of which showed dysplastic or inflammatory changes.

A right hemicolectomy was performed two days after presentation to the ED to prevent recurrence of the intussusception. Studies have suggested the use of radiologic findings to distinguish idiopathic from secondary intussusception, which may be useful in determining the need for surgery. (Radiol Med 2015;120[1]:105.) The resected segment was 25 cm of the colon beginning from the cecum, with an attached 7 x 1 x 0.9 cm appendix and a 4.5 cm portion of the terminal ileum. The mucosa was pink-tan without masses or ulceration. Interestingly, there was an approximately 2.5 cm intussusception. Typical therapy consists of segmental bowel resection in adults to prevent recurrence and to eliminate an underlying malignancy. (Radiol Med 2015;120[1]:105.) Conversely, intussusception in children is idiopathic in 75 to 90 percent of the cases, and the majority resolve using air or fluid pressures — barium or air enema. (Acta Chir Belg 2015;115[5]:327; J Nat Sci Biol Med 2015;6[1]:208.)

The Link to Celiac Disease

Intussusception is the most common cause of small bowel obstruction in young children. When signs of bowel obstruction or acute abdomen are present, there is a high clinical suspicion. (Acta Chir Belg 2015;115[5]:327.) Intussusception is a rare discovery in adults, representing five percent of all reported cases and one to five percent of intestinal obstructions. (Korean J Gastroenterol 2013;61[1]:17; Gastroenterology Insights 2012;4[e4]:57.) Several types of intussusception occur along the length of the bowel, but the most common type is ileo-colic, accounting for approximately 90 percent of the cases. (Acta Chir Belg 2015;115[5]:327.)

Intussusception is most often the result of a focal or lead point that forces the bowel to involute into itself, causing a portion of the gut to telescope into the adjacent segment of the bowel. (J Coll Physicians Surg Pak 2013;23[4]:287.) The associated mesentery becomes congested and can result in small bowel obstruction, ischemia, bowel necrosis, or perforation leading to peritonitis and sepsis. (BMJ Case Rep 2014;2014, doi: 10.1136/bcr-2013-203156; Acta Chir Belg 2015;115[5]:327; J Nat Sci Biol Med 2015;6[1]:208.) Lead points include but are not limited to neoplasms, polyps, or Meckel's diverticulum; the former being responsible for 65 to 70 percent of adult cases and the latter being more common in young children. Very few cases of intussusception in adults are idiopathic. The exact mechanism of intussusception varies, but the leading theory suggests that lesions or irritants to the bowel wall can serve as a focus point for the bowel wall to involute on itself with continued peristaltic activity. (Acta Medica [Hradec Kralove] 2015;58[2]:66.)

An interesting association mentioned was the linkage between intussusception and celiac disease. This patient did not display symptoms or have a history of celiac disease upon questioning, but this detail should not be overlooked in other cases because intussusception may be the originating clue to suggest celiac disease. (BMJ Case Rep 2014;2014, doi: 10.1136/bcr-2013-203156.)

This patient's post-operative ileus was resolved by encouraging frequent ambulation. Dietary restrictions were placed until bowel function returned to normal. She was discharged one week later, and was doing well at follow-up.

Wednesday, May 10, 2017

​A previously healthy 17-year-old girl presented to the ED with one month of intermittent, burning epigastric pain associated with nausea and vomiting. Pain was worsened by spicy, greasy foods, and alleviated by sparkling water. She said she came to the ED because the pain had persisted for a while and was interfering with her life. The patient denied fevers, recent travel, or a change in bowel movements. She admitted to traveling to Nicaragua many times in her life and to an unintentional 20-pound weight gain over the past year.​

Vitals at presentation were a heart rate of 83 bpm, temperature of 36.6°C, blood pressure of 114/62 mm Hg, and respiratory rate of 20 bpm. Physical exam was significant only for a slightly enlarged nontender thyroid gland and mild epigastric and right upper quadrant tenderness to palpation. The RUQ tenderness on exam prompted a bedside ultrasound to explore for cholelithiasis, choledocolithiasis, cholecystitis, and hepatitis. It showed a gallbladder with a Phrygian cap that appeared normal and a white hyperechoic lesion in the liver that prompted an abdominal ultrasound by an ultrasound tech and a reading by a radiologist.

The patient received one dose of antacids for her abdominal pain, which she said resolved her symptoms. The ultrasound revealed a normal gallbladder and a liver mass characterized as an ill-marginated 3.5 x 5.3 cm echogenic focus in the left lobe of the liver with peripheral hypoechogenicity with internal central vascularity shown by color Doppler. (Shown.) The radiologist recommended an MRI with liver mass protocol to evaluate the lesion. Labs sent by the ED were unremarkable, including a normal coagulation profile, CBC, and CMP.

The patient was admitted for further workup of the unspecified liver mass, for which the differential diagnosis included hemangioma, adenoma (though the patient was not on oral contraceptives), hepatocellular carcinoma, hydatid cyst, and focal nodular hyperplasia. Fortunately for her, the MRI showed focal nodular hyperplasia (FNH). (Shown.) She was seen by the pediatric gastroenterology team, and was discharged with follow-up to monitor the FNH.

FNH is the second most common liver tumor. (Cancer 1980;46[2]:372.) It is believed to occur as a response by hepatocytes to underlying congenital AV malformation. Women with FNH are at risk of developing hemorrhagic foci within the liver when on oral contraceptives. FNH is generally benign other than that increased risk. (Mod Pathol 1989;2[5]:456.) It is important to characterize a liver lesion as FNH to save a patient from unnecessary liver biopsy. The patient had a benign liver lesion, but this case still highlights the important role bedside ultrasound can play in the evaluation, workup, and management of common symptoms presenting to the ED.

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Dr. Gilbert is a first-year emergency medicine resident in the Jackson Health System at the University of Miami. Dr. Supino is an associate emergency medicine residency program director at Jackson Memorial Hospital.

Wednesday, April 26, 2017


A 53-year-old woman was brought to the ED from a nursing home for hypotension and hypoxia. She appeared septic. Her blood pressure was 80/60 mm Hg, and she was pale, cyanotic, and jaundiced. The patient was nonverbal at baseline due to underlying cerebral palsy, so information about her present illness was provided by her nursing home. Recent records listed elevated alkaline phosphatase and gallstone finding on ultrasound. Physical exam demonstrated abdominal distension and tenderness on palpation of her right upper quadrant.​

Initial workup included CBC, CMP, blood glucose, urinalysis, blood cultures, lactic acid, blood gases, and CT scan of the chest and abdomen/pelvis. The pertinent findings are listed in the table. A left subclavian triple lumen was inserted to administer IV fluids and norepinephrine to correct the hypotension, and she was intubated due to severe hypoxia. Sepsis was treated immediately with broad-spectrum antibiotics (vancomycin and piperacillin/tazobactam), and she was given two units of PRBC to correct the hemoglobin.​

Table. Pertinent Findings from Initial Workup.

Chest CT revealed extensive areas of dense consolidation and nodularity in the right upper and lower lungs, suggesting pneumonia or atelectasis. The abdominal/pelvic CT demonstrated a phlegmon in the gallbladder fossa, which consisted of a bubbly fluid collection measuring 6.5 x 3.7 cm. (Fig. 1.) An ultrasound confirmed a 6 cm echogenic mass containing multiple cystic components, suggestive of a necrotic gallbladder. The common bile duct (CBD) was moderately dilated, measuring 7 mm.

The abdominal/pelvic CT demonstrating a phlegmon in the gallbladder fossa, which consisted of a bubbly fluid collection measuring 6.5 x 3.7 cm.

The patient was admitted to the ICU for ascending cholangitis with septic shock secondary to biliary sources. Urine and blood cultures evidenced bacteriuria and bacteremia with growth of Escherichia coli >100,000 in the urine and Klebsiella pneumonia in the blood. Amikacin was added to the patient's medications, and vancomycin was discontinued. Despite the use of antibiotics, she had persisting leukocytosis with WBC of 23,000.

The patient was scheduled for an exploratory laparoscopy to improve her status and clarify the nature of the biliary problem. She was given 1 unit of PRBC and 3 units of fresh frozen plasma due to prolonged INR before the procedure. It turned into an open surgery when the gallbladder could not be visualized due to the omentum and the right colon. The gallbladder fossa consisted of a large phlegmon and contained several yellowish stones. Surgeons performed a cholecystectomy, right hemicolectomy and ileostomy, and biopsies of the gallbladder and right colon were submitted for pathology. A cholecystectomy tube was inserted into the gallbladder area to drain the fluid. An intraoperative cholangiogram exhibited the passage of dye into the duodenum and equally into the stomach and the distal CBD. Based on the cholangiogram findings, a post-op CT was requested to evaluate possible fistula presence.

Metastasis to the Gallbladder

Gallbladder biopsy revealed infiltrating, poorly differentiated adenocarcinoma with tissue gangrene. Right colon biopsy revealed a Grade 3 tumor in pericolic fat (3 x 1.5 x 0.5 cm) identified as poorly differentiated adenocarcinoma with signet-ring cells and surface ulceration through muscle and serosa. The pathologist's findings indicated a tumor originating from the colon with metastasis to gallbladder. Prognosis at this stage was determined to be poor in light of the local advancement of disease.

Immunohistochemical stains from gallbladder and colon biopsies revealed that both tumors were positive for pancytokeratin, CK20, and CDX2. CDX2 is an intestine-specific transcription factor, which is a specific marker of gastrointestinal adenocarcinomas. The colon tumor was negative for CK7, but the gallbladder tumor revealed scattered CK7-positive cells. Mucicarmine stain visualized intracytoplasmic mucin in the colon tumor, while the gallbladder mucicarmine stain was negative. CEA value was elevated at 6.61.

A CT scan with contrast depicted irregular contrast collection in the gallbladder region, which directly communicated with the duodenum and CBD. (Fig. 2.) Contrast was also visualized within the stomach and small bowel loops. The distal CBD was further dilated, now measuring 10.2 mm. (Fig. 3.) The esophagogastroduodenoscopy confirmed an area on the duodenal wall where there appeared to be a fistula tract (Fig. 4), either cholecystoduodenal or choledochoduodenal fistula, but it could not be definitively identified.

Fig. 2. A CT scan with contrast depicted irregular contrast collection in the gallbladder region, which directly communicated with the duodenum and CBD.

Fig. 3. The distal CBD was further dilated, now measuring 10.2 mm.​

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Fig. 4. The esophagogastroduodenoscopy confirmed an area on the duodenal wall where there appeared to be a fistula tract.​

The patient's family was informed of the diagnosis, and at that time, our patient's mother disclosed that one of her sisters died at 33 from metastatic colon cancer. In considering the patient's comorbidities, mental state, bedbound status, and family history, the physicians involved in her care decided not to pursue any active treatment and transferred her to hospice for palliative care. Sadly, our patient died in hospice one week later.

Colorectal cancer is the third most common cancer worldwide and constitutes a major public health issue globally with an estimated 1.2 million new diagnoses and more than 630,000 cancer deaths per year, amounting to nearly eight percent of all cancer-related fatalities. (Sci Rep 2016;6:29765; World J Gastroenterol 2013;19[41]:7183.) Approximately 56 percent of patients with colorectal cancer die as a result of their cancer. (Sci Rep 2016;6:29765.) Research shows that 20 percent of patients with colorectal cancer have distant metastases at diagnosis, and this figure has remained stable for the past two decades. (Clin Exp Metastasis 2015;32[5]:457; CA Cancer J Clin 2016;66[1]:7.) Colorectal cancer can spread by lymphatic and hematogenous dissemination, as well as by contiguous and transperitoneal routes. The most common metastatic sites are the regional lymph nodes, liver, lungs, and peritoneum. A total of six percent of metastatic adenocarcinomas of unknown primary origin are connected to colorectal carcinoma. (J Clin Oncol 1995;13[8]:2094.)

To our knowledge, this is the first literature report of a middle-aged woman presenting with cholecystitis, gallbladder abscess, and cholecystoenteric fistula, who was subsequently diagnosed with colon adenocarcinoma with metastasis to the gallbladder. Our patient's colon biopsy stained positive for mucicarmine and was also characterized by signet-ring cells. Occasionally, mucin accumulates intracellularly in mucinous adenocarcinomas, resulting in signet-ring cell morphology. (Mod Pathol 2008;21[12]:1533.) Signet-ring histology is associated with dismal prognosis and higher risk of death for colon and rectum cancers, mainly due to delayed diagnosis. (Int Surg 2014;99[6]:691; Ann Surg Oncol 2012;19[9]:2814.)

This was the unfortunate case for our patient who had a peculiar spread of right colon cancer to the gallbladder, with consequent abscess and perforation. A study found that the most common primary tumor that metastasized to the gallbladder is gastric cancer, followed by renal cell carcinoma and hepatocellular carcinoma. (Korean J Radiol 2014;15[3]:334.)

Gallbladder perforations are rare, with reported incidence ranging between two and 10.6 percent in patients with acute cholecystitis and cholelithiasis. (Hepatobiliary Pancreat Dis Int 2009;8[2]:212.) Spontaneous internal biliary fistulas also represent a complication of cholelithiasis in more than 90 percent of cases, and can otherwise be attributed to peptic ulcer disease and malignancy. (Eur Radiol 1999;9[6]:1145; Radiology 2002;224[1]:9.) The most commonly missed opportunity for early diagnosis of colon cancer is the failure to initiate or complete the investigation of iron deficiency anemia. (Br J Surg 1993;80[10]:1327.) Considering that this patient had a family history of colon cancer, she may have benefitted from a more thorough workup because her iron deficiency anemia was from unknown causes.​

Ms. Vesanen is a third-year medical student at the University of Medicine and Health Sciences in St. Kitts. Dr. Raziuddin is an internist and emergency physician at tWeiss Memorial Hospital, Gottlieb Memorial Hospital, and Westlake Hospital, all in Illinois.

Wednesday, April 26, 2017


Infectious processes, such as streptococcal infections, can partially masquerade as alternative diagnosis. Streptococcal infections are a frequent source of infection treated by emergency physicians, and it is crucial that the appropriate tests, antibiotics, and hospitalization are used to recognize rash patterns and to identify causes and the differential of causation.

A 60-year-old woman presented from her primary medical doctor's office with fever, fatigue, tachycardia, and facial discomfort for two days that developed into a malar rash. The patient reported one day of fever, several days of sore throat, and nonproductive cough for several months with new onset pain with swallowing for two days.

Malar distribution rash with tenderness on palpation.

She had no recent travels, known sick contacts, or recent hospitalizations. Initial vital signs included a temperature of 101.9°F, an irregularly irregular heart rate of 120 bpm, a respiratory rate of 18 bpm, a blood pressure of 148/96 mm Hg, and oxygen saturation of 96% on room air. Her physical exam noted posterior oral pharynx erythema with tonsillar exudates, no ocular involvement, clear tympanic membranes, and clear nasal turbinates. A malar distribution rash was noted with tenderness to palpation, inflamed appearance, and clear, raised demarcated edges as shown in the picture. Cardiac exam noted tachycardia and irregularly irregular heart rate without murmur or gallops. Lungs were clear bilaterally. Neurologically she was oriented and alert x3 without meningismus symptoms, and had 5/5 strength in all four extremities.

Her medical history included coronary artery disease with prior ischemic myocardial infarction and percutaneous intervention. She had had coronary artery bypass graft surgery followed by intracardiac defibrillator placement. She also had ischemic cardiomyopathy with congestive heart failure, diabetes, prior deep venous thrombosis on anticoagulation, and chronic foot ulcers with prior lower extremity cellulitis requiring intravenous antibiotics and hospitalization. Her medications included but were not limited to carvedilol, furosemide, rivaroxaban, short- and long-acting insulins, and hydrocodone. She reported allergies to vancomycin and hydromorphone.

Differential consideration included infection, vasculitis, and less likely rheumatologic causes. Laboratory work noted a leukocytosis of 12.5 with an absolute neutrophil count of 10.2. Electrolytes and liver function panel were normal. Rapid strep testing was positive. C-reactive protein was elevated to 2.76 mg/dL, and erythrocyte sedimentation rate was 127. Her antinuclear antibody screen was positive. Chest x-ray was negative for pneumonia, and bedside ultrasound did not demonstrate soft tissue cobblestoning of the face, making cellulitis less likely. The patient was noted to have a normal lactate, but continued to meet severe shock/sepsis criteria after resuscitation. She continued to have tachycardia after two liters of fluid, leukocytes, and fever after acetaminophen and ibuprofen.

Care included 1 g IV ceftriaxone and admission to medical services on telemetry with diagnoses of new onset atrial fibrillation with a rapid ventricular response, sepsis with streptococcal pharyngitis, and presumed erysipelas. Infectious disease and cardiology were consulted by the admitting service.

The patient responded clinically and vitally to antibiotics and intravenous fluids with resolution of atrial fibrillation and sepsis. She was discharged the next day with outpatient antibiotics and follow-up.

Erysipelas and Cellulitis

Recognition of rash patterns remains a mainstay for appropriate and timely treatment of patients in the emergency department. Malar rashes are less common and are frequently a Pavlov's dog response for lupus. Mala (Latin for cheekbone) rashes that are shiny, red, tender, and acute in onset with infectious symptoms are often associated with alternate diagnoses. Streptococcus species are frequent causes for infection and causative for the most diverse set of infectious symptoms. Streptococcus pyogenes, Group A streptococcus, is the most feared of this genus. One unique complication with Group A infections are erysipelas skin changes.

Erysipelas is an acute infection of the upper dermis and superficial lymphatics. The cases are less defined with sharp, raised borders; erysipelas is often confused with cellulitis. Cellulitis is a deeper infection involving skin and soft tissues. (Cutis 1999;64[3]:157; J Cutan Med Surg 1998;2[Suppl 4]:S4; Clin Infect Dis 1996;23[5]:1091.) Historically, the skin changes were often referred to as St. Anthony's fire, and were curable only by an Egyptian monk, St. Anthony. (Am Fam Physician 1995;51[2]:401.) Less commonly, alternate bacterial sources have been identified, including Staphylococcus aureus, Klebsiella pneumonia, Yersinia enterocolitica, and Haemophilus influenzae. (Int J Dermatol 1996;35[11]:779.)

Risk factors for erysipelas include injection drug use, ulcers, wounds, trauma, edema, and surgical procedures involving lymphatics. A facial erysipelas source is most commonly the nasopharynx. (Scand J Infect Dis 1986;18[6]:519; Scand J Infect Dis 1998;30[2]:206.) Erysipelas clinically presents with an abrupt, warm, and tender rash with raised, sharply demarcated, indurated margins. The raised portion is often referred to as perifollicular edema or peau d'orange. (Am J Med 2010;123[5]:414.) The rash is typically rapid with advanced cases demonstrating bullae or vesicles. (J Fam Pract 2010;59[8]:459; J Am Acad Dermatol 1999;41[5 Pt 1]:733.) The lower extremities are more often affected. Facial rashes are typically malar or butterfly patterned. Because the ear does not contain deep dermis tissues, erysipelas, not cellulitis, singularly affects the external ear. (Am J Med 2010;123[5]:414.) Prodromal symptoms include fever, malaise, nausea, chills, and anorexia. Diagnosis is made clinically because aspirations, biopsies, and blood cultures are not sensitive. (Br J Dermatol 1985;112[5]:559.)

The mortality rate is less than one percent in patients receiving appropriate treatment. (Isr Med Assoc J 2001;3[10]:722.) Group A beta-hemolytic streptococcus is the most common agent and is treated with beta-lactams. Penicillin remains the first-line treatment, with penicillin-allergic patients given erythromycin. Outpatient treatment for 10 to 14 days is typically sufficient. (Isr Med Assoc J 2001;3[10]:722; Am J Clin Dermatol 2003;4[3]:157.) Immunocompromised patients and extremes of age usually require a short duration of hospitalization for intravenous antibiotics with continued outpatient therapy. Steroid therapy has been shown to reduce symptom duration and hospital length of stay. (Scand J Infect Dis 1998;30[2]:206.) Clinical improvement begins within 24-48 hours, but some patients have worsening erythema after antibiotic administration due to pathogen destruction and deoxyribonuclease B (DNase B) and hyaluronidase release. (J Fam Pract 2010;59[8]:459.) Antibiotic coverage should be broadened to include penicillinase-resistant penicillin if there is concern for methicillin-resistant Staphylococcus aureus (MRSA) infection. (Am Fam Physician 2002;66[1]:119.)

Dr. Snyder is an emergency physician practicing in northeastern Florida. His medical interests include global health, finance, trauma care, and disaster medicine.

Thursday, April 13, 2017


A 46-year-old man presented to the ED with multiple complaints, including fatigue and dizziness for one day. His primary care physician had diagnosed him with diabetes the previous day, and had prescribed him an oral hypoglycemic as well as insulin. Neither, however, was started at the time of presentation. The patient had a medical history significant for HIV, with his most recent CD4 count above 500, and bilateral sensorineural hearing loss, which had progressively worsened since its initial onset in his 20s. His physical exam was unremarkable except for decreased hearing bilaterally.

A laboratory workup was ordered, including CBC with differential, CMP, blood glucose, β-hydroxybutyrate, and an ECG. Laboratory results were remarkable for a blood glucose level of 593 mg/dl, β-hydroxybutyrate of 7.52 mmol/L, CO2 of 15 mmol/L, and an anion gap of 20, indicating that the patient was suffering from diabetic ketoacidosis. Laboratory results were also significant for a GFR of 33.3 ml/min and creatinine of 2.15 mg/dl, indicating kidney failure. All other results were within normal limits, and his ECG showed no abnormalities.

A thorough family history was taken, and was significant for both diabetes and deafness throughout the patient's maternal side and absent on the paternal side. (Figure.) The patient's brother and mother were deaf and had diabetes, and both were diagnosed before they were 45. His mother's siblings are all affected by at least one pathology. His maternal aunt and uncle were deceased due to stroke and kidney failure, respectively. His maternal grandmother was also affected by diabetes and deafness. His cousins born to maternal uncles were not affected.

The patient was immediately treated with insulin, and was admitted for further investigation and treatment. Due to the patient's strong family history of diabetes, hypoacusis, and pattern of inheritance, a working diagnosis of maternally inherited diabetes and deafness (MIDD) was explored. At the time of admission, the patient was being counseled on genetic testing for confirmation.

An Unrecognized Genetic Disease

MIDD is a distinct subtype of diabetes, caused by a single point mutation in mitochondrial DNA. The mutation most associated with MIDD involves the mtRNALeu(UUR) gene and consists of a 3243A>G transition. (Diabetes 1994;43[6]:746.) It is believed to be part of a spectrum where patients most affected present with MELAS. (Arch Soc Esp Oftalmol 2009;84[7]:360.) As a result of the involvement of mitochondrial DNA, MIDD is inherited by children of all the affected women, while the affected men pose no risk of passing on the mutated genes. (Diabetologia 1996;39[4]:375.)

The syndrome consists of diabetes and sensorineural hearing loss, and may include other organ system manifestations, including ophthalmologic, cardiac, renal, muscular, and neurological pathologies. The organs that are most metabolically active are most commonly involved; they are most affected by deficiencies in mitochondrial-based respiratory oxidation, leading to inefficient cellular energy production. (Diabet Med 2008;25[4]:383.) It is believed that MIDD is responsible for approximately one percent of all diabetic diagnoses. It is, however, often misdiagnosed as Type 1 or 2 diabetes or as Alport syndrome when only deafness and renal symptoms are present. (Diabet Med 2008;25[4]:383.)

The diabetes of MIDD appears to be due to lack of insulin secretion rather than insulin insensitivity. (Ann Intern Med 2001;134[9 Part 1]:721.) The onset of diabetes is usually gradual, with age of onset occurring at 37± 11 years, although up to 20 percent of patients will present acutely and up to eight percent will experience ketoacidosis. (Diabet Med 2008;25[4]:383.)

More than 75 percent of patients will experience sensorineural hypoacusis attributed to the cochlea rather than the cranial nerve. This hearing loss most often presents before the diabetes manifests itself, and is often the only clinical manifestation of the mutation. (Ann Intern Med 2001;134[9_Part_1]:721.)

Associated diseases include end-stage renal failure, myocardiopathies with early heart failure and stroke, muscular abnormalities including biopsies indicating ragged red fibers, characteristic macular retinal dystrophy, and psychiatric disorders such as depression and schizophrenia. (Diabet Med 2008;25[4]:385.)