| Revised: 28 February 2019 | Accepted: 17 March 2019

DOI: 10.1111/1756-185X.13575

APLAR GRAND ROUND CASE

Case study of an inborn error manifested in the elderly: A
woman with adult‐onset mitochondrial disease mimicking
systemic vasculitis
Jae Hyun Lee1

| Min Jung Kim2 | Sung‐Hye Park3 | Jong‐Hee Chae4 | Kichul Shin5

1
Department of Internal Medicine, Seoul
National University Hospital, Seoul National
University College of Medicine, Seoul, Korea
2

Abstract
Mitochondrial diseases are a group of disorders presenting mainly during infancy due

Division of Rheumatology, Seoul National
University Hospital, Seoul National
University College of Medicine, Seoul, Korea

to pathological dysfunction of the mitochondrial respiratory chain. We report a case

3

69‐year‐old woman was admitted due to fatigue, general weakness, and a drowsy

Department of Pathology, Seoul National
University Hospital, Seoul National
University College of Medicine, Seoul, Korea
4
Department of Pediatrics, Seoul National
University Children’s Hospital, Seoul
National University College of Medicine,
Seoul, Korea
5

Division of Rheumatology, Seoul
Metropolitan Government‐Seoul National
University Boramae Medical Center, Seoul,
Korea
Correspondence
Kichul Shin, Division of Rheumatology,
SMG‐SNU Boramae Medical Center, Seoul,
Korea.
Email: [email-masked]

of mitochondrial disease in an elderly woman complaining of generalized myalgia. A
mental status. A brain magnetic resonance imaging (MRI) demonstrated multifocal
lesions of increased T2 signal intensity, and laboratory findings were consistent with
Fanconi syndrome. During her hospital course, she developed seizures, stress‐in‐
duced cardiomyopathy, and respiratory failure. A muscle biopsy demonstrated rag‐
ged‐red fibers in the muscle tissues seen in mitochondrial myopathy. We confirmed
an 8 kb deletion in her mitochondrial DNA. Following treatment with l‐carnitine, co‐
enzyme Q10, and supportive measures, brain lesions on MRI scans disappeared, and
the general symptoms gradually improved.
KEYWORDS

Fanconi syndrome, MELAS, mitochondrial myopathy

1 | I NTRO D U C TI O N

2 | C A S E R E P O RT

A pathological dysfunction of the mitochondrial respiratory chain

A 69‐year‐old woman visited the emergency department with a 2‐

can lead to mitochondrial disease. Many of these disorders manifest

day history of high fever and somnolence. The patient was previously

clinically during infancy because they involve organ systems relying

healthy, except for hyperlipidemia and a benign gastric intraepithe‐

highly on aerobic metabolism, such as the central nervous system

lial tumor diagnosed 10 years earlier. A month prior to admission,

(CNS), heart, and skeletal muscles.1 In fact, respiratory chain defi‐

the patient was briefly hospitalized with a 4‐month history of severe

ciencies may generate almost any symptom, in any organ system, at

myalgia involving her shoulders and thighs, along with general weak‐

any stage of life. When the musculoskeletal system is involved, it is

ness and a mild fever (up to 37.5°C). At the time, other findings in

called “mitochondrial myopathy,” regardless of whether myopathy is

the physical exam were unremarkable. Among the laboratory find‐

the main clinical manifestation or a minor symptom. The range of

ings, only mild hyponatremia (127 mmol/L) was present; however,

skeletal muscle involvement varies widely: a subclinical manifesta‐

it was soon resolved with water restriction. She was diagnosed

tion, a mere elevation of serum creatinine kinase, or a morbid weak‐

with fibromyalgia in accordance with the 1990 American College of

ness of muscle groups, and muscle cramps. 2 Here we report a case

Rheumatology classification criteria and was prescribed a tricyclic

of mitochondrial disease in an elderly woman presenting with gener‐

antidepressant (TCA) and tramadol. However, her myalgia did not

alized myalgia.

improve with medication or exercise. Two weeks prior to admission,

Int J Rheum Dis. 2019;1–5.

wileyonlinelibrary.com/journal/apl 
© 2019 Asia Pacific League of Associations for
Rheumatology and John Wiley & Sons Australia, Ltd

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LEE et al.

she had developed general weakness and fatigue, followed by som‐

regarding her chest, abdomen, and joints were unremarkable. The

nolence. On the day of her visit to the hospital, her consciousness

neurological examination revealed an intact pupil response, corneal

rapidly deteriorated over several hours.

and gag reflexes, and diminished motor strength: 2/5 in the bilat‐

The patient was an Asian woman measuring 148 cm in height.

eral upper extremities and 4/5 in the bilateral lower extremities.

Her initial vital signs were: blood pressure, 149/84 mm Hg; pulse

Deep tendon reflexes were intact. Initial laboratory test results

rate, 135 beats/min; respiratory rate, 40/min; body temperature,

are depicted in Table 1. Anti‐nuclear antibodies, rheumatoid factor,

39°C; and O2 saturation, 96% at room temperature. She had stupor,

complement levels, erythrocyte sedimentation rate, and C‐reactive

with a Glasgow Coma Scale of E3V2M5. The physical examination

protein were all negative or within normal limits. The chest X‐ray

revealed chemosis and livedo reticularis in her extremities. Findings

revealed no abnormal lesions. A brain magnetic resonance imaging

TA B L E 1

Laboratory findings

Laboratory test

Initial

1 month later

Reference range

Arterial blood gas analysis
pH

7.343

7.456

pCO2 (mm Hg)

26.9

28.7

pO2 (mm Hg)

108

96.9

HCO3 (mmol/L)

16.6

21.9

SaO2 (%)

98.3

98.1

Complete blood cell
White blood cell (/µL)
Hemoglobin (g/dL)
Platelet (/µL)

13 250
13.1

9110
9.3

225 000

339 000

1027

4000 – 10 000
12 ‐ 16
130 000 ‐ 400 000

Muscle enzyme
Creatinine kinase (IU/L)

57

20 ‐ 270

Creatine kinase MB
fraction (ng/mL)

4.5

6.4

0 ‐ 6.6

Troponin I (ng/mL)

0.63

0.16

0 ‐ 0.028

Serum
Sodium (mmol/L)
Potassium (mmol/L)

133
2.9

137
4.0

135 ‐ 145
3.5 ‐ 5.5

Chloride (mmol/L)

109

106

98 ‐ 110

Total CO2 (mmol/L)

13

19

24 ‐ 31

Phosphorus (mg/dL)

1.6

3.9

2.5 ‐ 4.5

Calcium (mg/dL)

7.5

8.4

8.8 ‐ 10.5

Glucose (mg/dL)

238

120

70 ‐ 110

Blood urea nitrogen
(mg/dL)

16

5

10 ‐ 26

Uric acid (mg/dL)

2.3

1.6

3.0 ‐ 7.0

Total protein (mg/dL)

4.7

5.3

6.0 ‐ 8.0

Albumin (g/dL)

2.9

3.0

3.3 ‐ 5.2

Creatinine (mg/dL)

0.6

0.5

0.7 ‐ 1.4

Lactic acid (mmol/L)

3.3

1.3

0.7 ‐ 2.5

24‐h urine
Sodium (mmol/d)

390

112

40 ‐ 220

Potassium (mmol/d)

196

101

25 ‐ 120

Chloride (mmol/d)

393

106

110 ‐ 250

Calcium (mg/d)

321

167

70 ‐ 180

Phosphate (g/d)

4.3

Glucose (g/d)

103.0

Protein (mg/d)

3899

1.6

0.4 ‐ 1.3

—

0.5 ‐ 1.5

448

1 ‐ 114

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LEE et al.

F I G U R E 1 (A) Brain magnetic
resonance imaging (MRI) at the time of
admission. Note increased signal intensity
in the pons and basal ganglia (arrows, T2‐
weighted image). (B) Brain MRI 1 mo later.
The abnormal lesions seen before are
diminished (arrows, T2‐weighted image)

(A)

(B)

(MRI) (Figure 1A) revealed multifocal lesions in the pons, both tem‐

3 | D I S CU S S I O N

poral lobes, basal ganglia, right subcortical area, and the occipital
lobe. The cerebrospinal fluid analysis was within normal limits.

This case represents a rare diagnosis of adult‐onset mitochondrial

The patient was transferred to the intensive care unit on hos‐

disease, which initially manifested as severe myalgia and mild fever,

pital day 2 (HD 2) after her level of consciousness further deterio‐

followed by altered mentality, high fever, and dyspnea. Even though

rated and tachypnea worsened. A working diagnosis of neuroleptic

it is caused by an inherited genetic disorder, mitochondrial myopathy

malignant syndrome or CNS vasculitis including Behcet's disease,

can occur during early‐to‐middle adulthood.3 In adults over 40 years

polyarteritis nodosa, and primary CNS vasculitis was made. The

of age, the condition shows chronic and slowly progressive muscle

patient was administered intravenous methylprednisolone (1 g)

involvement, whereas in young patients it is usually multi‐systemic

for 3 days. On HD 6, her serum creatine kinase levels began to

and exhibits a life‐threatening progressive course.4 Elderly patients

rise, and a biopsy of both gastrocnemius muscles was performed.

usually complain of myalgia as well as fatigue, 2,4 which cannot be dis‐

Surprisingly, ragged‐red fibers were detected under light micros‐

tinguished easily from fibromyalgia and chronic fatigue syndrome.

copy, and electron microscopy revealed subsarcolemmal clusters

Indeed, a few patients who were initially suspected as having fibro‐

of mitochondria, which contained paracrystalline inclusion bod‐

myalgia were finally diagnosed with mitochondrial myopathy based

ies (Figure 2). These findings led to the diagnosis of mitochondrial

on muscle biopsy.5-7 However, other cases merely presented with

myopathy. Furthermore, gene studies involving muscle specimens

musculoskeletal symptoms, unlike our case, which was associated

revealed an 8 kb deletion in the patient's mitochondrial DNA

with profound systemic involvement.

(Figure 3). With supportive care including prednisolone, oral l‐car‐

While seizures or stroke‐like episodes appear in later stages of

nitine, and coenzyme Q10, in addition to extensive rehabilitation,

mitochondrial myopathy, symptoms such as hearing loss usually ap‐

the patient fully recovered after a 2‐month period and was dis‐

pear earlier in the disease course. However, this patient did not show

charged. A follow‐up brain MRI revealed a substantial decrease in

any symptoms or signs until she first visited the hospital with severe

the aforementioned lesions (Figure 1B).

myalgia. The symptoms and signs of mitochondrial disease may have

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LEE et al.

(A)

F I G U R E 2 Biopsy specimen from
gastrocnemius muscle. (A) “Ragged‐
red fibers” (arrows, modified Gomori
trichrome stain, 400×). (B) Electron
microscopy findings of parking lot
inclusions in the mitochondria

(B)

F I G U R E 3 Results of mitochondrial DNA polymerase chain reaction of 3 normal controls (NC, left 3 lanes) and the present case (4th lane)
showing a large single deletion (about 8 kb) in mitochondrial DNA of the patient
been triggered by medications such as TCA and tramadol. There is

delayed onset of symptoms occurring later in life. Therefore, vasculi‐

a case report of a young patient with multisystem failure in which

tis or infections associated with multiple etiologies were first consid‐

there was suspected temporary mitochondrial dysfunction after an

ered or suspected in previous cases of CNS involving mitochondrial

overdosage of TCA.

8

myopathy.1,10

CNS manifestations of mitochondrial disease vary according

In our case, during her worst stage of illness, the patient showed

to the disease subtypes, including atypical migraine, dementia,

an electrolyte imbalance and a high lactic acid level, consistent with

seizures, ataxia and movement disorders, stroke‐like episodes,

Fanconi syndrome. Although the kidney is one of the most frequently

1,9

In our case, CNS vasculitis was

involved organs in mitochondrial disease, Fanconi syndrome is not

first suspected rather than a mitochondrial disease because of the

a common accompaniment in patients diagnosed with adult‐onset

and even loss of consciousness.

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LEE et al.

mitochondrial disease. When mitochondrial diseases involve kidneys,
children tend to present with proximal tubulopathy at an early age, as
part of a multi‐organ disease, mostly leading to a poor prognosis. By
contrast, in adults the condition tends to mimic a focal segmental glo‐
merulosclerosis‐like feature with a milder phenotype.1,11 Overall, severe
clinical manifestations are rare in elderly patients with mitochondrial
disease. Approximately 70% of patients with MELAS (mitochondrial
encephalomyopathy, lactic acidosis, and stroke‐like episodes), which is
one of the most severe forms of mitochondrial diseases, are known to
present with initial symptoms between 2 and 20 years of age.12
Clinical manifestations in our case were not consistent with
large‐scale mitochondrial DNA (mtDNA) deletions, such as Kearns‐
Sayre syndrome, progressive external ophthalmoplegia, Pearson
syndrome, or age‐related skeletal muscle and hepatic dysfunction.3
However, the clinical expression of mitochondrial disease is exceed‐
ingly variable even in those carrying the same mtDNA mutation.
Moreover, heteroplasmy, which refers to random differences in the
ratio of mutant to normal mtDNA in target tissues during embryo‐
genesis, is a very distinctive feature of mtDNA, and triggers the di‐
verse manifestations of mitochondrial disease.3 Heteroplasmy may
have contributed to the slow progress of our patient with devastat‐
ing clinical presentation.
Treatment for mitochondrial diseases mainly consists of symp‐
tomatic management of the diverse manifestations. Until now, no
clear evidence supported interventions in mitochondrial disorders.13
However, small case study reports have suggested a few effective
treatments for mitochondrial myopathy. These include respiratory
chain cofactors, such as coenzyme Q10, antioxidants, and replenish‐
ment of the deficient biochemicals such as l‐carnitine.14 Our patient
was prescribed prednisolone, coenzyme Q10, and l‐carnitine, as rec‐
ommended in previous studies.
In summary, this case exemplifies that mitochondrial disease in
an elderly patient may present with generalized myalgia, constitu‐
tional symptoms, and clinical features of CNS and/or renal tubular

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defects. In such cases, a muscle biopsy could facilitate the diagnosis
of mitochondrial myopathy.

How to cite this article: Lee JH, Kim MJ, Park S‐H, Chae J‐H,
Shin K. Case study of an inborn error manifested in the
elderly: A woman with adult‐onset mitochondrial disease

ORCID
Jae Hyun Lee
Kichul Shin

https://orcid.org/0000-0002-5668-4793
https://orcid.org/0000-0002-6749-7598

mimicking systemic vasculitis. Int J Rheum Dis. 2019;00:1–5.
https://doi.org/10.1111/1756-185X.13575