Characteristics of intestinal pseudo-obstruction in patients with mitochondrial diseases

Table 1 Criteria for the diagnosis of chronic intestinal pseudo-obstruction

Must include

One or more symptoms of ileus1 onset at least 6 mo prior to diagnosis

One or both of following for the last 12 wk: (1) Abdominal pain; (2) Abdominal bloating

Dilatation and/or air-fluid levels of the intestine on abdominal X-ray, echo and/or computed tomography imaging

No evidence of structural disease (including findings of upper endoscopy, lower endoscopy, computed tomography, barium enema, and small-bowel follow-through) that could explain dilatation and/or air-fluid levels of the intestine

Supportive criteria

Congenital and/or onset under 15 years old must be excluded. Only adult onset is included

Surgical history within the 6 mo prior to diagnosis must be excluded to rule out Ogilvie syndrome, except surgery for CIP

To define CIP at two levels: Primary CIP or secondary CIP. Primary CIP consists of three types: the muscular type, neurogenic type and idiopathic type; Secondary CIP consists of two types: the systemic sclerosis (SSc) type and unclassified type

Family accumulation may exist

Neuropathy such as problems with urination may exist

Some psychosocial disorder may be present

¹Symptoms of ileus include: Abdominal pain, nausea, vomiting, abdominal bloating, abdominal fullness, lack of defecation and/or passing gas. CIP: Chronic intestinal pseudo-obstruction.

Table 2 Age at the oncet of mitochondrial disease and chronic intestinal pseudo-obstruction

Sex	Subclass	Age at the onset of mitochondrial disease, yr	Age at the diagnosis of mitochondrial disease, yr	Age at the diagnosis of CIP, yr
F	MELAS	Difficulty in walking at 40	40	40
M	MELAS	Glucose intolerance at 13	57	46
M	MERRF	Difficulty in walking at 41	50	50
F	CPEO	Palpebral ptosis at 71	81	-
F	MELAS	Impaired hearing at 45	54	-
M	MELAS	Impaired hearing at 24	29	-
M	CPEO	Palpebral ptosis at 40	69	-
F	CPEO	Impaired eye movement at 30	52	-
F	MELAS	Impaired hearing at 25	40	43
M	CPEO	Palpebral ptosis at 49	49	-
F	MERRF	Muscular weakness at 46	54	-
M	MELAS	Impaired hearing at 47	52	-
M	MELAS	Epilepsy at 11	18	-
M	CPEO	Glucose intolerance at 40	67	-
M	MELAS	Impaired hearing at 24	31	-
F	MELAS	Impaired hearing at 12	17	25
F	MELAS	Impaired hearing at 54	60	-
F	MELAS	Epilepsy at 40	44	-
M	MELAS	Glucose intolerance and impaired hearing at 18	18	-
F	MELAS	-	23	-
F	MELAS	Chronic diarrhea at 26	40	-1
F	MELAS	Epilepsy at 18	18	26
F	MELAS	Difficulty in walking and hearing at 63	69	69
F	MELAS	Glucose intolerance at 33	42	55
M	CPEO	Palpebral ptosis at 16	44	-
M	MELAS	Epilepsy at 29	29	-
F	CPEO	Palpebral ptosis at 13	17	-
F	CPEO	Palpebral ptosis at 59	59	-
M	MELAS	Epilepsy at 21	21	34
F	MELAS	Glucose intolerance at 46	48	-
F	MERRF	Difficulty in walking at 20	50	-

¹This patient died of uncontrolled epilepsy and aspiration pneumonia 5 mo after the onset of intestinal pseudo-obstruction and did not fulfill the diagnostic criteria. M: Male; F: Female; CIP: Chronic intestinal pseudo-obstruction; MERRF: Myoclonus epilepsy associated with ragged-red fibers; MELAS: Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes; CPEO: Chronic progressive external ophthalmoplegia.

Table 3 Characteristics of chronic intestinal pseudo-obstruction in patients with mitochondrial diseases

Sex	Subclass	Type of abdominal discomfort	Area of dilated intestine	Treatment
F	MELAS	Nausea, vomiting, diarrhea, constipation	Small intestine	PEG, neostigmine
M	MELAS	Diarrhea	Small intestine	Antidiarrheal drug
M	MERRF	Pain, diarrhea, distension	Small and large intestines	Mosapride, dimethicone, antiflatulent, daikenchuto, pantothenic acid
F	MELAS	Diarrhea, constipation, distension	Small and large intestines	Mosapride, daikenchuto, magnesium oxide
F	MELAS	Nausea, vomiting, diarrhea, constipation, pain	Small intestine	PEG, antiflatulent, magnesium oxide, antidiarrheal drug
F	MELAS	Nausea, vomiting, constipation, pain	Small intestine	Prostarmon, magnesium oxide, dimethicone, daikenchuto, mosapride, neostigmine, sodium picosulfate hydrate
F	MELAS	Nausea, vomiting, distension	Small intestine	Magnesium oxide, daikenchuto
F	MELAS	Nausea, vomiting	Large intestine	Daikenchuto, sennoside
M	MELAS	Nausea, vomiting, diarrhea, distension	Small intestine	Daikenchuto, mosapride, magnesium oxide, lansoprazole, neostigmine, dimechicone

M: Male; F: Female; CIP: Chronic intestinal pseudo-obstruction; MERRF: Myoclonus epilepsy associated with ragged-red fibers; MELAS: Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes; PEG: Polyethylene glycol.

Table 4 Characteristics of chronic intestinal pseudo-obstruction in patients with progressive muscular dystrophy

Subclass	No. of patients	No. of females	Age at the onset1	Age at the diagnosis1
Duchenne muscular dystrophy	2	0	1	2 (1-3)
Becker muscular dystrophy	7	0	10 (1-30)	19 (6-43)
Limb-girdle muscular dystrophy	4	1	22.5 (5-40)	49 (10-53)
Facio-scapulo-humeral muscular dystrophy	1	1	NS	NS
Myotonic dystrophy	38	18	30 (5-62)	39 (12-67)
Total	52	20	25 (1-62)	34.5 (1-67)

¹Data is presented as median age (range). NS: Not stated. None of the patients with progressive muscular dystrophy in this study fulfilled the diagnostic criteria of chronic intestinal pseudo-obstruction.