MITOCHONDRIAL MYOPATHY WITH RESPIRATORY
MUSCLE INVOLVEMENT
zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA
A C A S E R E P O R T
zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA
J. A. LEVY* ANA M. T S A N A C L I S **
P. A. P. SARAIVA *** CARMEN C. MION ****
PAULO N. B. SALUM****
As from 1956, a series of congenital myopathies benign in character have
been described, the diagnosis of which can only be effected by means of
histo-chemistry and electronic microscopy. Within this group of affections, some are
characterized by alterations in number, form or aspect of striated muscle
mito-chondria
2>
4>
7»
8. In 1971 Engel & col. described a familiar congenital myopathy
involving especially axial and respiratory muscles that presented ultrastructural
alterations of the mitochondria and Z-line
K
The present article concerns a patient with benign congenital myopathy,
except for presenting severe alterations in respiratory muscles.
O B S E R V A T I O N
H.Li., f e m a l e , 10 y e a r s o l d , e x a m i n e d o n J a n u a r y 29, 1979 c o m p l a i n i n g o f difficulty i n w a l k i n g e v e r s i n c e s h e b e g a n t o w a l k at t h e a g e o f 16 m o n t h s , a n d a c r o o k e d s p i n e H e r p a r e n t s s a i d t h a t t h e clinical p i c t u r e w a s s t a t i o n a r y . Familiar antecedents: parents f i r s t c o u s i n , n o r m a l s i s t e r a g e 12. Clinical examination — r a i s e d p a l a t e , t h o r a c i c scoliosis, a n d i n c r e a s e o f l u m b a r l o r d o s i s . Neurological examination — g l o b a l h y p o t o n i a t o a m o d e r a t e d e g r e e , s l i g h t p r o x i m a l m o t o r d e f i c i t in t h e f o u r l i m b s a n d t r u n k . Slight i n v o l v e m e n t o f facial m u s c l e s . Complementary examinations — Spinal X - r a y : rectification c e r v i c a l s p i n e , c o n c a v e d e x t r a l d o r s o - l u m b a r s c o l i o s i s a n d a u g m e n t e d l u m b a r l o r d o s i s . E l e c t r o m y o g r a p h y : c h a r a c t e r i s t i c t r a c e o f p r i m a r y m u s c u l a r lesion. N o r m a l serous e n z y m e s ( C P K , G O T , G P T , L D H ) . M u s c u l a r b i o p s y ( o p t i c a l m i c r o s c o p y ) : alterations c o m p a t i b l e w i t h p r i m a r y m y o p a t h i c p r o c e s s .
W i t h the d i a g n o s i s o f b e n i g n c o n g e n i t a l m y o p a t h y , the p a t i e n t w a s s e n t o n to p h y s i o t h e r a p y . H e r c o n d i t i o n r e m a i n e d u n a l t e r e d u p until the e n d o f 1980 w h e n she b e g a n t o p r e s e n t e p i s o d e s o f c y a n o s i s a n d d r o w s i n e s s s o m e t i m e s a c c o m p a n i e d b y h e a d a c h e s , h a v i n g b e e n on t w o o c c a s i o n s i n t e r n e d in a n i n t e n s i v e c a r e unit, w h e r e
T h i s w o r k w a s c a r r i e d o u t a t the Center f o r I n v e s t i g a t i o n s in N e u r o l o g y o f the N e u r o l o g i c a l Clinic o f S ã o P a u l o U n i v e r s i t y M e d i c a l S c h o o l : * A d j u n c t P r o f e s s o r ; ** A s s i s t a n t P r o f e s s o r , D e p a r t m e n t f o r P a t h o l o g i c a l A n a t o m y ; *** D i r e c t o r , S e r v i c e o f
s h e i m p r o v e d o n l y a f t e r a t r a c h e o s t o m y a n d assisted r e s p i r a t i o n . T h e n e u r o l o g i c a l e x a m i n a t i o n r e m a i n e d unaltered, w i t h t h e e x c e p t i o n of an i n c r e a s e in the d e f i c i e n c y o f r e s p i r a t o r y m u s c l e s that w e r e , b y then, c o n s i d e r a b l y i n v o l v e d . R a d i o s c o p y r e v e a l e d a l m o s t c o m p l e t e a b s e n c e o f d i a p h r a g m m o v e m e n t .
W i t h e l e c t r o n i c m i c r o s c o p y a n a c c u m u l a t i o n o f m i t o c h o n d r i a w a s o b s e r v e d , e s p e c i a l l y in s u b - s a r c o l e m m o u s p o s i t i o n . T h e s e m i t o c h o n d r i a h a d c r e s t s t h i c k e n e d b y material t h a t w a s m o d e r a t e l y e l e c t r o n - d e n s e , s o m e t i m e s a b n o r m a l o n f o r m . A d i s c r e s t d i l a t i o n o f s a r c o m e r a w a s o b s e r v e d in s y s t e m T ( F i g í s . 1 a n d 2 ) .
F o r c e d e x p i r o m e t r y o n t h e p a t i e n t s h o w e d a s e v e r e l y r e s t r i c t e d p u l m o n a r y p i c t u r e r e f l e c t e d in all p a r a m e t e r s ( T a b l e 1 ) . C o m p a r e d t o the s t a n d a r d , vital c a p a c i t y is m u c h d i m i n i s h e d in t h e p a t i e n t ( 3 4 % ) . A n a l y s i s o f f o r c e d r e s p i r a t o r y v o l u m e in t h e f a s t s e g m e n t s u g g e s t e d there is n o c o m p o n e n t t o o b s t r u c t t h e u p p e r r e s p i r a t o r y p a t h w a y s , f o r it w a s d i m i n i s h e d in t h e s a m e p r o p o r t i o n t o vital c a p a c i t y . C o m p a r i n g r e s u l t s in d i f f e r e n t p o s i t i o n s , it c o u l d b e seen that t h e v a l u e s o b s e r v e d i n the d i f f e r e n t d e c u b i t u s p o s i t i o n s a r e m u c h s m a l l e r t h a n t h o s e o b t a i n e d w i t h t h e p a t i e n t in a sitting p o s i t i o n . I n this p o s i t i o n , t h e f o r c e o f g r a v i t y a i d s the m o v e m e n t o f the d i a p h r a g m d o w n w a r d , w h e r e a s in a d e c u b i t u s p o s i t i o n , i t d o e s n o t . I n r i g h t d o r s a l d e c u b i t u s , t h e d i a p h r a g m s e e m s less efficient. B a s e d o n this d a t a , t h e p a t i e n t w a s assisted w i t h m e c h a n i c a l p u l m o n a r y ventilation at n i g h t . A f u r t h e r e x p i r o m e t r y was c a r r i e d o u t a f t e r a p e r i o d o f 26 d a y s .
P r o b a b l y the values s h o w n in this s e c o n d t a b l e ( F V C a n d F E V ) , t h a t i n d i c a t e a
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1 .0l o w e r i n v o l v e m e n t o f t h e r e s p i r a t o r y f u n c t i o n than t h o s e r e f e r r e d t o in T a b l e 1, w e r e the r e s u l t o f r e s t d u r i n g artificial v e n t i l a t i o n ( c a r r i e d o u t at n i g h t ) .
C O M M E N T S
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The patient described by us presented a congenital myopathy relatively
benign by nature and that seemed to keep to stationary symptomatology,
sugges-ting favourable evolution that would allow the patient to lead a practically
normal life. However after the age of 10, severe complications arose that were
characterized by respiratory deficiency, above all because of mal-function of the
diaphragm, which as was natural, worsened in a horizontal position. This picture
was naturally due to an accumulation of C 0
2accompanied by cyanosis, drowsiness
and headache (chronic alveolar hypoventilation).
Only then did the biopsy examination, carried out with electronic microscopy,
permit us to form a diagnosis of mitochondrial myopathy.
With the use of assisted pulmonary ventilation at night and for one or two
hours after lunch, the patient returned to a practically normal life, returning to
school, and carrying on with practically all activities of a child her age. W e
call attention to this extremely important fact that, in cases of diaphragmatic
deficit, even in patients with progressive muscular distrophy (limb girdle form),
in which this deficit is much accentuated, assisted pulmonary ventilation at night
can, as referred by several authors
3>
5>
6, allow these patients regarded as total
invalids to resume a useful life.
S U M M A R Y
A case of a 10-year-old patient with a benign congenital myopathy, suddenly
aggravated because of an accentuated deficit in respiratory muscles is reported.
The institution of assisted respiration at night allowed the patient to return to
her daily activities. Examination of muscular biopsy with ultra-microscope
permitted the diagnosis of mitochondrial myopathy.
R E S U M O
zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA
M iopatia m itocondrial com acom etim ento sev ero da m usculatura respiratória.
R E F E R E N C E S
zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA
1. E N G E L , A . G . ; G O M E Z , M . R . & G R O O V E S , R . V . — A r e c e n t l y r e c o g n i z e d c o n g e n i t a l m y o p a t h y a s s o c i a t e d w i t h m u l t i - f o c a l d e g e n e r a t i o n o f m u s c l e f i b r e s . P r o c . M a y o Clin. 646:666, 1971.
2. J U L I E N , J . ; V A L L A T , J . M . ; V A L L A T , M . & L e B R A N C , M . — O c u l o p h a r y n g e a l m u s c u l a r d y s t r o p h y . J . n e u r o l . Sci. 21:165, 1974.
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4. L U F T , R . ; T K V O S , D . ; P A L M I E R I , G . ; E R N S T E R , L . & A F Z E L M O , B. — A c a s e o f s e v e r e h i p e r m e t a b o l i s m o f n o n - t h y r o i d o r i g i n w i t h a d e f e c t in m a i n t e n a n c e of m i t o c h o n d r i a l r e s p i r a t o r y c o n t r o l . J . clin. I n v e s t . 81:1776, 1982.
5. N E U S T A D T , D . E . ; L E V Y , R . C. & S P I E G E L , I. J . — C a r b o n d i o x i d e n a r c o s i s in a s s o c i a t i o n w i t h m u s c u l a r d y s t r o p h y . J . a m . M e d . A s s o c . 187:616, 1964.
6. N E W S O N - D A V I S , J . — T h e r e s p i r a t o r y s y s t e m i n m u s c u l a r d y s t r o p h y . B r i t . m e d . B u l l . 36:135, 1980.
7. S E N G E R , R . C ; T E R H A A R , B. G . ; T R I J B E L S , J . M . ; W I L L E N S , J . L . ; D A -N I E L S , G. & S T H A D D U D E R S , A . M . — C o n g e n i t a l c a t a r a c t a n d m i t o c h o n d r i a l m y o p a t h y o f skeletal a n d h e a r t m u s c l e a s s o c i a t e d w i t h l a c t i c a c i d o s i s a f t e r e x e r c i s e . J . P e d i a t . 86:873, 1975.
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a b n o r m a l m i t o c h o n d r i a . B r a i n 89:135, 1966.
