3. He is second child of the non-consanguineous parents.
FTND(05-07-2003) with Bth Wt 2.8kg.
First sib is normal.
No significant ante-natal event.
4. He was on top feed since birth because he did not suck
initially.
He lost almost 1 kg wt. during first mth of age for
persistent diarrhea.
Since then he has intermittent diarrhea till date.
Motion is non-bloody, large bulky, foul smelling & non-
greasy.
Usually not been associated with vomiting and fever.
It never happens in summer season when he is eating
only Mango & Roti.
5. There is no h/o polyurea and polydypsia.
No h/o Jaundice in past.
No h/o suggestive of cardiac ds.
No h/o recurrent tonsillitis & Adenoids.
6. CAUSES OF FAILURE TO THRIVE
Birth to 3 mth- perinatal infection,GER,IEM,Cystic
fibrosis.
3 – 6 mth - HIV, GER,IEM,Milk protein
intolerance,cystic fibrosis,RTA.
7 – 12 mth - Improper weaning, GER, RTA.
12 + mth - GER , Tuberculosis , chronic disease.
7. OLD DOCUMENTS
He has been persistently hypoalbumenic.
Tetany :- till date he has almost 2-3 documented episode
of tetany which required hospitalization and treatment.
8. He has been treated by antibiotics and other supportive
treatment for diarrhea.
He has been treated for iron deficiency anaemia.
11. Milk free diet , Wheat free
diet
&
coconut oil as coocking oil
is been tried
unsuccessfully.
12. ON EXAMINATION
Short statured.
normal vital (T-n, HR 100/ min & BP 80/60 mm hg).
Wt. 15 kg ( 24kg) , Hc 47 cm, Ht. 104.5 cm (126 cm). LS
54.5cm
13. Abnormal facial features
Large forehead, synorphis, Hypertelorism,
flat bridge of nose, low set ears with abnormal pinna,
Epicanthic fold, high arch palate.
Single palmer crease, clinodactyly.
Oedematous dorsum of Rt. Hand & lt. foot.
Scoliosis, café-au-lait spot
He had bilateral pitting oedema.
15. Synopsis of the investigations
( 2007) Hb. 5.7 gm% , Retic ct. 2.27%, Hb. Electrophoresis
– N. Iron
studies suggestive of iron deficiency (Treated with iron
and good
response)
(2012) Hb. 13.9gm%, Tc 8700 , N73, L14, Plt. Ct.
2,90,000.
16. Synopsis of the investigations
2003 2008 -12
Cal. 11.6 5.2 – 7.8
Phosphorus 6.9 4.6
Albumin 1.7 – 2
PTH - 234 185.
18. Searching for the cause
Urine for metabolic screening was normal
Urine for MPS screening was normal
19. Still no clue
TFT – N
UGI scopy – N ,.
Intestinal Biopsy – N ,Tissue transglutaminase – N ,
Endomyseal antibody – N.
Karyotyping – N.
20. X-RAY Chest , USG Abdomen , 2-D Echo – N.
X-ray Pelvis :- erosion of Gr. Trochanter of Lt. femur.,
Metaphyseal widening
Subchondral sclerosis of both knee.& osteoporosis
X-ray wrist :- swelling with fraying metaphyseal
margin,swan neckdeformity of rt. Index,lt. rinf & little
finger.
21. At last…
Tandem Mass Spectroscopy :- Suggestive of Methyl
malonic acidemia
22. Our working diagnosis: ?? Methyl Malonic academia
with chronic pancreatitis and malabsorption
Points in favour:
Failureto thrive
Chronic pancreatitis
Points against: No acidosis
Dysmorphism.
23. Methyl malonic acidemia
Methyl malonic acid is derived from propionic acid as part of
the catabolic pathways of isoleucine, valine, threonin,
methionine, cholesterol, and odd-chain fatty acids.
Isoleucine, valine, threonin, methionone, cholesterole,and
odd chain fatty acids
↓
Propionic acid → methyl malonic acid → Succinic
acid
↑
methylmalonyl CoA racemase
methylmalonyl CoA mutase ( coenzyme- adenosylcobalamin )
Defects in the intracellular metabolism of vit B12 ( cobalamin)
24. Defficiency of either mutase or its coenzyme causes an
accumulation of methylmalonic acid and its precursors in
body fluids.
Defficiency of racemase has not been confirmed.
Methylmalonyl CoA mutase (50%) &
Adenosylcobalamin (50%)
/
/
mut° mut¯
( no detectable enz.activity) ( residual enz. Activity)
25. Defects in the intracellular metabolism of vit B12 –
At least 7 different defects been identified designated as
cbl A through G.
A subset of children with defects of intracellular
cobalamin metabolism may also have simultaneous
homocystinuria.
In addition, transient MMA can be detected in otherwise
healthy infants.
26. CLINICAL PRESENTATION
The mut° and mut¯ forms of MMA typically present
during the newborn period and early infancy,
respectively.
CblA, cblB, cblC, and cblH forms of MMA typically
present during early infancy.
MMA forms CblD and cblF typically present during later
infancy or childhood.
The cblC form of MMA may present during childhood or
adolescence.
27. HISTORY :-
A history of poor feeding, vomiting, progressive lethargy,
floppiness, and muscular hypotonia in a newborn who
has been healthy for the first 1-2 weeks of life Is typical
for methylmalonic academia (MMA) mut° or MMA mut-.
Older infants or children with one of the other forms of
MMA or mild mut- may present for the first time during
an episode of decompensation with lethargy, seizures,
and hypoglycemia.
28. SYMPTOMS
Dehydration , failure to thrive.
Lethargy, muscular hypotonia, floppiness
Developmental delay
Facial dysmorphism (eg, high forehead, broad nasal bridge,
epicanthal folds, long smooth philtrum, triangular mouth)
Skin lesions (eg, moniliasis)
Occasional hepatomegaly
Acute onset of choreoathetosis, dystonia, dysphagia, and
dysarthria (potentially signs of a stroke)
Reduced GFR
29. Laboratory
Ketosis , acidosis
Anaemia, neutropenia , thrombocytopenia
Hyperglycinemia , hyperammonemia, hypoglycemia
Presence of large quantities of methylmalonic acid in
body fluids.
30. Diagnosis :-
Measuring mutase activity and by performing
complementation study in cultured fibroblast.
Prenatal diagnosis can be done.
31. Treatment :-
Acute attack :-
Rehydration.
Correction of acidosis
Provision of adequate calories.
Minimal amounts of protein ( 0.25 g /kg / 24hr).
Antibiotics
L-Carnitine.
Treat Hyperammonemia.
Large dose of Vit B12 ( 1-2 mg / 24 hr) instead of biotin.
32. Treatment :-
Long term treatment :-
Low-protein diet.
L-Carnitine.
Vit B12
Chronic alkali therapy for pt with low-grade chronic
acidosis.
33. Prognosis :-
depends upon type of enzyme deficiency.
Pt. with mutase deff. worse prognosis..
