1. DR.GAUTAM N. JAIN
DNB,DCH (Bombay)
Consultant Paediatrician & Neonatologist.
Rajasthan Hospitals.
Shahibaug.

2. CLINICAL PRESENTATION
 Manav 8 yr Mch
 Failure to thrive
 Diarrhoea since new born period.

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.

9. WHERE ARE
WE ??

10. DIFFERENTIAL DIAGNOSIS
 Malabsorption with failure to thrive
 Coeliac disease.

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.

14.  Systemic examination has been unremarkable except
umbilical hernia.

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.

17. Synopsis of the investigations
 RBS 91
 SGPT 46 -66
 SGOT 41- 60
 Sodium – 141, Potassium – 4.3, Chloride – 113.
 VBG – N
 Stool – Fat globules + ( Oct. 2003)

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..

34. THAN
K
YOU