DR.GAUTAM N. JAINDNB,DCH (Bombay)
Consultant Paediatrician & Neonatologist.Rajasthan Hospitals.
Shahibaug.
CLINICAL PRESENTATIONManav 8 yr Mch
Failure to thrive
Diarrhoea since new born period.
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.
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.
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.
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.
OLD DOCUMENTS
He has been persistently hypoalbumenic.
Tetany :- till date he has almost 2-3 documented episode of tetany which required hospitalization and treatment.
He has been treated by antibiotics and other supportive treatment for diarrhea.
He has been treated for iron deficiency anaemia.
WHERE ARE WE ??
DIFFERENTIAL DIAGNOSIS
Malabsorption with failure to thrive
Coeliac disease.
Milk free diet , Wheat free diet
& coconut oil as coocking oil is been tried unsuccessfully.
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
Abnormal facial featuresLarge 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 spotHe had bilateral pitting oedema.
Systemic examination has been unremarkable except umbilical hernia.
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.
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.
Synopsis of the investigationsRBS 91SGPT 46 -66SGOT 41- 60Sodium – 141, Potassium – 4.3, Chloride – 113.
VBG – N
Stool – Fat globules + ( Oct. 2003)
Searching for the causeUrine for metabolic screening was normal
Urine for MPS screening was normal
Still no clue
TFT – N
UGI scopy – N ,.
Intestinal Biopsy – N ,Tissue transglutaminase – N , Endomyseal antibody – N.
Karyotyping – N.
X-RAY Chest , USG Abdomen , 2-D Echo – N.X-ray Pelvis :- erosion of Gr. Trochanter of Lt. femur.,
Metaphyseal wideningSubchondral sclerosis of both knee.& osteoporosisX-ray wrist :- swelling with fraying metaphyseal
margin,swan neckdeformity of rt. Index,lt. rinf & little finger.
At last… Tandem Mass Spectroscopy :- Suggestive of Methyl
malonic acidemia
Our working diagnosis: ?? Methyl Malonic academia with chronic pancreatitis and malabsorption
Points in favour: Failure to thriveChronic pancreatitis
Points against: No acidosis Dysmorphism.
Methyl malonic acidemiaMethyl 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)
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) gene is on chromosome 6 and 30.Not responsive to vit.B12 therapy.
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.
CLINICAL PRESENTATIONThe 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.
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.
SYMPTOMSDehydration , failure to thrive.Lethargy, muscular hypotonia, floppinessDevelopmental delayFacial dysmorphism (eg, high forehead, broad nasal bridge,
epicanthal folds, long smooth philtrum, triangular mouth)Skin lesions (eg, moniliasis)Occasional hepatomegalyAcute onset of choreoathetosis, dystonia, dysphagia, and
dysarthria (potentially signs of a stroke)Reduced GFR
Laboratory Ketosis , acidosis
Anaemia, neutropenia , thrombocytopenia
Hyperglycinemia , hyperammonemia, hypoglycemia
Presence of large quantities of methylmalonic acid in body fluids.
Diagnosis :-
Measuring mutase activity and by performing complementation study in cultured fibroblast.
Prenatal diagnosis can be done.
Treatment :-Acute attack :-Rehydration.Correction of acidosisProvision of adequate calories.Minimal amounts of protein ( 0.25 g /kg / 24hr).AntibioticsL-Carnitine.Treat Hyperammonemia.Large dose of Vit B12 ( 1-2 mg / 24 hr) instead of biotin.
Treatment :-Long term treatment :- Low-protein diet.L-Carnitine.Vit B12Chronic alkali therapy for pt with low-grade chronic
acidosis.
Prognosis :- depends upon type of enzyme deficiency.Pt. with mutase deff. worse prognosis..
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